Sir Henry Dale Fellowships: people we've funded

This list includes current and past grantholders.

2018

Dr Niwa Ali

King's College London

Elucidating how tissue resident regulatory T cells contribute to epithelial stem cell homeostasis and tissue regeneration

The maintenance of tissue homeostasis is dependent upon the immune cells present in that tissue, but also the ability of stem cells (SCs) to renew themselves. How immune cells influence the function of SCs is largely unknown. The skin contains immune cells known as regulatory T-cells (Tregs). Conventionally, these cells act by suppressing over-activated immune cells in the tissue. We have recently shown that Tregs in the skin are required for the efficient function of skin SCs, and they exert their function via expression of a receptor, called Jagged-1 (Jag1). We will dissect how Jag1-expressing Tregs influence skin SCs during normal skin function and during skin cancer.

By understanding how Jag1 and Tregs work in tissues, we can better understand how SC- mediated diseases and cancer progression occurs and we can develop better targeted therapies for these diseases.

Dr Elizabeth Ballou

University of Birmingham

Sense and respond: investigating molecular mechanisms regulating Cryptococcus neoformans titan cell formation in response to bacterial triggers

Microscopic fungi are an under-appreciated cause of infection and death in patients worldwide. It is estimated that 1.5 million people die from fungal infections each year, which is comparable to the number of deaths from malaria. One of the most important fungi is Cryptococcus neoformans, which grows in the lung and escapes our immune defences, infecting the brain and causing meningitis. One way that Cryptococcus escapes immune cells is by extreme changes in cell size. So-called titan cells are much larger than immune cells and can survive immune attack, making them important to treatment strategies. But how these cells form is largely unknown.

I showed that titan cells form when Cryptococcus interacts with bacteria that normally grow in our lungs as part of our healthy microbiome. My research will address how bacteria trigger Cryptococcus to make titan cells, how Cryptococcus detects the presence of bacteria in its environment, and how Cryptococcus changes size to cause disease.

My findings will be used during the development of treatment strategies for fungal infections.

Dr Anna Barnard

Imperial College London

Targeting protein-protein interactions in Salmonella persisters: an innovative approach to tackling recurrent infections

Bacterial resistance to antibiotics is one of the biggest challenges facing the modern world. One way in which bacteria survive in the presence of antibiotics is to generate small populations of non-growing cells called persisters. This process is triggered by proteins called toxins whose activities are tightly controlled by antitoxin proteins. In the presence of an environmental stimulus, such as an antibiotic, the antitoxin is degraded allowing the toxin to initiate a dormant, antibiotic-tolerant persister state. Once this external stimulus is removed, the bacteria can return to its original prolific state resulting in the recurrence of infections such as typhoid and tuberculosis which affect thousands of people worldwide each year.

I aim to reverse the formation of persisters in bacteria and restore their sensitivity to antibiotics. I will do this by making molecules which mimic the natural activity of antitoxin proteins.

My findings will help us understand more about antibacterial resistance and develop ways to reverse it.

Dr Alexander Borodavka

Imperial College London

Uncovering the roles of dynamic RNA interactions during assembly and assortment of multi-segmented viral genomes

Rotaviruses are highly contagious viruses that infect children, causing more than 200,000 deaths worldwide each year, mostly in low-income countries. It is essential to understand the molecular make up of rotaviruses if we are to develop new treatments to fight them. A single infectious rotavirus particle contains 11 unique RNA segments used to store its genetic material, serving as a multi-page instruction manual for building new viruses. It is a mystery how rotaviruses select and package the distinct segments, ensuring that each newly built virus has a complete set of instructions for infecting cells.

I will use a combination of sensitive microscopy and molecular biology tools to crack the code of how rotaviruses select and package a complete set of their RNA segments. 

Understanding the mechanism of segment counting will help us design improved vaccines that offer greater protection against rotaviruses and identify new targets for developing antiviral drugs.

Dr Daniel Bose

University of Sheffield

Dissecting the molecular basis of eRNA function

Enhancers are regulatory DNA sequences that control when and in what tissue genes are turned on and off. Only a small amount of the genome contains genes, but much of the genome is transcribed into RNA; thus many RNAs do not code for proteins. I will focus on  enhancer RNAs (eRNAs) which are important for turning genes on and off, but it is unclear how they do this.

I will investigate the way eRNAs work. I will look at how they fold up to form different shapes and how this changes the activity of the proteins that turn genes on and off. I will do this in vitro and in cells, looking across the genome. I will also look at the atomic details of how folded eRNAs interact with regulatory proteins.

My research will uncover mechanisms that describe how eRNAs work.

Dr Benjamin Brennan

University of Glasgow

What makes phleboviruses tick? Examining the molecular interactions of tick-borne phleboviruses with their arthropod vector

Ticks feed on the blood of multiple host species including humans which has enabled them to transmit many diseases, and cases of tick-borne diseases have been rising at an alarming rate. Despite this increase, we still do not fully understand how ticks transmit disease nor how arboviruses interact with ticks. One emerging arbovirus is the bunyavirus called SFTS phlebovirus (SFTSV).

I will use molecular tools to explore how tick-borne phleboviruses interact and modulate the immune system of ticks to spread to mammalian hosts. I will also investigate whether virus particles that originate from tick cells can induce more severe disease symptoms in mammalian hosts than those originating from mammalian cells.

My findings will increase our understanding of how arboviruses interact with ticks and how this interaction influences disease transmission.

Dr Alex Clarke

University of Cambridge

The neural dynamics of how expectation modulates visual object recognition

How do we understand what we see? The way we recognise objects depends on dynamic transformations of information from vision to semantics. Our understanding of what we see is shaped by the environment. When we see an object, we are already in a complex and rich environment and this leads to expectations about the things we are likely to see.

My proposed research will test how the environment changes the dynamics of visual and semantic activity in the brain. I will combine lab-based and real-world studies using a multimodal brain imaging framework using fMRI, MEG, EEG and mobile EEG, with emerging methodologies including augmented reality, computational modelling, multivariate analyses, neural oscillations and brain connectivity.

This research will advance models of object recognition, which currently have little to say on the dynamic neural mechanisms of how the world interacts with our perception of objects.

Dr Gideon Coster

Institute of Cancer Research

Replication through structure-prone DNA – mechanism and impact on genome stability

Each dividing cell in our body must produce two accurate copies of its genome. Certain regions of the genome are more difficult to copy than others, with repetitive sequences being especially challenging. Genetic alterations within repetitions often occur in cancer and give rise to heritable disorders such as fragile X syndrome. It is therefore important to understand how repeats are copied accurately in normal cells and how this goes wrong in disease.

I want to understand how replication deals with repetitive sequences. I will recreate the entire process of DNA replication in a test tube. I will identify the factors that are required to prevent replication errors and reveal how they work.

My results will provide insight into the process of DNA replication and may improve our understanding, diagnosis and treatment of diseases such as fragile X syndrome and cancer.

Dr Tiago Cunha Luis

Imperial College London

Role of the haematopoietic stem cell niche in pre-leukaemic clonal haematopoiesis and myelodysplatic syndromes

Haematopoietic stem cells (HSC) sustain the production of blood cells and are located in the bone marrow, where other cell types, known as the niche, support and regulate their function. Mutations of HSCs are associated with myelodysplastic syndromes (MDS) and pre-leukaemic conditions. The mutations have a competitive advantage over healthy HSCs. MDS is characterised by the accumulation of dysfunctional HSCs, inefficient production of blood cells and a higher risk to developing leukaemia. There are currently no effective treatments for MDS. MDS-HSCs are highly dependent on the niche where they reside but it is still largely unknown exactly how.

Targeting the MDS-HSC niche constitutes a novel and unexplored therapeutic avenue. I will identify the niche and the mechanisms by which it confers advantage to MDS-HSCs.

My findings will lead to the design of new therapies for MDS.

Dr Clarissa Czekster

University of St Andrews

Divide and conquer: disrupting bacterial biofilms with cyclic dipeptides

By 2050, someone will die from antibiotic-resistant bacterial infections every three seconds. We need to develop new drugs to combat antibiotic resistance. Many bacteria grow by sticking to a surface in structures called biofilms. Some bacteria are completely resistant to antibiotics when they are part of a biofilm. Cyclic dipeptides are molecules that can disrupt bacterial growth and biofilm formation. They are common in nature but their biological function is unknown.

I will study the enzymes that make these molecules, how they are affecting bacteria and how this information can be used to our benefit. I will manipulate these enzymes into making new molecules to be tested for antimicrobial activity. I will focus on disrupting growth and biofilm formation in two organisms that cause infections in humans.

My findings will increase our knowledge of bacterial infections and help us find new ways to inhibit bacterial growth and/or biofilm formation.

Dr Ilaria Dorigatti

Imperial College London

Spatiotemporal dynamics of arbovirus transmission: implications for disease control and elimination

Every year, hundreds of millions of people are infected by mosquito-borne viruses, such as dengue, Chikungunya and Zika. New promising vaccines, drugs and other interventions, such as making mosquitoes resistant to infection, are in advanced development, but to make best use of these we need to improve our understanding of how these infections are transmitted. We do not yet fully understand how and why transmission varies from place to place and how it is affected by climate.

I will assess how different interventions might reduce or stop the transmission of disease. I will use mathematics and statistics to analyse data collected from case studies in Latin America to better understand how seasonal changes in climate affect transmission and the geographic spread of epidemics. I will also predict the effect of using vaccination alone and in combination with other interventions.

This research will inform policy makers on how to best use interventions to prevent disease.

Dr Vilaiwan Fernandes

University College London

Exploring glial roles in sculpting brain development

Our brains are composed of two main cell types: neurons and glia. Neurons, the electrically excitable cells that process information, have been studied intensely but glia have been thought of as support cells and are often ignored. I have recently shown that glia play essential roles in instructing brain development. Their dysfunction may therefore underlie or exacerbate many brain pathologies, underscoring the need to understand their normal roles.

We will determine how glia regulate neural development at the cellular and molecular level. Conservation of biological processes enables us to investigate this question in the fruit fly, where we can make use of modern genetic and molecular techniques to ask how signals from glia regulate neuronal production, how glia can be reprogrammed into neurons and how different types of glia differ in their functions during brain development.

Our work will improve our understanding of nervous system regeneration and neurodevelopmental disorders.

Dr Greg Findlay

University of Dundee

Functions and applications of a novel pluripotency signalling pathway

Embryonic stem cells (ESCs) are pluripotent, a property that allows them to form all cell types, tissues and organs in the adult body. ESCs hold enormous promise for cell replacement therapy and for understanding diseases. We must understand the molecular signals that instruct ESCs to remain pluripotent or to form a different cell types if we are to use them to form tissues and organs.

My laboratory has identified a new molecular signal, controlled by an enzyme called ERK5, which instructs ESCs to remain pluripotent and prevents formation of heart tissue. I will decipher the proteins and genes that ERK5 acts on to control ESC pluripotency and heart tissue formation.

My findings can be used to improve laboratory-based development of heart tissue from ESCs for cell replacement therapy and further research.

Dr Luca Fusi

King's College London

Thick filament-based mechanisms for the dynamic regulation of contraction and relaxation in the heart

During each heartbeat the myosin motors on the thick filament use ATP as a fuel to generate force by interacting with overlapping actin filaments, while during heart filling the myosin motors are switched off to inhibit ATP consumption. Dynamic regulation of the number of motors in the off or on state is essential for the graded control of strength and duration of contraction of the cardiac muscle. Defects in this dynamic regulation lead to reduced cardiac output and heart failure.

My research is focused on the regulatory systems in the thick filament that control the on/off state of the myosin motors during the heartbeat. I will use structural techniques at cellular and sub-cellular level to find out how the dynamic regulation of the myosin motors in the on or off state control the speed of contraction and relaxation in cardiac muscle.

My findings will help us understand the regulation systems that control heart muscle.

Dr Eleanor Gaunt

University of Edinburgh

The role of CpG dinucleotides in regulating virus replication kinetics

Studying the genetic code reveals patterns made by the four building blocks of our genetic make-up (adenine cytosine guanine and thymine – A, C, G and T). For example, in the human genome, G hardly ever follows C. The avoidance of CG is mimicked in the genomes of viruses that cause infections because too many CGs activate the immune response, via a protein called ZAP. There are two discrete regions in the genome of influenza A virus (IAV) that have high numbers of CG. These two regions are exclusively edited by the host cell machinery.

I will identify which proteins of an infected cell interact with these regions and characterise how ZAP affects IAV replication, by making cells that don't have ZAP and determining how viruses replicate in them. I will also characterise the differences between human and chicken ZAP to understand how IAV jumps between these hosts.

My findings will help us understand the genetic mechanisms behind influenza infections which could help develop treatments and vaccines.

Dr David Gershlick

University of Cambridge

Spatiotemporally resolved proteomics of protein trafficking pathways

Every human cell is characterised by a myriad of internal compartments. This system allows cellular components with a shared role, such as proteins, to be collected in the same place. Transport between compartments ensures the balance of cellular components. Defects in transport pathways result in protein accumulation or mislocalisation and represent a key cause of neurodegenerative disorders such as Parkinson's and Alzheimer's disease.

Recent work has revealed a way to study an under-characterised transport pathway. We can directly observe tubules budding from one intracellular compartment (the Golgi) and fusing to the target intracellular membrane. We will perform a screen using molecular technologies to characterise the cellular machinery that forms these tubules and directs them. These technologies allow components in a certain location in the cell to be labelled.

Our research will identify novel components of the cell’s transport machinery.

Dr Matthias Gruber

Cardiff University

How curiosity enhances hippocampus-dependent memory

Curiosity enhances learning, but despite the importance of curiosity in real life, we do not have a precise understanding of the mechanisms in the brain that support curiosity and curiosity-based learning.

I will use complementary neuroimaging methods to investigate which brain mechanisms support curiosity-related memory enhancements. I will focus on the brain mechanisms during the exact time periods when we are in a ‘curiosity state’: when we highly anticipate information; when we learn the actual high-curiosity information; and when our brain consolidates curiosity-related information (i.e. during rest periods while awake and during sleep).

Understanding the precise neural mechanisms underlying curiosity will help us to better spark curiosity in real life.

Dr Clare Harding

University of Glasgow

Iron in Toxoplasma gondii: sensing, acquisition and use of critical nutrient in an obligate parasite

Almost every cell needs iron to produce energy. All cells use intricate mechanisms to sense, acquire and store iron until it is needed, but pathogens face an extra hurdle as they must subvert iron from the host. I am interested in how the parasite Toxoplasma gondii senses and acquires iron from its host.

I will use genetic and biochemical techniques to study these processes to determine how the parasite responds to changes in iron concentration and investigate how this is regulated. By deleting every gene in the parasite in a pooled fashion, I will investigate how the parasite changes iron metabolism in the host and find novel parasite genes required for iron transport, storage and use.

My findings will determine how Toxoplasma uses an essential element, teaching us about parasite biology and giving us new strategies to prevent disease.

Dr Guy Harling

University College London

Using social networks to understand and intervene on HIV epidemic spread

Despite many advances, HIV remains a major problem worldwide, especially in South Africa. One reason for the ongoing epidemic is low uptake of proven interventions, such as regular HIV testing and medicines to protect at-risk people and their partners. We know that people are often more willing to change their behaviour when someone they respect suggests it. My goal is to identify who influences the behaviours of at-risk people, and how these influencers can help prevent HIV transmission.

We will follow a large group of young South Africans for three years. We will see how the important people in their lives change, and how that affects their behaviour and risk of getting HIV. We will then choose people to become peer-educators based on how influential they are. We will see if these people are better at encouraging their friends to take up interventions compared with people chosen at random.

Our findings could help prevent the transmission of HIV in at-risk groups.

Dr Caroline Hartley

University of Oxford

Understanding the relationship between apnoeas and brain function in premature infants

One in every 10 babies are born prematurely, which can have a long-term impact on brain function and cognitive ability. However, what drives these long-term effects is poorly understood. Premature infants often experience cessation of breathing, known as apnoea, which can result in decreased oxygen supply to the brain. It is unclear how this affects brain function.

I want to gain a better understanding of the mechanisms underlying the interaction between brain activity and apnoea in premature infants. I will examine whether brain activity is altered during apnoeas, and identify physiological markers that could predict apnoeas which would enable early interventions. Studying infants longitudinally, I will investigate whether frequent apnoeas alter the trajectory of brain development, and determine how this relates to cognitive ability at the age of two.

My research will enhance our understanding of apnoeas and the long-term effects of premature birth, ultimately improving outcomes for prematurely-born children.

Dr Tobias Hauser

University College London

Mapping the neurocomputational landscape of obsessive compulsive disorder

Patients with psychiatric conditions, such as obsessive compulsive disorder (OCD), are diagnosed purely based on their symptoms. However, it is likely that what we call OCD is in fact an assembly of several distinct neural illnesses. The analogy is Parkinsonism, where entirely different conditions can cause the same symptoms. Knowing the underlying causes is critical if we want to develop targeted treatments for OCD.

I will explore neural disorders that underlie OCD. I will use multimodal neuroimaging, pharmacological manipulations, computational modelling and smartphone-based big data collection in people with OCD and healthy volunteers. These techniques will allow me to determine which neural deficits can cause OCD symptomatology, whether they form distinct subgroups in OCD and whether neurotransmitter drugs have the potential to treat these subgroups.

My findings will help us go beyond symptomatic disorder classification and help us advance towards more personalised treatments for OCD.

Dr Vicky Hunt

University of Bath

The role of small RNA pathways in regulating aspects of the parasitic lifestyle and host environment by Strongyloides nematodes

Parasitic worms infect one third of the global population, causing a substantial disease burden. These worms are controlled by anthelmintic drugs but resistance is becoming increasingly widespread. Parasitic worms, like other animals, use small RNAs to regulate gene expression. I will investigate the role of small RNAs in Strongyloides worms, which infect the gut of humans and other animals. Small RNAs may regulate either the worm’s own genes or can be secreted into the host to regulate host genes.

I will use experimental and computational approaches to identify the small RNAs used by Strongyloides worms, and the worm and host genes that they regulate during an infection.

This work will elucidate the role of small RNAs in a parasite which will inform future developments of new treatment and control methods for parasitic worm infections.

Dr Armin Lak

University of Oxford

Circuit mechanisms of learning and decision making

Making decisions is part of every aspect of our lives. Research in neuroscience has identified brain regions which play fundamental roles when we make choices. However, it remains unknown how the neuronal circuits embedded in these brain regions regulate learning and decision making. Our team aims to answer this question at the level of individual neurons and their communication pathways.

We will teach mice to perform a simple decision-based task. Meanwhile, we will study the electrical activity of cells in the front part of the brain, a critical node for decision making, and dopamine-producing cells, known to be involved in learning. We will go one step further and test if we can influence learning by activating specific cellular communication pathways using novel optical methods.

This research could shed light on why and how the brain begins to dysfunction in psychiatric disorders by understanding the cellular foundation of decision making.

Dr Nicholas McGranahan

University College London

Mapping the constraints and selection pressures of lung cancer evolution

Cancers develop through an evolutionary process, whereby ‘normal’ cells accumulate genetic faults. Although some of the key genetic events leading to cancers have been identified, it is not clearly understood why certain events occur in certain tissues at certain times and not in others. Developing a deeper understanding of the processes that go awry during cancer development, coupled with a further investigation of the forces that shape a tumour’s development, including the immune system, we may be better placed to tackle cancer.

I will use data from thousands of cases of cancer to obtain a large database of how tumours from different tissues evolve over time. This database will be used to help understand how tumours change during their development, and whether we can predict the next step they are likely to take.

This work may lay the foundation for a new type of evolution-guided therapeutics.

Dr Florian Merkle

University of Cambridge

Cellular mechanisms of metabolic sensing by human hypothalamic neuron

Obesity is a major public health problem that does not have any broadly effective treatments.

I will study the cell types in the brain that regulate appetite. I have developed a method to generate large numbers of human appetite-regulating brain cells using stem cells. Like their counterparts in the brain, these cells sense and respond to metabolic signals, including nutrients and hormones such as leptin. I will explore how defects in leptin signalling might lead to obesity, how these brain cells sense metabolic signals and integrate them using specialised ‘sensory antennae’. I will also ask which combinations of anti-obesity drugs act on human appetite-regulating brain cells in culture and might therefore be effective at promoting weight loss in mice.

My studies will shed light on the cause of obesity and facilitate the development of effective anti-obesity treatments.

Dr Binyam Mogessie

University of Bristol

Actin-dependent mechanisms of chromosome segregation in mammalian eggs

Every human life starts when an egg is fertilised by a sperm. For poorly understood reasons, eggs frequently contain an incorrect number of chromosomes. This chromosomal abnormality accounts for nearly 35% of miscarriages. Chromosomal abnormality in embryos also leads to genetic disorders such as Down’s syndrome, which affects about 1 in 1,000 live births worldwide. My research is aimed at understanding which cellular processes protect eggs from having an incorrect number of chromosomes before fertilisation.

I have discovered an unexpected function of a protein called actin in preventing chromosomal abnormality in eggs and I will investigate how this protein performs this critical task.

My findings could be exploited to improve the outcomes of fertility treatments and prevent miscarriages.

Dr David Murray

University of Dundee

Structural mechanics in subcellular structure formation

Cells harbour structures that define their function. The regulation and mechanisms of the machinery that coordinate these structures are generally poorly understood, although it is known that signalling in development of cancer results in drastic changes to this area. I aim to understand the mechanics of this machinery.

I will use a reconstitution approach, building the system from minimal components through to its full complexity using protein biochemistry and membrane biophysical methods. I will explore the cellular consequences of disruptions to the coordinating machinery. The outcome of these studies will be a comprehensive model for regulation and the structural basis for coordination of subcellular structures.

An understanding of the basic mechanisms has the long-term potential for new opportunities in the treatment of cancer.

Dr Thomas Nicholls

Newcastle University

Mitochondrial DNA maintenance, propagation and disease

Human cells contain two sources of DNA: the nucleus and the mitochondrial genome (mtDNA). mtDNA is essential to life as it is required for the respiratory chain, which produces the majority of the cell's usable energy. A cell requires thousands of identical copies of mtDNA, which must be replicated, separated and distributed evenly around the cell. Defects in either mtDNA replication or distribution impair respiration, leading to human mitochondrial diseases.

I aim to understand the molecular mechanisms of the termination of mtDNA replication in human cells: how mtDNA is resolved and how this leads to efficient distribution to the mitochondrial network. I will study how and when mtDNA molecules are untangled during replication. I will also study the contribution of mtDNA segregation to mitochondrial diseases and the formation of mtDNA deletions.

These studies will link together basic mechanisms of mitochondrial genetics, bioenergetics and human disease.

Dr Mattie Pawlowic

University of Dundee

Defining oocyst wall biogenesis and function in Cryptosporidium transmission

Diarrhoeal disease is responsible for 10% of the deaths of children under five years old worldwide and Cryptosporidium is the second leading cause. There is no vaccine and the only therapy available provides no benefit to those with the highest risk of disease – young children and patients with a compromised immune system. We need a better understanding of Cryptosporidium to enable the discovery of drugs that could target the parasite.

I will use a biochemical and genetic approach to investigate transmission and identify potential therapeutic targets. Cryptosporidium are water-borne parasites that are transmitted in a hardy ‘oocyst’ shell. This shell renders them resistant to chlorination which is a common, low-cost water treatment. I have developed genetic tools that will allow us to study how Cryptosporidium builds its protective shell. By manipulating parasite genes, we can understand their role in oocyst formation and transmission.

Understanding Cryptosporidium transmission may illuminate new targets for desperately needed therapeutics.

Dr Jasper Poort

University of Cambridge

Dissecting the neural circuits for visual perceptual learning

The capacity to learn is essential for us to adapt to our environment. Visual perceptual learning (VPL) is the improved performance of a visual task after training. However, it is poorly understood whether improvements are due to changes in specialised visual brain areas or in more generalist decision-making areas, and whether improvements can transfer to tasks we have not been trained to do.

Mice quickly learn to discriminate between visual features and I will study their neural mechanisms of VPL. I will monitor and manipulate neural activity at different stages of learning to see how learning modifies responses in different visual and decision-making areas and test how these effects depend on the similarity of the visual features and task in the training context.

My research will reveal how we become experts on specific tasks, but also how learning can transfer to novel conditions.

Dr David Riglar

Imperial College London

Engineering the microbiome to expose the functional biogeography of the gut

The human gut houses a dense population of microbes that profoundly influence our health. This microbiome has been linked to susceptibility to a wide range of diseases including inflammatory bowel disease, cancer and even mental health problems. For this reason, the gut microbiome is a highly attractive target for use in the treatment and prevention of disease. There are many important details about the gut that remain poorly understood and gut bacteria are ideally situated to provide information about their surroundings.

We will use synthetic biology approaches to engineer bacteria to sense and record information about disease while traveling through the gut. Using these engineered tools, combined with advanced methods to visualise and probe bacteria inside the gut, we will investigate how the microbiome varies in its function at different locations.

Our findings could help us to develop new diagnostics and treatments for diseases that have a profound impact on global human health.

Dr Chris Schiering

Imperial College London

Dissecting the role of aryl hydrocarbon receptor in thermogenic adipose tissue

Two functionally distinct classes of adipocytes exist in both mice and humans. White adipocytes store energy while brown adipocytes burn energy to generate heat through a process termed thermogenesis. The principal function of brown adipose tissue (BAT) is to protect against hypothermia. BAT is considered an attractive therapeutic target for the treatment of obesity because of its ability to promote energy expenditure. However, there are no therapeutic agents that promote BAT activity safely. My data suggest a role for the aryl hydrocarbon receptor (AHR), a transcription factor that recognises dietary compounds, in the regulation of thermogenesis.

I will identify the cellular and molecular targets of AHR in BAT by combining conditional gene-targeting, RNA-seq and ChIP-seq approaches. I will determine whether dietary AHR ligands can enhance thermogenesis and improve metabolic disease.

My findings may facilitate the use of dietary AHR ligands for the treatment of obesity.

Dr James Sheppard

University of Oxford

STRatifying Antihypertensive Treatments In multi-morbid hypertensives for personalised management of Blood Pressure (STRATIFY-BP)

People are living for longer with more long-term physical and mental conditions which require medication. One example is people with high blood pressure who may end up taking three or four drugs to prevent stroke. As these drugs only reduce the possibility of stroke and they also have side-effects such as kidney problems, they may be doing more harm than good.

I will use information from the medical records from more than 100,000 patients to establish the link between drugs that lower blood pressure and their side-effects and develop a calculator which predicts a person’s risk of suffering harm.

This information will be used to create a support tool that can help patients and doctors make better informed decisions about starting or continuing drugs.

Dr Gülsen Sürmeli

University of Edinburgh

An investigation of distributed cortical neural circuit mechanisms for memory storage

Memories are thought to be stored as traces distributed across the brain. We do not know how these memory traces are coordinated. The entorhinal cortex receives signals from the hippocampus, which is important for initial learning, and sends outputs to diverse cortical targets that together are important for long-term memory.

I will investigate outputs from the entorhinal cortex. I will use advanced genetic and physiological methods to establish organising principles by which the entorhinal cortex coordinates neural activity within and between cortical regions. I will also use microscopic cameras to monitor cortical activity during visuospatial learning and then test the influence of projections from the entorhinal cortex.

My findings will help to identify the neural substrates for long-term memories and to explain how disparate cortical areas generate coherent cognitive states.

Dr Richard Wheeler

University of Oxford

Making it through the life cycle: motility for pathogenicity in Leishmania parasites

Leishmania parasites are single-cell microbes which cause a major human disease Leishmaniasis. In tropical environments, they are the most deadly eukaryotic microbe after Plasmodium which causes malaria. It is important for leishmania to be able to find an environment in a person's body where they thrive, or to navigate through the organs of the sandfly which transmits the disease to humans. However, we do not know precisely how and why they move, and what chemical or physical cues guide their direction.

I will discover the internal processes which control how Leishmania swim and use this to learn which signals from the cell's surroundings are important for directing them through the sandfly or finding cells to infect.

My findings will show how Leishmania movement is important for the transmission of disease.

Dr Marcus Wilson

University of Edinburgh

Mechanistic understanding of the reading and writing of DNA methylation

If DNA is the cell’s instruction manual, then methylation of this DNA creates the tabs that help to direct how the information is read and interpreted. DNA methylation is associated with compacting DNA and turning off genes, and it is faulty in many different diseases, including cancer. DNA methyl tabs are placed on DNA by molecular machines, but we do not understand how DNA methylation is deposited and maintained throughout our lifetime.

We have been limited to looking at small fragments of the bigger picture, by studying artificial snapshots of small pieces of DNA and the molecular machines involved in placing DNA methyl tabs. We will now look at more complete structures of the molecular machines that deposit DNA methylation.

By recreating the true environment where these reactions occur in the cell, we will better explain how these molecular machines work.

2017

Dr Yoshinori Aso

University of Cambridge

Bidirectional modulation of synapses and higher-order conditioning by dopamine neurons

Animals learn an association between two stimuli through their experiences. Timing is an important factor and a stimulus that animals encountered before adverse events becomes something to avoid. If animals encounter the stimulus when they have been relieved from pain, it can become attractive. Changing the strength of connection between neuronal cells is the basis of storing information in the brain. A small subset of neuronal cells that contain dopamine play a key role in such processes in all animals and their malfunction results in brain disorders such as addiction. Elucidating the mechanisms that regulate the release of dopamine and how it changes the connection between neuronal cells is an important but challenging question.

We will use fruit flies to find neuronal cells that regulate the release of dopamine and produce an anatomical database and genetic tools to manipulate them. We will prove their functions in learning and study in detail at molecular levels how dopamine modulates the connection between neuronal cells.

The new findings from this project will have broad impact on our understanding of the neuronal networks used for learning and memory-based behavioural choice.

Dr Christopher Aylett

Imperial College London

Understanding signal integration in eukaryotic cell growth

When cells decide whether or not to grow, they take into account many considerations about their environment – whether there are enough nutrients and oxygen, the outside conditions, whether the body needs to grow and if they are in the right place. Incorrect interpretations can result in tumours and allergies. We know that most of these signals activate a protein called target of rapamycin (TOR), but it is still unclear which are considered more important, or how they are combined.

This project will understand how signals are interpreted just upstream of TOR in molecular detail. We will produce the proteins responsible for carrying these signals and get them to work outside of the cell. Known incoming signals could then be applied in a controlled environment to pick apart their effects. We would also try to look at the signalling process directly using electron microscopes or light sources to visualise the molecules and understand how they work.

Our findings will improve our understanding of how the decision for a cell to grow is made and would be applicable to immunology, oncology, metabolic conditions such as diabetes, and possibly our understanding of neurology and ageing.

Dr Calum Bain

University of Edinburgh

Investigating the role of TGFβ in the functional imprinting of pulmonary macrophages in health and disease

All tissues of the body are populated with a mixture of immune cells that help protect the body from invasion by microbes. In many tissues the most abundant immune cell is the macrophage. Literally meaning ‘big eater’, macrophages capture and destroy microbial intruders, but also clear dead cells and orchestrate tissue repair after injury or infection. However, in some people the tissue repair functions of macrophages can become uncontrolled leading to excessive repair, unconstrained scar formation (fibrosis) and organ dysfunction. Idiopathic pulmonary fibrosis (IPF) is an incurable, devastating, deadly disease where progressive scarring of the lung is believed to be driven by overactive macrophages. Importantly, macrophages are very flexible cells and are easily influenced by their environment.

The aim of this study is to understand the signals that dictate macrophage behaviour in the normal lung and during successful tissue repair so that these signals can be promoted or targeted when macrophages begin to behave abnormally in disease.

Dr Thorsten Boroviak

University of Cambridge

Illuminating cell fate decisions in the implanting primate by embryo profiling and ex vivo functional analysis

Cells in the early embryo are of particular interest as they harbour the potential to form all cell types found in the adult body. Most of our knowledge about these cells is based on mouse studies. However, early development in human and non-human primates radically diverges from the rodent paradigm. Primates even form additional placental tissues upon implantation. Despite the tremendous potential for biomedical research, the underlying mechanisms remain unknown.

I propose to investigate the primate-specific aspects of early development of the embryo after implantation, building on strong collaborations with primate centres in Germany and Japan. Gene expression analysis of marmoset embryos post-implantation using the latest next-generation sequencing techniques will identify regulators of cell-fate decisions. This can only be done in a non-human primate, because human embryos at this stage cannot be used on ethical grounds. I will subsequently assemble embryo-derived cell lines into three dimensional structures, mimicking the embryo just before implantation. These synthetic embryos are a novel approach to experimentally validating the critical regulators of primate implantation in a tissue culture dish.

This model will provide unprecedented insights into human and non-human primate development with far-reaching implications for cancer and stem cell biology, placental research and treatments for implantation failure.

Dr Claire Bourke

Queen Mary University of London

The relationship between innate immune cell function and bacterial infections in severe acute malnutrition

Severe acute malnutrition (SAM) underlies one million deaths in children under five years old annually. SAM is identified by extreme weight loss, but deaths are predominantly due to infection, particularly with bacteria. The immune system is critical for controlling infections, but we know very little about how immune cells function in people who are malnourished.

I will characterise the relationship between bacterial infections and the anti-bacterial functions of two innate immune cell types – monocytes and dendritic cells (DC) – using blood samples collected from children hospitalised with SAM, and track this relationship during hospitalisation and over 48 weeks post-discharge. I will culture blood with bacterial components to determine how well monocytes and DCs bind to and become activated by bacteria, which are indicators of their capacity to control infection. I will also characterise how healthy monocytes and DC change when exposed to blood from children with SAM. I aim to determine whether monocyte and DC function are compromised when compared with adequately-nourished controls and if they are associated with death and illness due to bacterial infections; and are restored by treatment.

Understanding which defects in innate immune cell function contribute to bacterial infections in SAM could identify more effective ways of treating malnutrition.

Dr Andrew Bowman

University of Warwick

Probing the chromatin assembly pathway

Spooling of DNA around histones to form nucleosomes forms the basis of chromosome structure and is fundamental to all processes that require access to genetic material, as well as maintaining genomic integrity. Central to this process is the synthesis and delivery of histone proteins at a rate that equals DNA replication. I aim to understand the histone chaperoning pathway that has evolved to meet this need at the molecular and systems level.

I am developing and using pulse-chase approaches to define the order of binding events in the histone chaperoning pathway. I am using nuclear magnetic resonance spectroscopy to investigate the interaction between two central histone chaperoning proteins and their histone cargo.

These investigations will help delineate the multiple binding events and conformational changes that have to occur in the histone chaperoning pathway to provide mature, deposition-competent histones for DNA replication.

Dr Clare Buckley

University of Cambridge

Building and breaking epithelial integrity in the neural tube: an optogenetic approach

Most organs in the body arise from tube-like structures made from specialised polarised cells called epithelial cells. These cells have a strict apico-basal orientation; they align their apical ends along a centrally located lumen. It is thought that apico-basal polarity defects might play an early role in tissue disruption when diseases such as cancer are developing.

I will use an optogenetic approach that uses light to reversibly manipulate subcellular polarity protein location and signalling in a developing zebrafish neural tube in vivo. This will allow me to directly test how the polarity of individual cells drives the organisation of a whole organ. I will alter cell polarity and division to test how these processes are aligned during growth. I will also alter the cancer-linked PI3K signalling pathway to determine whether dysregulation of apico-basal polarity is a cause or consequence of tissue disruption.

My findings will provide information on the cellular mechanisms of disease initiation.

Dr Dhanya Cheerambathur

University of Edinburgh

Molecular mechanisms driving the formation of the neuronal microtubule cytoskeleton

Microtubule polymers are part of a vast network inside cells called the cytoskeleton. This network, although highly dynamic, can be specifically arranged to perform different cellular functions. During cell division, the cytoskeleton forms the mitotic spindle, a compact force-generating structure that separates the duplicated DNA. In contrast, during brain development the organisation is quite different, with extensive parallel structures forming inside the neurons. How the cytoskeleton can undergo such dramatic shape changes to perform specialised tasks is poorly understood. Many microtubule-associated proteins (MAPs), including stabilisers and destabilisers, operate to tune the cytoskeleton. I found that some MAPs of the mitotic spindle are also active during neurogenesis. Also, mutations in them are linked to human neurodevelopmental disorders.

I will combine genetic tools with light microscopy to understand how these proteins function and how their overall activity contributes to shaping the neuronal cytoskeleton in the model organism C. elegans and human cells.

This research will provide an insight into MAPs which could inform research into neurodevelopmental disorders.

Dr Rachel Edgar

Imperial College London

The circadian clock and viral pathogenesis

Our body clocks coordinate different biological functions over time and allow us to anticipate daily environmental changes. Sleep/wake cycles are the most obvious example of these circadian rhythms, but every cell in the body has its own molecular clock controlling a 24-hour programme of activity. In order to replicate, viruses enter host cells and commandeer their resources and then evade the immune system until they transmit to new hosts. The host environment is not constant because the body clock drives daily changes in cellular activity and the immune system. I have demonstrated that virus replication and disease severity depends on the time of day of infection.

I will investigate the host response to viruses at different times of day and during disruption to the circadian rhythm, as occurs during shift work.

This study will help us understand how our body clocks affect with infection at the molecular level. This will allow us to target our antiviral resources more effectively.

Dr Stefan Flasche

London School of Hygiene and Tropical Medicine

Using mathematical modelling to rethink global pneumococcal immunisation strategies

Despite the success of pneumococcal vaccines, two major challenges remain. First, the expansion of untargeted serotypes after vaccination, deemed serotype replacement, has mitigated the impact of vaccination which has meant that pneumococci infection remains one of the predominant causes for child death. Second, pneumococcal vaccination programmes are among the most expensive routine vaccinations, which threatens their sustainability in low income countries. Decisions on which serotypes to target using vaccination serotype replacement have been largely overlooked.

I will use global data on pneumococcal disease patterns and combine these using a model that includes dynamic replacement effects to inform design of maximal impact vaccines. Furthermore, I will estimate who infects infants with pneumococci as this information could help assessment of reduced dose vaccination schedules. I will collect data on pneumococcal transmission pathways and will extrapolate those findings to settings with different demographic and epidemiological characteristics.

My findings may result in cost savings and improved efficiency for vaccination programmes.

Dr Stephen Fleming

University College London

Improving self-awareness: manipulating the neural substrates of self-belief

As humans we often engage in self-reflection. Beliefs about our skills and abilities – our self-beliefs – may not always match reality, particularly in people with mental health disorders. For instance, someone with depression may think they won't be able to succeed in new pursuits, making them unlikely to try in the first place. Understanding how the human brain constructs these self-beliefs may lead to ways of restoring self-awareness and help treat mental health disorders.

I will conduct experiments using brain imaging technology to pinpoint the characteristics and location of neural activity which creates self-beliefs in the human brain. I will give people tasks to distinguish different influences on self-belief and collect data over the web to test large numbers of people and ask how these components are linked to mental health. Using this knowledge I will devise ways of changing self-beliefs, for instance by changing brain activity in real time.

The ultimate goal of my research is to understand the machinery supporting self-beliefs, allowing us to intervene in cases in which these mechanisms are broken. 

Dr Fabian Grabenhorst

University of Cambridge

Neurophysiology of nutrient rewards in monkeys and humans

How do we decide what to eat? Why do we like some foods more than others – and sometimes consume too much of them? Every day, we make plans to pursue and consume our favourite foods. Specific nutrients, such as fats and sugars, are particularly effective rewards that provide us with necessary calories but also contribute to obesity.

We will investigate the brain mechanisms of sophisticated eating behaviours typical of primates that are directed toward specific nutrients. We will study information processing in individual neurons as monkeys form decisions and consumption plans for prospective nutrient rewards and learn nutrient values from social partners and model partners’ choices. In closely related neuroimaging experiments, we will study brain activity in humans with the same foods and behaviours, to advance the detailed single-cell findings to brain networks, individual differences and real-life eating preferences. We will combine the data to build biologically realistic computer simulations of brain systems to explain food intake in terms of neural information processing.

To our knowledge, this is the only translational neurophysiology project worldwide focusing on primates’ food intake mechanisms. Understanding these mechanisms is not only a fundamental biological question but also has implications for understanding overeating and obesity.

Dr Gibran Hemani

University of Bristol

The causal map of the human phenome

The human phenome – the collection of all possible human characteristics – is vast and includes measures from the molecular level to whole-body physiology. These characteristics vary dramatically between tissues, time points and people. It could be that this variation is driving disease.

I will use genetic data from millions of people to construct an atlas describing the causal relationships that link every available molecular measure to every available disease phenotype. This will span billions of relationships.

A model like this can be used to understand what happens if we upset the system. I will use the model to infer the past and future trajectories of human evolution and predict the safety and effectiveness of new drugs.

Dr Catarina Henriques

University of Sheffield

Determining the mechanisms regulating immune-directed clearance of senescent cells to promote healthy ageing

As we age, we develop chronic diseases that diminish our quality of life. The number of people over the age of 65 is set to double over the next 50 years and we urgently need to develop effective therapies to improve health and prevent chronic illness in older people. A major medical problem associated with ageing is that the different tissues in our bodies become damaged over time. A major reason for this is the accumulation of old or senescent cells. It is likely that, as we age, our immune system becomes defective in its ability to clear senescent cells from tissues and if we could understand this process, we might be able to put it right.

My work will determine which immune cells are responsible for clearing senescent cells and whether they are impaired by ageing. Importantly, I will determine the reasons behind this and devise a strategy to promote the clearance of senescent cells in aged, damaged tissues.

The ultimate aim of my work is to discover new ways to stimulate our natural immune system to clear senescent cells, promoting healthy long life.

Dr Seamus Holden

University of Newcastle

Super-resolving the physical mechanisms of bacterial cell division

Antibiotic-resistant bacteria are a major challenge to our society, threatening to return us to the pre-antibiotic era where even a minor scratch could kill if it became infected. We need to better understand bacteria at a fundamental level to identify genuinely new strategies for antibiotic development. Bacterial cell division is an utterly essential process and an excellent target for new antibiotics. Bacteria divide against high internal pressure, which is like trying to cut an inflated balloon in two without bursting it. For decades, this process has been mysterious, because cell division occurs on the nanoscale, invisible to a conventional microscope.

I will use super-resolution microscopy to discover the basic principles of how bacteria divide. This is a recently developed technique that can observe single protein molecules in living cells at a resolution of tens of nanometres. I will reveal the organisation and motion of individual cell division proteins in live bacteria. This will show how the cell division proteins work together as a single nanoscale machine to cut the bacterial cell wall in two.

My findings will help in the development of new antibiotics that target cell division.

Dr Laurence Hunt

University of Oxford

Neural circuitry and neurochemistry of decision making

We often attempt to manipulate brain chemistry in order to treat psychiatric symptoms, but we don't yet understand how to link chemical changes to changes in motivation and decision making. My research aims to understand the relationship between our brain chemistry and our decision making behaviour.

I will collect brain imaging data for humans performing simple tasks involving decision making. I will collaborate with other researchers who record cellular data in animals performing similar tasks. I will study the effects of psychiatric drugs on relevant brain activity and relate the complementary information derived from human and animal studies. This will provide some of the missing links between molecular and behavioural explanations of drug interventions in health and disease.

This study is important for understanding how the brain makes decisions, and its findings may contribute to the development of new treatments for mental health conditions.

Dr Michael Imbeault

University of Cambridge

KRAB-ZFPs and the establishment of lineage- and species-specific gene regulatory networks

KRAB-ZFPs are a family of proteins so numerous that it was unreasonable to study them on a large scale until recently. Through indirect studies of a common cofactor, they were known for their role in ensuring that invaders of viral origin residing in our genome remain dormant. My post-doctoral work showed where each human KRAB-ZFP binds in the genome although the biological role of most of them remains nebulous. We found significant evidence indicating that that they could influence regulation of cellular genes at a distance.

We will investigate this hypothesis and determine if they can help explain many of the differences that exist between species (for example, mouse and human). We also want to improve our understanding of how they can generate these differences by comparing how the same sequences evolved in many related species. We will pay special attention to variability between people, using new genome sequencing data.

Dr Luke Jostins-Dean

University of Oxford

Combining genetics and high-resolution cell phenotyping to map pathways underlying inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disorder of the digestive system which affects 1 in 250 Europeans. It is likely that it is caused by a combination of environmental exposure and genetic susceptibility. We have discovered hundreds of genetic variants that increase the risk of having IBD, but we know little about how these variants actually change the immune system.

We will develop computational techniques and generate new data to identify immune cells where IBD genes are active, and work with immunologists to determine how to measure these cells' function. We will collect and isolate these cells from patients with IBD and healthy controls and measure how risk variants affect IBD genes and cell function. We will test whether these cells predict disease prognosis, and work with clinicians to plan new studies to determine whether monitoring or drugging these cells could help treat patients.

Our findings could help develop new ways to treat people with IBD.

Dr Adil Khan

King's College London

Circuit mechanisms of cognitive control

Animals must be flexible so they can survive as this allows them to react differently to the same stimuli depending on the context. For example, the smell of smoke will probably elicit very different behavioural responses if you are in your house or you are at a barbecue. However, the way the brain selects different actions in response to the same stimulus remains a mystery.

I will investigate the neural mechanisms of such behavioural flexibility. Mice are capable of performing highly flexible behaviours and they are ideal for this study because powerful techniques exist for measuring and manipulating the activity of neurons in the mouse brain. In this project I will study flexible behaviour in which mice are trained to change their responses to the same stimulus every few minutes. The mice will be placed in a virtual reality environment and I will study their brains during this flexible behaviour. I will study the prefrontal cortex, which has a crucial role in generating flexible behaviour and I will test if the prefrontal cortex acts as a switchboard, routing information to different brain regions at different times, depending on the current context.

This study will shed light on the circuit mechanisms of cognitive control in the prefrontal cortex.

Dr Golnar Kolahgar

University of Cambridge

Revealing how cells read the environment to regulate adult gut renewal

The gut is composed of thousands of specialised cells allowing it to fulfil complex roles underpinning the health of the organism. While digesting food and fighting off pathogens, the gut must also maintain itself by replacing cells after they pass their ‘expiry date’. This relies on stem cells that divide to maintain the necessary number and type of cells. Our goal is to understand how the stem cells know how fast they are required to proliferate. This is important, because degenerative diseases or cancer can form when the information that instructs stem cells is not conveyed properly.

We will focus on discovering molecules that instruct cells to multiply in the gut and on understanding how gut distortion influences decisions about cell proliferation. We work with the intestine of the fruit fly Drosophila due to the ease with which it can be genetically manipulated and imaged using microscopy, its rapid life cycle and its cost-effectiveness.

As Drosophila shares 70% of its DNA with human disease genes, our research may contribute to the design of new therapies against a range of intestinal diseases.

Dr Julija Krupic

University of Cambridge

Space distortions: towards a general framework of the hippocampal cognitive map

The hippocampal formation is crucial for episodic memories and represents the internal GPS system of the brain. Although the basic spatial properties of neurons in the hippocampus and its major hub, the medial entorhinal cortex (mEC), are well characterised, questions remain about where and how spatial representations are constructed and what their functional roles are in navigation. The major theoretical models assume that hippocampal spatial representations are generated by mEC cells. Our previous findings called into question these assumptions and suggested a greater role for hippocampal spatial cells in shaping neural activity in the mEC.

I propose to manipulate neural activity at the single-cell level in a defined set of hippocampal cells projecting to the same mEC target cell and study how new representations emerge and how they are reflected in an animal’s behaviour.
The mEC is one of the first areas affected during Alzheimer’s disease and understanding the functional role the mEC plays in navigation would be an important breakthrough in the much-needed early diagnosis of the disease.

Dr Adam Kucharski

London School of Hygiene and Tropical Medicine

Immunity dynamics and epidemiology of cross-reactive pathogens

Infections such as dengue fever, Zika and influenza generate a substantial public heath burden. It is therefore crucial to understand the biological mechanisms driving infection and immunity in individuals, and how these shape population-level epidemic dynamics. However, people can experience multiple infections over the course of their lifetime, which makes it challenging to analyse immune responses and the implications for future outbreaks.

This project aims to address this knowledge gap using a combination of new mathematical methods and field studies. I will examine the human immune response to dengue, Zika and influenza viruses. I plan to untangle the different factors that influence observed patterns of immunity using new mathematical and statistical methods. As well as improving our knowledge of people’s life history of infection and immunity, the work will also guide the design of future field studies, enabling researchers to address a wider range of hypotheses about viruses such as influenza and dengue. In particular, I will investigate how immunity shapes influenza evolution, and the emergence (and re-emergence) of new infections in different areas.

With a better understanding of individual-level immune responses, it will also be possible to investigate the impact of immunity at the population level.

Dr Delphine Larrieu

University of Cambridge

Regulation of nuclear envelope function and links with disease

Human cells are highly organised and regulated, which is essential for the healthy function of tissues and organs. Recently, it has become evident that one crucial part of the cell is a structure called the nuclear envelope (NE), surrounding the cell nucleus – home to our DNA. The NE is crucial for maintaining nuclear architecture and cell function. Dysfunction of the NE leads to various human diseases, including cancer, muscular diseases, neurodegenerative syndromes and premature ageing syndromes called progeria. The fact that NE defects are associated with various human diseases and with normal ageing has triggered a strong interest in trying to correct the abnormal nuclei and associated defects in NE-associated syndromes as this will improve cell fitness and patient survival. Unfortunately, there is no effective treatment for these diseases, and the available therapies mainly act by improving the symptoms of these patients.

I plan to characterise new mechanisms that regulate NE function. This work will improve our fundamental knowledge of NE function and will suggest new ways of treating these diseases. Moreover, this work could also open up new perspectives into improving normal age-related pathologies, which would have a great impact on public health.

Dr Rebecca Lawson

University of Cambridge

Contextual determinants of surprise in health, development and disorder

A new hypothesis suggests that people with autism might struggle to make sense of the world because their brains do not form the correct expectation for a given situation, resulting in constant mild surprise. Imagine, for example, how surprising the first taste of a lemon might be if you expected it to taste sweet like other fruits. New evidence suggests this might be explained by mathematical models that describe how surprises are computed and the action of brain chemicals, called neuromodulators, which signal when something unexpected has happened. However, more work is needed to understand the brain processes that underpin surprise, how these brain differences develop and also how they differ across disorders.

We will use brain imaging to better understand how neuromodulators signal surprise in healthy volunteers. We will also measure the surprise response in the brains of babies to see if this can predict emergence of autism symptoms. We will also examine whether measuring surprise responses enables autism to be distinguished from related neuropsychiatric conditions.

Dr Tony Ly

University of Edinburgh

Understanding the proliferation-quiescence switch using quantitative cellular biochemistry

Cells grow and divide to produce new cells in a regulated process known as the cell cycle. Most cells in adults are non-dividing or quiescent. The ability to switch reversibly from a quiescent state to a dividing state is essential for renewing and repairing old or damaged tissues. The cell cycle has four phases: gap 1 (G1), synthesis (where new DNA is made), gap 2 (G2) and mitosis or cell division. Cells can enter or exit the cycle during the gap phases. However, what happens in these phases is poorly understood, largely because we lack ways of defining progress through these phases. Progress through the cell cycle is dependent on the amount of specific proteins at different times.

I aim to understand what happens to all of the different proteins in the cell when they enter and progress through G1. I have developed a sensitive way of separating cells into different cell cycle stages and by measuring how much of each regulatory protein is present. I can test whether our current ideas of how the process is controlled are correct or if we are missing important pieces of the puzzle.

Dr Elizabeth Mann

University of Manchester

The role of the gut microbiota in regulating mucosal macrophage homeostasis and inflammation

Our immune system must fight harmful pathogens, but remain silent against harmless substances such as the trillions of bacteria found in the gut that are beneficial for health. If our immune system attacks these microbiota, inflammatory bowel diseases (IBD), such as Crohn’s disease, can occur. These are painful, debilitating conditions that affect millions of people worldwide, and although the causes are poorly understood, there is mounting evidence that previous antibiotic use may be important, especially if used in early life. However, it is unknown why use of antibiotics increases IBD risk. My preliminary results indicate that antibiotic use causes immune cells called macrophages to become overactive in the gut, resulting in long-lived inflammation.

I will examine how antibiotics cause changes in gut macrophages that may lead to IBD. As it is now known that antibiotic use in childhood also predisposes to asthma, I will explore if antibiotics also make lung macrophages more active and if this contributes to inflammatory disease in the lung.

This study will determine how gut and lung macrophages control the immune system in health and how antibiotic use might disrupt this process, allowing inflammation to develop, with the potential for identifying new drug targets.

Dr William McEwan

University of Cambridge

Self-propagating protein conformations as targets of intracellular immunity

The immune system is tasked with the detection and destruction of pathogens. Prion-like proteins, whose replication is thought to underlie neurodegenerative diseases, are the simplest type of pathogen but the hardest to protect against. This is because they are formed from self-derived material, which makes them difficult to detect, and they are highly compact structures, making them difficult to destroy. There is accordingly little understanding of how the immune system can effectively limit the spread of prion-like proteins.

I have co-discovered a novel antibody receptor, TRIM21, which can detect antibody-coated viruses inside the cell and strip them apart, preventing them from replicating. I will investigate how this mechanism could be redirected to target prion-like proteins using therapeutic antibodies. I have established experimental systems to allow the replication of tau, a prion-like protein seen in Alzheimer’s disease, to be studied in detail. These assays will be used to determine the molecular mechanisms by which protein pathogens are neutralised. In parallel, I will use mouse and stem cell-derived models of tau pathology to test whether this TRIM21-dependent mechanism can provide protection in a physiological setting.

These results could provide a mechanism-based strategy for antibody-based therapies for neurodegeneration.

Dr Charlotte Odendall

King's College London

Type III interferons in immunity against bacteria

Cells of the immune system secrete proteins called interferons (IFNs) when they communicate. I study IFNs of the type III family (IFNλs) that are important regulators of intestinal immunity. I have found that IFNλs are produced in response to infection with intestinal bacteria such as Salmonella, Shigella and E. coli. I also found that mice that do not have an IFNλ system are unable to fight Salmonella infection as efficiently, and that IFNλs protect the intestinal barrier from damage inflicted by bacteria. Pathogenic bacteria have also devised virulence mechanisms to block IFNλ production. My findings suggest that type III IFNs are indeed important for our immune system to fight bacterial infections.

I will study this in greater detail by examining how IFNλs block bacterial growth in infected animals and infected cells. I will also identify how host cells produce IFNλs in response to bacterial components. I aim to identify the bacterial factors that pathogenic bacteria use to block IFNλ expression and signalling.

This project will advance our understanding of intestinal immunity and how some bacterial pathogens cause disease by interfering with this aspect of the immune system.

Dr Jonathan O'Muircheartaigh

King's College London

Imaging focal epilepsy in children: a developmental perspective

Epilepsy is the most common neurological disorder in children. About 30% of children with epilepsy do not respond to medical treatment and for these patients surgical removal of the brain tissue that generates seizures may be an effective treatment. Identifying regions in the brain that cause seizures using magnetic resonance imaging (MRI) can be a predictor of good outcome after surgery. Identifying these using MRI for children and infants is complicated by the extensive changes occurring during normal brain development, as well as the variability in how brain images are collected between hospitals.

I plan to investigate how the brain develops in a group of children who do not have epilepsy and will try to predict where there is a brain abnormality in children with epilepsy. I have drawn together an international consortium of collaborators with widespread expertise and a critical mass of data. I will address these questions by creating models of early brain development in both health and disease.

At the end of this study I plan to develop and release analytical tools that will help inform future clinical decision-making for epilepsy and related neurological and neurodevelopmental disorders. 

Dr Virginia Pedicord

University of Cambridge

Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity

Intestinal infections affect billions of people worldwide and result in nearly 1.4 million deaths each year. Normal intestinal bacteria, known as the microbiota, can prevent pathogenic infections as demonstrated by increased susceptibility to infection when using antibiotics. However, the mechanisms of microbiota-mediated protection are not well characterised and therefore cannot be used to engineer effective therapies. I have recently shown that Enterococcus faecium, normally found at low abundance in the human gut, is able to reduce disease caused by the pathogens Salmonella and Clostridium difficile when administered as a probiotic. I found this out from cues from E. faecium that are able to activate the intestinal epithelium.

My research will use advanced approaches to dissect the mechanisms by which normal intestinal bacteria activate and prepare the intestinal epithelium and the vast network of underlying immune cells to fight infections.

Revealing the defense mechanisms triggered in the intestinal epithelium by the microbiota will enable better strategies to prevent and treat intestinal infections and inflammation.

Dr Mahima Swamy

University of Dundee

Molecular determinants of intraepithelial lymphocyte function in intestinal infection

Our bodies are home to trillions of bacteria and most of them reside in our guts. Recent research has suggested a strong link between intestinal bacteria and inflammatory diseases including cardiovascular complaints, obesity, and inflammatory bowel diseases.

A single layer of epithelial cells forms the first line of defence in the gut and is the largest interface between microbes and our bodies. This layer of cells is interspersed with specialised immune cells that help to protect it. I will explore the function of these special cells, named intraepithelial lymphocytes (IEL), and investigate how they identify an epithelial cell that has been infected with a disease-causing microbe. I will explore the nature of the IEL response and how IEL kill infected cells. A clearer understanding of the early immune reaction that result from such pathogenic infections and the mechanisms used will help us understand how the immune system mounts an appropriate response to clear the disease.

This work will identify key factors that must be induced for efficient vaccine design against gut pathogens which could help us fight infectious diarrhoea, one of the leading causes of global morbidity.

Dr Felipe Karam Teixeira

University of Cambridge

Molecular mechanisms controlling germline stem cell biology

Maintenance of stem cell populations, as well as the control of self-renewal and differentiation is essential for proper development and tissue homeostasis in animals. Indeed, ablation of the stem cell population can lead to organ malformation and tissue replacement defects, affecting longevity or fertility. The same is true for unbalanced shifts between stem cell self-renewal and differentiation, which can directly affect tissue architecture and regeneration capacity, as well as leading to tumours. Even though the commitment to differentiate must be very well controlled, our understanding of these processes remains limited.

I will investigate the mechanisms that regulate stem cell biology in vivo by using the germline as a model system and employing a variety of genetic, molecular and developmental analyses. In particular, I am interest in understanding how changes in gene expression control the balance between stem cell self-renewal and differentiation.

Given the importance of stem cells for development and survival, this research is not only of broad interest to biologists and stem cell researchers, but has direct implications on regenerative medicine, ageing, and cancer.

Dr Aartjan Te Velthuis

University of Cambridge

Understanding the role of the viral polymerase in influenza virus virulence

‘A’ strain viruses cause annual epidemics that lead to about half a million deaths each year. Occasionally, highly pathogenic influenza A viruses, such as the Spanish Flu of 1918, emerge causing pandemics with an even higher death count. The reason for their pathogenicity is a dysregulated immune response, but the molecular mechanism that triggers this is not fully understood. Recent data show that the enzyme that copies the influenza virus genome, the RNA polymerase, may contribute to the induction of this strong immune response by creating large amounts of aberrant copies of the viral genome that can readily trigger an immune response. Interestingly, the RNA polymerases of highly pathogenic influenza A viruses produce vastly more of these aberrant products than the RNA polymerases of seasonal influenza viruses and a much stronger immune response as a result. This suggests a direct link between the activity of the RNA polymerase and the strength of the immune response.

This project aims to deliver a significant advance in our general understanding of influenza replication and why ostensibly simple differences between pathogenic and seasonal influenza A viruses lead to such dramatically different outcomes. 

Dr Calvin Tiengwe

Imperial College London

Unravelling novel molecular mechanisms of iron-sensing in African trypanosomes

Every organism requires iron as an essential nutrient for survival. In mammals, iron is sequestered by a protein called transferrin and imported into the cell by the transferrin receptor. When iron levels are low, iron-sensing RNA-binding proteins bind iron-regulatory RNA elements to increase transferrin receptor expression. Intracellular iron-regulatory processes have been studied in many organisms, but not extensively in parasitic trypanosomes that infect humans and animals.

Using global comparative RNA-sequencing data under iron-starved and iron-sufficient conditions, I have identified novel parasite-specific genes acting in this pathway. I aim to study the function of these genes using targeted deletions and/or overexpression. I will use proteomic approaches to systematically map the network of proteins and the pathway(s) that sense and respond to iron starvation in trypanosomes.

Identification of differences in iron-stress response pathways between mammalian host and trypanosome parasites can direct future drug design and improve treatments.

Dr Claire Turner

University of Sheffield

Characterisation of the factors that underpin the success of emergent group A Streptococcus variants using novel human tonsil infection models

The bacterium group A streptococcus (GAS) causes tonsillitis and skin conditions, as well as severe infections such as ‘flesh-eating’ disease. Sudden local and national increases in GAS disease are frequent, but the mechanisms behind these increases are unclear. Whole genome sequencing of strains responsible for upsurges in disease has revealed that major genetic changes can occur that result in an increased production of GAS toxins. A rise in toxin production may allow GAS to better initiate and maintain infections.

I will develop new laboratory-based models of human tonsil infection using human tonsil tissue obtained from routine tonsillectomies. I will use various culture techniques, including 3D tissue-engineering. These models will be used to study the critical interactions that allow GAS to cause infection, including the role of GAS toxins.

My findings will result in better understanding of what allows new strains of GAS to succeed in the human population and potential points that could be targeted for intervention.

Dr Stephan Uphoff

University of Oxford

Stochastic variation and regulation of bacterial DNA repair and mutagenesis

The rapid evolution and spread of antibiotic resistance is a major threat to global health. It is rooted in the plasticity of bacterial genomes. There is growing evidence that the overuse of antibiotics not only promotes the spread of existing resistant genes, but also accelerates evolution of novel resistance mechanisms. Cellular stress and DNA damage responses appear to increase mutation rates during antibiotic treatment, but the molecular mechanisms remain unclear.

My research shows that mutation rates can vary between cells in a population, which may help a small fraction of cells to survive drug treatment and acquire genetic resistance. Conventional experiments on large cell populations cannot show the specific intracellular conditions that lead to a mutation in an individual cell. I will measure the movement of single proteins that repair DNA sequence errors inside living cells so I can identify mutation events under the microscope and map them to the genome sequence to identify the molecular processes that cause mutations.

These novel tools will show how antibiotic treatment speeds up the evolution of resistance. My research into the fundamental mechanisms of mutagenesis will also inform on equivalent processes in humans, where the accumulation of mutation leads to cancer.

Dr Edward Wallace

University of Edinburgh

Dynamic regulation of mRNA processing in adapting fungi

How do fungi survive in a changing environment when they cannot move away from danger or towards food? And how do infectious fungi begin to grow in a human body? Fungi have a toolbox of RNA and protein and when they are under stress they get out some tools and put others away. For example, when fungi are hot, they shut down heat-sensitive processes and concentrate on making proteins that protect them against heat. 

I will explore how cells move RNAs when they are dangerously hot, by measuring movement of a large collection of synthetic RNAs. I will also investigate the function of the Ssd1 protein that is essential for fungi to survive stress. I will measure the exact locations on RNAs that contact Ssd1, and how that affects cell survival. I will also find out what the first changes to RNA and protein are as Cryptococcus neoformans infection begins in a lung.     

My findings will improve our understanding of how fungal infections develop.

Dr Helen Weavers

University of Bristol

Cytoprotective defence mechanisms during tissue maintenance and repair

Our skin is a physical barrier against the environment and it quickly repairs after it is damaged. Inflammatory cells fight off wound infection using toxic chemicals called reactive oxygen species (ROS). Although this bactericidal response is beneficial, high ROS levels are dangerous as they can damage the body’s own cells (including DNA) in a process called oxidative stress. Oxidative stress is linked to diseases, ageing, infertility and cancer. ROS are by-products of normal cellular metabolism and many other body tissues are susceptible to oxidative damage. Our bodies have therefore evolved complex cytoprotective defence strategies that minimise this collateral damage.

I will use a multidisciplinary approach, combining live imaging in a genetically tractable Drosophila model with analysis of human disease datasets to explore how vulnerable metabolically active tissues, including kidneys and reproductive organs and damaged tissue that is undergoing repair, detoxify ROS and repair damage to DNA.

This work could have important clinical therapeutic applications relating to ageing, infertility and cancer.

2016

Dr Tanmay Bharat

University of Oxford

Structural cell biology of bacterial biofilm formation

Bacterial cells can attach to surfaces and form large communities known as biofilms. Cells in a biofilm community are tolerant to a wide variety of environmental stresses. Most notably they can become tolerant to antibiotics. Two such bacteria are Escherichia coli and Pseudomonas aeruginosa. Both of these bacteria can enter the human body, form a biofilm in the infected tissue and lead to disease. Understanding how bacterial biofilms are built is therefore important to understand the infection process of these pathogenic bacteria. 

Recent developments in microscopic imaging methods, that use electrons rather than light, have provided an important alternative method for researchers to investigate biological material. It is Tanmay’s goal to apply the latest electron microscopy imaging technology to study bacterial biofilms. 

I will use electron microscopy imaging to produce high-resolution pictures of bacterial biofilms in 3D. I will use these pictures to work out where key molecules that mediate biofilm formation are located. I will use electron microscopy methods to solve the atomic structures of these key molecules in order to understand how they influence biofilm formation. Together, these experiments may lead to ideas on how to disrupt bacterial biofilms and help infected individuals.

Dr Stephen Burgess

University of Cambridge

Genetics and causality: towards more accessible and more reliable Mendelian randomisation investigations

An observational correlation between a suspected risk factor and a disease outcome does not imply that changes in the risk factor will necessarily have a causal impact on disease risk. This is often discussed as ‘correlation is not causation’. One way to assess whether a relationship is causal is to look at genetics, as genetic variants do not tend to be associated with differences in socio-economic or environmental factors that make observations of causality unreliable. If genetic predictors of the risk factor are also associated with the outcome, this increases the plausibility that the risk factor is a causal determinant of disease risk. However, if the genetic variants in the analysis do not have a specific biological link to the risk factor, then the same problems in inferring a causal relationship remain.

My research aims to develop methods using genetic variants for making causal inferences that are more accessible and reliable. I will work with clinicians and epidemiologists to apply these methods to assess the causal effects of a range of risk factors on disease outcomes and to discover risk factors that may be good targets for drug development.

Dr Kyra Campbell

University of Sheffield

The molecular mechanisms underlying epithelial cell plasticity

In many cancers, cells acquire abnormal motile behaviours leading to metastasis, the main cause of cancer-related deaths. It is now clear that processes normally driving the tightly-controlled movement of cells during development, are reactivated in metastatic cancers in a dysregulated manner. These processes are called the epithelial-to-mesenchymal transition (EMT) and the reverse process is mesenchymal-epithelial-transition (MET). They enable cells to reversibly switch between stationary and migratory cell states. The molecular mechanisms orchestrating both processes remain poorly understood.

I will use a model organism, the fruit fly drosophila melanogaster, to study the basic biology of these processes during normal development. Long recognised as a valuable model for basic research, the fruit fly is now emerging as a powerful tool to investigate malignancy and identify possible new therapies. I will use genetic tools and systems biology approaches to identify the molecular mechanisms underlying EMT and MET and microscopy to follow the behaviour of cells undergoing these processes in real time.

My goal is to determine the molecular machinery driving the processes of EMT and MET and consequently identify novel targets that will aid the diagnosis, prognosis and treatment of metastatic cancer.

Dr Nick Casewell

Liverpool School of Tropical Medicine

Developing a universal antivenom to treat snake venom-induced consumption coagulopathy

Snakebite is a neglected tropical disease that kills around 100,000 people each year. Different snakes have different venoms, and for this reason antivenom therapies are limited to treating patients bitten by certain snakes. One of the most common pathologies caused by snakebite is incoagulable blood. 

I will aim to develop a single antivenom that can be used anywhere in the world to treat snakebite patients suffering with incoagulable blood. This new antivenom will be the first of its kind – a purposely designed ‘pathology-specific’ antivenom that will only require low doses and be much safer than existing antivenoms. I will use modern technologies for its development, first using ‘proteomics’ to determine which venom toxins in different snakes cause incoagulable blood and then targeting these components by making monoclonal antibodies that neutralise them.

Dr Jenna Cash

University of Edinburgh

Understanding macrophage phenotypes in normal and pathological healing: harnessing pro-resolving pathways to drive repair

When skin is injured, a repair response commences that involves an inflammatory phase in which white blood cells, including macrophages, are recruited to the wound site to support the repair process. Wounds typically heal within days or weeks, but a growing number are failing to heal. This inflicts debilitating personal costs on patients and a burden on healthcare systems. These wounds are chronically inflamed, with their macrophages often described as dysfunctional. Pathways which regulate the balance between acute wound inflammation resolution versus chronic wound inflammation persistence represent potential therapeutic targets to alleviate aberrant healing.

I am interested in studying normal and pathological healing to ascertain what kinds of macrophages are present throughout the diverse phases of normal repair. I will study how they behave, how they change in wounds that fail to heal and how this impacts the repair outcome. I will also study pathways that help terminate the inflammatory response to determine whether we can harness them to accelerate wound repair or rescue chronic wounds that have become ‘stuck’ in the inflammatory phase.

The overall goal of my research is to achieve an improved understanding of the events that determine whether a skin wound heals acutely or develops into a chronic wound.

Dr Leifu Chang

University of Leeds

Structure and molecular mechanism of the Augmin complex in mitotic spindle assembly

Accurate separation of genetic material into two daughter cells is a main objective of cell division. Failure in this process results in genome instability and cancer. The mitotic spindle is the apparatus in the cell that fulfils this task. The spindle has two poles to define the positions of two daughter cells. Filament-like structures called microtubules emanate from the poles, search and capture chromosomes and align them in the centre into a ready-to-separate state. The spindle then provides force to pull apart sister chromatids towards two opposite poles. Spindle assembly involves hundreds of proteins. The augmin complex, composed of eight distinct proteins, plays a critical role in spindle assembly and its depletion causes decreased microtubule density in the spindle and defects such as formation of multipolar spindles.

I propose to determine the atomic structure of human augmin complex and augmin-microtubule complex by cryo-electron microscopy, which will provide important insights into how this complex works. I will also explore how the augmin complex is regulated by mitotic phosphorylation.

Since the augmin complex is essential for proper formation of the spindle for cell division, it could be a new target to develop small-molecule-inhibitor drugs to treat cancer.

Dr Matthew Child

Imperial College London

A chemical biology investigation of hydrogen peroxide signalling in Toxoplasma

When viruses infect a cell they often display structures that are sensed as foreign. After detection, signalling pathways result in the production of proteins called interferons. These proteins induce the production of hundreds of other proteins called interferon-stimulated genes in the infected and neighbouring cells to fend off the viral infection.

I have shown that the interferon-induced protein with tetratricopeptide repeats-1 (IFIT1) preferentially binds RNA with improperly processed ends and blocks the production of protein from this RNA. However, the role of IFIT1 in the antiviral response is still not clear since the only viruses affected by this RNA binding activity are those genetically engineered to be susceptible. There is also evidence to suggest that IFIT1 can bind fully processed RNAs. My hypothesis is that IFIT1 can interact with cellular RNA and that this interaction is important for the antiviral response. I will use multiple cutting-edge RNA/protein analysis approaches to determine what RNAs IFIT1 binds and their fate, how RNA binding regulates IFIT1 protein-protein interactions and what affect IFIT1 has on translation in the whole cell.

By understanding the impact of IFIT1 on the cell we will gain an insight into its role in the host antiviral response.

Dr Edward Chouchani

University of Cambridge

Defining mechanisms of mitochondrial redox control over adipose function for treatment of metabolic disorders

Obesity is a global epidemic fuelled by ageing populations and poor dietary habits. The health consequences of obesity are widespread and escalating as it’s a major risk factor for leading causes of death including diabetes, cardiovascular disease and cancer. The results are ever-expanding numbers of chronically ill individuals, unsustainable healthcare expenses, and the prediction that the current generation will have a shorter lifespan than those previous.

Accumulation of white fat drives obesity. We now know that a second type of healthy ‘brown’ fat can counteract obesity and diabetes. Recently, I showed that the anti-obesity effects of this healthy brown fat can be stimulated by metabolic signals called mitochondrial reactive oxygen species (mtROS). Different mtROS signals are also thought to be important for the deadly consequences of unhealthy white fat. If we understand how these critical signals act differently in healthy versus unhealthy adipose, we can manipulate them as a new way of treating metabolic disease.

My research focus is to understand how mtROS signals in fat can be manipulated. This will provide new strategies for treating obesity and related metabolic disorders.

Dr Calliope Dendrou

University of Oxford

Investigating the functional basis of shared genetic aetiology across autoimmune diseases

Autoimmune diseases are thought to arise when cells of the immune system, which normally fight off infections, become inappropriately activated and instead mount a response against the body leading to pervasive tissue damage. These diseases, which include conditions such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and inflammatory bowel disease, are estimated to afflict about 10% of the population worldwide. They pose a substantial personal and socioeconomic burden and they have no cure. There is a fundamental need to develop improved therapeutic strategies to treat these diseases through an optimal modulation of the immune system that allows substantial symptom alleviation but without leading to the severe or even fatal side-effects that can occur with currently available treatments.

Interrogating the biological consequences of genetic factors that contribute to the development of multiple autoimmune conditions provides an approach that can uncover the key mechanisms that underpin these diseases. I will investigate the basis of shared genetic risk across different autoimmune conditions at the molecular level and determine the downstream cellular changes arising due to the genetically determined molecular differences and help define key disease pathways. I will also investigate the best way to regulate key disease pathways.

Dr Elena Dreosti

University College London

The neural circuits of social preference

Humans are fundamentally social beings. Our ability to consider the thoughts of others and communicate with them is unparalleled. However, even the most complex social skill requires a basic drive to approach other members of our species. This essential social preference is hard-wired into our brain. For example, newborns immediately prefer to look at faces. If this preference is somehow lost, then our entire social development will be affected.

I want to know how this basic social drive is built into the brain so that we can understand how it might be impaired. This is difficult to study in humans because the brain circuits involved are established before we are born. Brains that develop ex utero can be studied in much more detail.

One such brain is that of the zebrafish. These small fish are transparent when young and develop from a single cell into a social organism in just a few weeks. They provide a unique opportunity to watch the circuitry that creates social preference form, and to see what goes wrong in developmental diseases like autism.

Dr Nuno Faria

University of Oxford

Real-time genetic cartography of viral epidemics

The ignition and rapid spread of viral pathogens such as HIV-1 and, more recently, Ebola virus in West Africa and Zika virus in the Americas, demonstrate the need for a better understanding of when and where outbreaks emerge and what determines how viruses spread at different geographic scales. Unfortunately, incomplete genetic surveillance efforts and problems with the current generation of analysis tools make it difficult to provide accurate predictions that can anticipate the spread of disease. New digital mapping approaches offer high-resolution insights into disease transmission risk, but these do not use the information about virus transmission history that is contained in virus genome sequences.

I will develop a new framework – genetic cartography – that brings together genetic, spatial and mobility data in order to inform and aid disease outbreak control. The goals of this fellowship are to find out what determines virus spread at local, regional and global scales using datasets containing thousands of HIV, Ebola and Zika virus genome sequences. I will also develop realistic computational models of virus spread at a high-resolution spatial scale that will predict future virus spread and disease burden.

Dr Pawel Grzechnik

University of Birmingham

RNA Polymerase II CTD readers in gene expression regulation

Gene expression is the most strictly controlled process in a living cell. It involves transcription of genetic information encoded in DNA to RNA. This is followed by RNA processing or degradation. Any defect in this process may lead to developmental defects, ineffective stress responses, premature ageing, carcinogenesis and ultimately cell death.

In eukaryotic cells, major RNA metabolism regulatory mechanisms are mediated by the RNA Polymerase II C-terminal domain (CTD). Phosphorylation of CTD constitutes ‘the CTD code’, which is believed to define the recruitment of specific factors (‘CTD readers’) mediating all steps in the transcriptional cycle as well as RNA processing and degradation. In human cells, deregulations of processes mediated by CTD readers are directly associated with cancer and other genetic disorders. Although CTD readers have emerged as central players regulating nuclear RNA metabolism, their functions are still not fully uncovered.

My goal is to elucidate how these fundamental factors ‘police’ RNA by regulating the transcriptional cycle, transcription termination and the stress response. This knowledge will contribute to our understanding of fundamental processes facilitating normal cellular lifespan at the molecular level.

Dr Timotheus Halim

University of Cambridge

Immune-regulatory functions of group 2 innate lymphoid cells in cancer

Despite advances in cancer immunotherapy, there are still many unknowns that limit our ability to harness the power of the immune system to fight cancer.

My research will investigate the function of a recently discovered immune-regulatory cell called group 2 innate lymphocytes (ILC2), which I have shown to be critical for establishing a type of inflammation that promotes allergy and cancer formation. I found that these cells greatly increase during the course of tumour development in the pancreas. My research will leverage reagents that target ILC2 to determine their role in pancreatic cancer. This work may lead to new therapies that prevent the development of this disease. Moreover, we now understand that ILC2 are fundamental in allergies, and it is known that cancer patients with asthma are more likely to develop lung metastasis. My preliminary work suggests that ILC2 play a role in creating an immune environment in the lungs that helps the process of metastatic seeding. My proposed research will investigate the role of ILC2 in lung metastasis.

My findings could be used to help develop therapies to combat the spread of cancer.

Dr Zuzana Licenikova Horejsi

Queen Mary University of London

Identification of novel protein interactions within DNA damage pathways regulated by non-canonical and novel DNA damage kinases

Exposing DNA to agents such as UV light or products of cellular metabolism can result in damage, leading to mutations in the DNA, which can transform normal cells into tumours.

Normal cells are protected from these mutations by DNA damage repair (DDR) mechanisms. The DDR mechanisms are regulated by kinases – enzymes that modify other proteins through a process called phosphorylation. 

The kinases that mainly take part in DDR are called the canonical DDR kinases. The kinases that mainly regulate other cellular processes, but have some involvement in DDR, are called the non-canonical DDR kinases. Surprisingly little is known about the role of these non-canonical kinases in DDR.

My project aims to identify the novel protein-protein interactions within DDR which are dependent on phosphorylation carried out by the non-canonical kinases. It also aims to identify the kinases responsible for the phosphorylation. Ultimately, understanding how DNA damage repair is carried out and regulated will help identify and develop more efficient ways of treating cancer.

Dr Henrik Kløverpris

University College London

The role of innate lymphoid cells in the gut to understand HIV pathology

One important aspect of HIV infection is the direct impact on the gut. The gut barrier maintains separation between commensal bacteria and the host. HIV breaks down the ability of the gut to separate bacteria from entering the host. This results in activation of the immune system, which is the best predictor of time to AIDS. Even HIV patients under successful antiretroviral treatment have viral growth within their lymphoid organs and have elevated immune activation.

A component of the immune system, innate lymphoid cells (ILCs), has recently been discovered. ILCs are essential for the ability of the gut to prevent bacteria from entering the host system. We have shown that ILCs are eradicated from the blood of HIV-infected subjects during early stages of HIV infection.

The specific goal of this research is to understand the role of ILCs in the gut during HIV infection. I will use this information to understand the mechanism of gut break down and develop new treatment strategies to prevent AIDS.

Dr Anna Kuppuswamy

University College London

Psychophysics of predictive motor control: a novel model of post-stroke fatigue

Many stroke survivors complain of a tiredness or fatigue that is different from normal tiredness, and sometimes lasts for months or years. 

A key feature of this fatigue is the feeling of high effort while performing simple actions. Normally, performing simple actions feels effortless because the brain anticipates the sensation associated with force production in muscles and supresses these sensations.

My hypothesis is that the brain system that suppresses the sensations produced from simple movements is faulty in people with fatigue. This means that even simple movements feel effortful. As part of my research, I will temporarily improve the brain’s ability to suppress sensations and investigate if this alleviates fatigue. I will use a number of techniques, including electroencephalograph to record brain activity directly, self-reported questionnaires and brain stimulation techniques. The study will explore neurological fatigue from a completely new perspective and provide a potential therapy for fatigue.

Dr Hansong Ma

University of Cambridge

The genetics of the Drosophila mitochondrial DNA and its influence on evolution and disease

In addition to the nuclear genome, all animals have another genome packed inside the mitochondrion called mtDNA. This maternally inherited genome encodes important proteins for energy production. Mutations in mtDNA are responsible for over 50 mitochondrial diseases, affecting 1 in 4,300 of the UK population. 

Given that there are multiple copies of mtDNA in each cell, pathogenic mitochondrial mutations often arise among thousands of wild-type genomes. Once their percentage exceeds a certain threshold, it causes a phenotypic manifestation of the genetic defects. Selectivity in the transmission of functional versus pathogenic genomes in somatic cells affects the expression of disease phenotype as we age. Selective transmission in germline governs the inheritance of mtDNA mutations from mother to progeny, and in this way its evolution. 

I have developed some genetic tools for mitochondrial studies in Drosophila, which have a mitochondrial genome that is very similar to humans. By artificially mixing different genomes and following their transmission over generations, I will use Drosophila to investigate how mitochondrial mutations are inherited. I will also investigate how differences in mitochondrial genotypes contribute to broad-scale organismal phenotypes, such as longevity and fertility. These studies will advance our understanding of mitochondrial genetics and provide new insights into mitochondrial disease.

Dr Chris MacDonald

University of York

Mechanisms of cell surface recycling pathways

The cell surface is very important to the viability of a cell as it represents the barrier between the inside of the cell and the environment. Regulating what molecules are present at the cell surface is critical in determining how a cell interacts with its environment. To achieve this, surface proteins are continually internalised to ‘endosome’ compartments where proteins are physically separated into different categories such as those to be sent back to the surface or those to be kept inside. The recycling from endosomes back to the surface is dysregulated in cells taken from patients with diseases, including diabetes, cancers and cardiovascular disease. Despite its clear physiological importance, little is known about the machinery that regulates recycling.

By taking advantage of evolutionary conservation that exists between yeast and humans I have identified the responsible components of this trafficking pathway to the surface of the cell. I now propose specific ideas to investigate exactly how this machinery works. Human cells have a version of the proteins that I identified in yeast, so I will test their function in human cells using techniques developed by a collaborator.

Dr Naomi McGovern

University of Cambridge

Characterisation of the human extra-embryonic macrophage population, Hofbauer cells, phenotype and function

The human placenta is a major signalling organ that regulates the health of both the mother and developing fetus during pregnancy. The placenta is generally thought to consist of the maternal and the fetal side. While we have some understanding of the biology of maternal-derived immune cells in the placenta, our understanding of fetal-derived immune cells is still extremely poor. In particular, I am interested in studying fetal-derived macrophages in the placenta, commonly termed Hofbauer cells (HBC). HBC are thought to play a key role in placenta development and in defending the developing fetus from infection. However, we still have little understanding of how HBC do this. This is particularly relevant for pathogens such as Zika virus which seem to be able to cross the placenta from the mother to infect the fetus.

This study will help to develop better techniques to identify HBC and will highlight the importance of HBC in placenta development and demonstrate how they help protect the fetus from infection.

Dr Gemma Modinos

King's College London

Stress and GABA in the pathogenesis of psychosis

Psychosis is the fourth leading cause of disability in the world. The first symptoms, such as hearing voices that aren't there, appear in adolescence. These symptoms result from interactions between genes and environmental risk factors like stress. Current treatments do not work for about 50 per cent of patients, and have little impact on prevention.

Psychosis is associated with producing too much of the brain chemical dopamine, but little is known about what causes this. Research in experimental animals shows that problems in regulating the response to stress lead to deficits in another brain chemical called GABA. This produces an excess of dopamine in the brain. When adolescent rats are given a drug that improves GABA function, the response to stress is reduced. This prevents an excess of dopamine.

I will use neuroimaging to study the relationship between stress, GABA and psychosis in three related studies. These studies will involve the animal model, patients with psychosis, and people at high risk of the disorder. These studies will help us to use the stress response to identify people who are most at risk of psychosis, and new ways of preventing psychosis by reducing the response to stress.

Dr Katarzyna Modrzynska

University of Glasgow

Dissecting the transcription regulatory network in malaria parasites at early transmission stages

During its life cycle, the malaria parasite passes through a succession of over ten different life forms. These transitions involve extensive remodelling of the parasite cell and require changes in the expression of many genes. Recently a group of potential key regulators of this process called apicomplexa AP2 proteins (apiAP2) was discovered. The role of different members of this family across the life cycle remains to be investigated.

Here I propose to analyse the function of the apiAP2 genes during one of the major bottlenecks of the malaria life cycle - the initial stage of development in the mosquito. By identifying apiAP2 genes essential for this transition and analysing the function, I aim to construct a comprehensive model of this transition. 

Such a model would lead to a better understanding of the parasite biology, potentially leading to the development of new drugs.

Dr Ignacio Moraga

University of Dundee

Mapping cytokine signalling networks using engineered surrogate ligands

Cells sense their environment through surface molecules known as receptors. Engagement of these receptors by factors present in the cellular milieu triggers a series of molecular events inside the cells. This leads to activation of specific gene expression programs and modification of cellular responses. How environmental information is transmitted through these intracellular signalling wires remains one of the longest-standing questions in biology. Deregulation of this process often results in disease, making its molecular understanding very relevant for human health.

I propose to obtain a detailed characterisation of the components that form these intracellular wires and their dynamics in response to alterations in the environmental conditions. I plan to engineer soluble factors that are able to engage surface receptors with different binding topologies and alter the activation of intracellular signalling networks.

By combining these engineered factors with quantitative methodologies that allow the characterisation of the signalling state of a given cell in time, I will obtain a precise understanding of how the intracellular signalling networks are formed and shaped in response to cellular stress. I believe that this will translate into a better comprehension of the functional plasticity exhibited by cells and the development of more specific and less toxic therapies.

Dr Manuel Mueller

King's College London

Function of post-translational modifications of protein backbones in signalling and molecular ageing

The majority of tasks inside living cells are performed by tiny molecular machines, called proteins. Most proteins are regulated by chemical on/off switches. Malfunction of these switches can have disastrous consequences for the wellbeing of individual cells and entire organisms.

I am fascinated by a class of protein switches that respond to molecular wear and tear to signal for repair processes. However, investigating such processes is extremely challenging due to a lack of means to efficiently detect which of over 30,000 different proteins in a cell are affected by ageing, and our inability to age proteins in a controlled manner.

I propose to develop a suite of chemical biology technologies to illuminate how molecular wear and tear impacts senescence of cells and entire organisms. I will design molecular scalpels that precisely cut proteins only at sites of ablation. This will allow me to identify proteins that are susceptible to ageing. I will chemically install artificially aged components into otherwise young proteins and measure how old components affect the structure and function of molecular machines.

I aim to identify senescence sensors and delineate how they operate in healthy cells and might malfunction in diseases.

Dr Timothy Nott

University of Oxford

Compartmentalisation via liquid-liquid phase separation in cells

A central organising principle of eukaryotic cells is the compartmentalisation of biochemical reactions by membrane boundaries into organelles. However, not all processes are organised in this fashion. Organelles, such as nucleoli, Cajal bodies and P-granules are cellular compartments that lack a membrane boundary. Often spherical in appearance and readily observable with a light microscope, membraneless organelles are highly dynamic and can rapidly assemble and dissolve with changes to the cellular environment. They are predominantly associated with DNA and RNA processing, and have been linked with neurodegenerative diseases and viral infection. Membraneless compartments typically display the properties of liquid droplets. They form by the condensation of material in the cell, in a similar way to how water condenses to form rain drops. Their droplet-like nature makes membraneless organelles particularly challenging to work with and study.

By creating model membraneless organelles, I have shown that their interior is a unique solvent environment, geared towards making certain biochemical reactions involving DNA and RNA more efficient.

I propose to use an approach spanning physics and biology to explain how the liquid properties of membraneless organelles provide a general organising principle in cells, and to understand why cells perform certain reactions inside them.

Dr Daniel Neill

University of Liverpool

Identification of niche-specific virulence factors via experimental evolution of Streptococcus pneumoniae

The pneumococcus is a bacterium that causes severe diseases throughout the world, but particularly in poorer countries. It is the most common cause of death from infectious disease in children under five. We don't have a vaccine that protects against every type of pneumococcus, and what makes pneumococcus so deadly is the ability to adapt to different challenges in different sites in the human body. Many people have pneumococcus living harmlessly in their noses and mouths, but it is also able to survive in the lungs (where it can cause pneumonia) and the lining of the brain (where it causes meningitis).

This five-year project aims to explain how pneumococcus thrives in different places. By comparing the genes of bacteria that cause different types of disease I will be able to find out which genes are required to infect certain organs. I will then construct bacteria that lack these genes and find out if they are still able to cause disease. This will help us understand what changes in the ‘safe’ bacteria in our noses which allows them to cause disease. I aim to find important bacterial proteins that could be targeted in new vaccines or drugs that could control pneumococcal disease.

Dr Hanneke den Ouden

University of Cambridge

How to get things done: unravelling the neurobiology of adaptive decision-making

Our brains use at least two different ‘modes’ to make decisions. One mode is fast and almost automatic, but prone to mistakes. The other is more accurate, but takes a lot of time and mental effort. We don’t understand why, how and when we switch between these different modes. This is an important question because people who continuously try to achieve perfection have a high risk of burn-out. Perfectionism is also associated with psychiatric disorders like anxiety and depression.

We will investigate how people make imperfect decisions. We will analyse people’s brain activity while they perform various computer tasks in which they choose whether to use a ‘perfect’ or a ‘fast’ strategy. We will investigate how the brain chemicals dopamine and serotonin help to balance the costs and benefits of each strategy. Finally, we will ask people outside the lab to play our tasks online. Here we will investigate whether their task performance allows us to predict who can thrive in a work environment where there is no time to find a 100 per cent correct answer, and who might need a little help to avoid burn-out.

Dr Adam Packer

University of Oxford

All-optical interrogation of neural circuits during behaviour

Neurons in the brain process information via electrical impulses or spikes. How does the pattern of spikes drive perception or enable performance of an action? Despite substantial progress in neuroscience, these questions have yet to be answered.

I will reveal how brains work to perform computational feats. Previous research on how spikes drive behaviour has taken two complementary approaches: correlating neuronal activity with what is happening in the environment and stimulating neuronal activity while recording behavioural responses. The goal of my proposal is to bring these two approaches together. I have developed an optical approach that allows me to use light to both record and manipulate the activity of many neurons simultaneously on the level of individual spikes. I will employ this approach in the sensory cortex of a mouse performing sensory-guided tasks to manipulate neurons in a precisely targeted manner and examine the influence on behaviour to understand the ‘code’ the brain uses.

My findings may give us new insights into the workings of the neocortex and in turn spur development of new treatments for debilitating brain disorders.

Dr Lorenzo Pellis

University of Warwick

Epidemiological and evolutionary consequences of coinfection: a multi-scale modelling approach

Co-infections of multiple pathogens, such as HIV and tuberculosis, are a huge healthcare burden, worsening outcomes for patients and generating epidemics that fuel each other. Co-infections with multiple variants of the same pathogen can also be problematic: co-existence of drug-susceptible and drug-resistant strains can lead to treatment failure and cause resistance to spread among individuals.

The explosion in the amount of genetic data being generated has significantly improved our understanding of the complex processes occurring during co-infection. However, implications for population-level spread, and for the predicted impact of different control policies, remain difficult to assess. Specifically, there is a lack of suitably flexible mathematical models. I will develop novel modelling tools that can capture, in a unified framework, both detailed within-host processes and realistic features of epidemic spread. I will use this approach to study the spread of antimicrobial resistance; the evolution and spread of HIV; and the co-circulation of multiple pathogens. Importantly, I will assess the impact that co-infection has on predicted outcomes of different interventions.

This project will address one of the major modelling challenges that critically limits the predictive power of current models in epidemiology and evolutionary biology.

Dr Saravana Ramasamy

Imperial College London

Aetiology and consequences of vascular ageing in the skeletal system

Ageing is associated with a loss of bone density. This increases the risk of fractures and poor fracture repair, and other musculoskeletal disorders. Understanding the regulation of bone turnover to re-establish bone formation may lead to new strategies to treat bone loss and associated bone disorders. 

Blood vessels – collectively referred to as the vasculature – supply bone with oxygen and nutrients and provide cell surface or secreted signals that regulate skeletal tissue. Age-related changes in bone are associated with changes in the bone vasculature, but it is still largely unknown which physiological factors regulate these changes. 

My study will show blood flow to bone as a critical factor controlling blood vessel growth. The project aims to gain insights into the relationship between blood flow and the bone microenvironment using mice as a model system. I will use a combination of advanced high-resolution imaging, live animal imaging, mouse genetics and transcriptome analysis. The study has the potential to unravel key mechanisms behind bone ageing and identify novel therapeutic strategies for managing age-related bone and blood diseases.

Dr Aman Saleem

University College London

Transforming visual images into cognitive maps

Memory is a fundamental aspect of our selves, defining who we are and where we have been. The seemingly inevitable impairment of memory, due to pathologies such as Alzheimers disease, or normally during ageing, afflicts large segments of the population. Therefore, understanding how memories are created and used represents a major frontier of neuroscience research.

Spatial memory has been the subject of intense research. It is both the knowledge of an environment and sensing where we are while we navigate. How does the brain use external visual images to create an internal spatial memory for navigation? While brain regions involved in vision and memory have independently been the subjects of research, we do not know how they work together.

My goal is to understand how images of visual scenes are transformed into a spatial memory. To investigate this, I will take advantage of new experimental tools: rodent virtual-reality, large-scale electrical recordings and optogenetic interventions of neural circuits. I will investigate the circuits and computations that transform visual signals into spatial signals. I will also investigate how the hippocampus combines visual information with other inputs.

Dr Trevor Sweeney

University of Cambridge

Understanding the translation landscape at the host pathogen interface

When viruses infect a cell they often display structures that are sensed as foreign. After detection, signalling pathways result in the production of proteins called interferons. These proteins induce the production of hundreds of other proteins called interferon-stimulated genes in the infected and neighbouring cells to fend off the viral infection.

I have shown that the interferon-induced protein with tetratricopeptide repeats-1 (IFIT1) preferentially binds RNA with improperly processed ends and blocks the production of protein from this RNA. However, the role of IFIT1 in the antiviral response is still not clear since the only viruses affected by this RNA binding activity are those genetically engineered to be susceptible. There is also evidence to suggest that IFIT1 can bind fully processed RNAs. My hypothesis is that IFIT1 can interact with cellular RNA and that this interaction is important for the antiviral response. I will use multiple cutting-edge RNA/protein analysis approaches to determine what RNAs IFIT1 binds and their fate, how RNA binding regulates IFIT1 protein-protein interactions and what affect IFIT1 has on translation in the whole cell.

By understanding the impact of IFIT1 on the cell we will gain an insight into its role in the host antiviral response.

Dr Jack Wells

University College London

Imaging and activation of glymphatic clearance: a novel strategy for Alzheimer's disease

Despite the huge social, economic and emotional burden of Alzheimer’s disease, there is currently no cure. The development of effective treatments is hindered by the difficulty of accurately identifying the early phase of the disease, years before symptoms become apparent. Recent evidence has come to light from experiments performed in the rodent brain, of a previously unrecognised ‘waste removal’ system that clears excess fluid and toxins from the brain. It is thought that impairment of this pathway, known as the glymphatic system, may be a critical causal factor in the development of Alzheimer’s disease. However, currently this pathway cannot be measured in humans.

I will develop the first non-invasive method to image the glymphatic system using MRI, enabling assessment in the human brain for the first time. This method will be used to better understand how impairment of the glymphatic system contributes to Alzheimer’s disease and how this may be affected by the changes in properties of the brain’s blood vessels.

This proposal may lead to a new method for early detection of Alzheimer’s disease and identify a new target for effective drug treatment.

Dr Elton Zeqiraj

University of Leeds

Assembly, activation and function of JAMM/MPN deubiquitinating complexes

The small protein ubiquitin can alter the fate of a cell’s life. It is attached to other proteins as a tag that carries specific signals and important instructions. Enzymes that perform the protein tagging process (ubiquitylation) are called ligases and those that remove the ubiquitin tag are called deubiquitylases (DUBs). The cell has evolved in many ways to control the activity of DUBs because these are often mutated in cancer, neurodegeneration and autoimmune disease.

I’m interested in a specific DUB family called JAMM/MPN. These proteins often do not act alone, but interact and form large complexes with other regulatory proteins. I want to understand how one such DUB, BRCC36, forms large molecular machines and how it becomes active when the cell requires its services to remove ubiquitin tags. This is important because BRCC36 serves as a safeguard to ensure that immune signals are passed on to clear a viral infection. On other occasions, BRCC36 provides a sitting platform for proteins to repair a damaged strand of DNA.

An important aspect of my research is to identify small molecules that can help us understand how BRCC36 works and perhaps provide a starting point for future therapeutic agents.

2015

October

Dr Liam Browne

University College London

Functional dissection of neural circuitry underlying pain signalling

Liam is a neuroscientist who is interested in the fundamental mechanisms of nociception and pain. He uses advanced optical and genetic tools with electrophysiology to address how stimuli are encoded and processed by the spinal cord. During this Fellowship he aims to establish how specific cells guide protective behaviours and examine how these processes are transformed in disease.

Dr Rebecca Burton

University of Oxford

Optical interrogation of sub-cellular cardiac signalling in atrial and sino-atrial node arrhythmias at high spatiotemporal resolution

Rebecca is a physiologist with an interest in applying bioengineering methods to answer questions about causes and consequences of arrhythmias. Atrial fibrillation (AF) is the most frequently encountered arrhythmia, associated with increased morbidity and mortality. There are approximately 4.5 million Europeans suffering from AF. Research has suggested an important role for calcium dysregulation in AF. To improve our mechanistic understanding, Rebecca proposes a multidisciplinary approach, ranging from conventional electrophysiology to state-of-the-art tissue engineering and optogenetics and development of novel high-speed optical microscopy techniques. The results will allow a better understanding of the basic biological mechanisms of sub-cellular calcium signalling and the aetiology of AF directly relevant in the development of new treatment therapies.

Dr Helge Dorfmueller

University of Dundee

Functional and structural studies of the streptococcal virulence factor Group A carbohydrate biosynthesis pathway

Helge is a glycobiologist who focuses on exploring how carbohydrates are synthesised by the human-exclusive pathogen Streptococcus pyogenes. These bacteria cause common infections such as tonsillitis ('strep throat'). Importantly, mild infections can develop into life-threating diseases and current antibiotics are not sufficient to eradicate all mild and severe infections. Helge's research is aimed at uncovering the molecular mechanism underlying the biosynthesis of a novel bacterial virulence factor. He uses a multidisciplinary approach, combining molecular microbiology, enzymology, structural biology and inhibitor screening. This research forms the basis to ultimately develop inhibitors to prevent severe streptococcal infections in humans.

Dr Paul Fogg

University of York

Gene transfer agents: prevalence, biology and impact on bacterial genetic diversity

Rapid bacterial evolution is a major public health concern, and limiting the exchange of virulence or antimicrobial-resistant genes between bacteria is an acute challenge for modern medicine. Paul is interested in the molecular mechanisms of horizontal gene transfer, in particular gene transfer agents (GTAs). GTAs are unusual viruses of bacteria with the potential to move any gene from one bacterium to another at extraordinary frequencies, yet there are huge gaps in our knowledge of GTA biology. Paul's research aims to determine the fundamental mechanisms of GTA biology, their prevalence in pathogens and their impact on bacterial evolution.

Dr Ben Longdon

University of Exeter

The evolutionary and mechanistic basis of virus host shifts

Ben's research aims to understand what allows a virus to jump into a new host species and therefore potentially lead to the emergence of a new disease. Ben is based at the University of Exeter's Cornwall campus, where he uses insects and viruses as models to address fundamental questions about pathogen host shifts. He is investigating the factors that determine why viruses can infect some hosts but not others, and is examining how host adaptation and host range can affect the propensity of a virus to host shift.

Dr Andrew MacAskill

University College London

Encoding emotion in neural circuitry

Andrew's work aims to understand how different neurons in the brain communicate with each other to allow them to encode emotional behaviours. Problems with this communication underlie the vast majority of neurodegenerative and neuropsychiatric disorders, and so his aim is to find novel ways to combat these disorders by gaining a greater understanding of the processes that they destroy. To achieve this, Andrew uses a combination of in vivo and in vitro viral expression, two-photon microscopy, optogenetics, electrophysiology and behavioural assays to identify and characterise the synaptic, cellular and circuit mechanisms underlying the generation of emotional behaviour.

Dr Marta Polak

University of Southampton

Targeting human Langerhans cells to induce long-lasting tolerance in allergy

Marta is an immunologist interested in how immune responses to allergens are initiated and regulated in human skin. Allergy is a chronic disease that is expected to affect more than 40 per cent of all Europeans in 10 years' time. Recent studies demonstrate that skin can be successfully used as a gateway for therapeutic interventions aimed at improving the body's immune defences. Marta will combine high-power computing with extensive laboratory analysis of patient samples to answer two important questions: how does the skin allergy develop in early life, and how can we use transcutaneous therapy to deliver allergy treatment and prevention?

Dr Amy Saunders

University of Manchester

The role of CD200R1 signalling in regulating skin inflammation

Amy is an immunologist studying inflammatory skin diseases such as psoriasis. Her research investigates mechanisms that prevent a healthy skin immune system from responding to harmless environmental substances. Her hypothesis is that a failure of such regulatory mechanisms underlies inflammatory skin diseases. CD200R1 is a regulatory protein on the surface of many types of immune cells. Amy's work has shown that this protein plays an important role in regulating immune responses in skin and her current research aims to understand how this regulation occurs, and whether manipulating this protein represents a beneficial therapeutic strategy for inflammatory skin disease.

Dr Hayley Sharpe

University of Cambridge

Receptor tyrosine phosphatases in physiology and disease

Hayley is a cell biologist based at the Cambridge Institute for Medical Research. Her aim is to investigate the function and regulation of the receptor family of tyrosine phosphatases (RPTPs). Dysregulation of protein tyrosine phosphorylation is linked to developmental abnormalities and diseases such as cancer. Her research will focus on revealing the role of plasma membrane RPTPs in sensing the extracellular environment to influence cell behaviour. She uses genetics, functional proteomics and cell-based assays to reveal substrates and signalling pathways controlled by RPTPs in physiology and disease.

Dr Benjamin Steventon

University of Cambridge

Gene expression heterogeneity in the maintenance and coordinated differentiation of neuromesodermal progenitors in vivo

Ben is interested in how the embryo develops from a round ball of cells into an elongated body axis. In vertebrates, stem cells called neuromesodermal progenitors continually self-renew and differentiate to provide a continued source of spinal cord and muscle progenitor cells. How the processes of self-renewal and differentiation are precisely balanced during development and growth is an essential question in biology. Ben aims to understand the mechanisms that control this balance by studying the dynamics of neuromesodermal cells across a range of organisms that display differences in the amount of growth which occurs together with axis elongation.

Dr Lucy Weinert

University of Cambridge

Investigating the link between genome reduction and pathogenicity using an emerging zoonotic pathogen

Lucy is an evolutionary biologist whose research aims to understand why and how bacteria become pathogens. One longstanding observation is that bacterial pathogens often have smaller genomes and fewer genes than their nearest non-pathogenic relatives. Using the bacterium Streptococcus suis as a model system, Lucy's laboratory will sample whole genomes of global populations, develop new statistical models and collate functional data in order to conduct the first large-scale tests of the various hypotheses linking genome reduction and pathogenicity. The long-term goals of this research are to forecast pathogen emergence, to develop preventative strategies, and to improve treatments.

May

Dr Krishnan Bhaskaran

London School of Hygiene and Tropical Medicine

BEYOND cancer: using big data to identify opportunities for cardiovascular disease prevention after cancer

Krishnan is a statistical epidemiologist interested in harnessing large-scale electronic healthcare data to answer questions about causes and consequences of cancer. There are more than 2 million cancer survivors in the UK and tens of millions worldwide. The long-term cardiovascular health of these individuals is of concern, given potential cardiotoxicities of cancer treatments. Krishnan aims to bring together multiple 'big data' sources containing information on cancer diagnoses and treatments and long-term health outcomes. He will quantify excess risks of cardiovascular diseases among cancer survivors, develop prediction tools to identify those at highest risk, and investigate opportunities for better use of preventative therapies.

Dr Thomas Clarke

Imperial College London

Defining the members of the microbiota that regulate systemic immunity and promote host resistance to infection

Thomas's research aims to determine how the microbiota regulates the immune system and how this promotes host resistance to infection. Multicellular organisms are colonised by large communities of symbiotic bacteria (the microbiota), which are a major regulator of host immunity. Microbiota disruption has been linked to diseases and conditions including cancer, autoimmunity, and reduced host defence to infection. Thomas is aiming to decipher the language of communication between the immune system and microbiota, which is currently poorly understood. The goal of this is to harness the power of the microbiota as a novel way to combat infections.

Dr Jesmond Dalli

Queen Mary, University of London

Statin-triggered novel resolvins as innovative resolution-based therapeutics in arthritis

Jesmond's research efforts are focused on the structural elucidation of omega-3 fatty acid-derived bioactive mediators, assessing their cellular targets and the molecular mechanisms they activate in the resolution of inflammation. Of particular interest is a new family of mediators that he has identified and termed thirteen series resolvins. These mediators potently regulate the immune response limiting unwanted side effects. Jesmond's aim is to determine how the production of these protective molecules becomes dysregulated in chronic inflammatory diseases such as rheumatoid arthritis. Additionally, he aims to develop ways to replenish their endogenous levels as well as to use these molecules as biotemplates for the development of new therapeutics.

Dr Rhian Daniel

London School of Hygiene and Tropical Medicine

Statistical methods for studying multidimensional mediators of genetic associations with chronic diseases

Rhian is a statistician with a particular interest in methods for making inferences about cause-effect relationships. Recent advances in omics technologies, which have dramatically changed the nature and scale of observational data, require corresponding developments in statistical methods in order to make sense of this new wealth of information. By focusing on methods for causal mediation analysis and extending them to handle the dimensionality and complexity of proteomic and metabolomic mediators, Rhian aims to be able to answer questions such as: which of the metabolic subtypes of LDL cholesterol lie on the strongest causal pathways from established CVD genes to disease?

Dr Chiara Francavilla

University of Manchester

Exploring how endocytic recycling of receptor tyrosine kinases specifies cellular responses

Chiara is a cell biologist who focuses on exploring how the trafficking of receptor tyrosine kinases (RTKs) from and to the plasma membrane can elicit specific cellular responses. She uses functional proteomics, which integrates quantitative mass-spectrometry-based proteomics, bioinformatics analysis, functional assays and imaging techniques. Her research is aimed at uncovering the molecular mechanisms underlying the intracellular trafficking of RTKs, resultant signalling specificity, and downstream outputs during development and cancer progression. The final goal is to identify and characterise proteins with key roles in RTK signalling and trafficking that can be targeted for intervention in human diseases.

Dr Christos Gkogkas

University of Edinburgh

Translational control of neuronal mRNAs in autism spectrum disorders

Christos is a molecular neurobiologist based at the Centre for Integrative Physiology and the Patrick Wild Centre at the University of Edinburgh. His research focuses on determining how regulation of gene expression, at the level of protein synthesis, in different neuronal cell types can impinge upon neurodevelopmental and neuropsychiatric disorders, such as autism spectrum disorder (ASD). Christos's group applies diverse biochemical and electrophysiological imaging and behavioural approaches in transgenic rodents to elucidate the neurobiological basis of 'autism-like' phenotypes. By studying the neurobiological underpinnings of ASD, Christos aims to identify novel therapeutic avenues for ASD.

Dr Joe Grove

University College London

Characterising viral antibody evasion by conformational masking

For a virus to maintain infection it must spread from one cell to another. Our immune system produces antibodies that bind to viruses and prevent this. However, viruses have evolved strategies to evade antibodies, allowing them to prevail despite our immune response. Joe is investigating conformational masking – an evasion strategy that essentially cloaks viruses from recognition by antibodies. He is using basic virology, patient samples and super-resolution microscopy to study conformational masking by hepatitis C and HIV. Through an understanding of such immune countermeasures we may be able to design therapeutic or vaccine-based interventions that empower the human immune response.

Dr Svetlana Khoronenkova

University of Cambridge

Signalling of DNA single-strand breaks and links to neurodegeneration

Svetlana is a biochemist with interests in DNA damage signalling and repair, also known as the DNA damage response. The cellular response to DNA damage is crucial in living cells that need to repair thousands of DNA lesions each day. The majority of these lesions arise from the intrinsic chemical instability of DNA, and defects in repair lead to human diseases such as cancers and neurodegeneration. Svetlana will use a wide variety of biochemical and molecular biological techniques to expand our understanding of the links between deficiencies in the DNA damage response and the molecular nature of progressive neurological diseases.

Dr Elisa Laurenti

University of Cambridge

Characterisation of inflammation-driven responses in human haematopoietic stem and progenitor cells

Elisa is a molecular and cellular biologist who studies how blood is formed in humans. Her main focus is to understand the molecular regulation of haematopoietic stem cells, the cells responsible for the continuous production of blood throughout a lifetime. After having described the molecular circuitry of these cells in normal steady-state conditions, she now aims to determine how they react to stress, in particular to inflammation. Determining which inflammatory signals act directly on human haematopoietic stem cells, and how, will be important for developing new therapies aimed at palliating the impaired blood production seen in chronic inflammation.

Dr Joo-Hyeon Lee

University of Cambridge

Regulatory signalling networks between stem and niche cells in lung regeneration

Joo-Hyeon's research aims to understand the interplay between stem and niche cells for lineage specification of adult stem cells in normal and diseased lungs. Signalling between stem cells and stromal cells is essential for organogenesis and adult tissue maintenance, but is poorly understood in the context of lung repair and regeneration. She will focus on identifying the key stem-stromal cell interactions and regulatory networks that allow for proper lung cell differentiation and injury repair using in vivo genetic mouse models and an in vitro organoid co-culture system that she has developed. This work will shed light on the repair mechanisms responding to regional damages along the pulmonary axis.

Dr Katrina Lythgoe

University of Oxford

From molecules to pandemics: multi-level adaptation of human chronic viruses

Katrina works on the evolutionary epidemiology of chronic viral infections such as HIV and hepatitis C. She is particularly interested in disentangling the often-conflicting selection pressures that occur at the within- and among-host scales, and how these pressures impact the evolution of these viruses in the face of different intervention strategies. She uses a range of methods including mathematical modelling, stochastic simulations, and the analysis of deep-sequencing data. Previously, Katrina held a Wellcome Trust Career Re-entry Fellowship, and prior to her return to research she was the Editor of Trends in Ecology & Evolution for seven years.

Dr Sara Macias-Ribela

University of Edinburgh

Antiviral defence mechanisms: small RNAs versus interferon pathway

Sara is an RNA biologist who focuses on understanding the control of the innate immune response in mammalian cells, particularly the cellular responses to dsRNA, which is a common intermediate of viral replication. Sara's main interests are to understand from the molecular and cellular level how differentiated and pluripotent cells employ different mechanisms to fight viral infections. These different cellular models will be used to study the cross-talk between the interferon and the small RNA pathway as two alternative antiviral mechanisms.

Dr Tom McAdams

King's College London

Elucidating the aetiology of psychopathology: taking a multigenerational approach to genetically informative data

Tom's research falls into the fields of developmental psychopathology, quantitative genetics, and psychiatric epidemiology. He is interested in the use of genetically informative datasets to understand the intergenerational transmission of psychopathology – how and why mental health problems run in families. Previously Tom has used children-of-twins datasets to study the impact of parental depression and anxiety on child emotional development. During his Fellowship Tom will be further developing the statistical models used to analyse such data. He will also extend his work into population databases and multigenerational genomic datasets in order to better understand the mechanisms underlying intergenerational transmission.

Dr Maike de la Roche

University of Cambridge

Hedgehog signalling in T cell effector and memory function in vivo

Maike is a vet and immunologist based at the Cancer Research UK Cambridge Institute. She is interested in CD8 T cells, which protect the body against infection with intracellular pathogens and tumours. Maike's research aims to elucidate the role of the developmental Hedgehog signalling pathway in CD8 T-cell effector and memory cell differentiation, maintenance and function during infection and tumorigenesis. Advances in this field will greatly benefit therapeutic approaches against infection as well as immunotherapy in cancer patients.

Dr Philip Spence

University of Edinburgh

Monocyte and macrophage function in malaria disease severity

Phil is a malariologist who wants to understand how children acquire immunity to severe malaria early in life. Resistance to severe disease is frequently observed after just one or two infections, and does not correlate with a child's ability to control parasite density. Immunity to severe malaria is therefore an acquired mechanism of disease tolerance. Phil's group at the University of Edinburgh are asking whether malaria can rewire the innate immune system to reduce inflammation and generate disease resistance. By studying mechanisms of innate immunity to malaria, the group aim to develop novel anti-disease vaccines.

Dr Bernhard Staresina

University of Birmingham

Episodic memory during offline periods

Bernhard's research focuses on episodic memory, our intriguing ability to mentally travel back in time and re-experience past events and experiences in great detail. Situated at the interface of neuroscience and experimental psychology, Bernhard uses functional neuroimaging in conjunction with electrophysiological recording techniques such as intracranial electroencephalography to elucidate the neural mechanisms underlying episodic memory formation and retrieval. Bernhard’s current projects aim to better understand how the brain solidifies previous experiences while we sleep. Gaining experimental control over such 'offline periods' holds great promise for opening a new window to targeted memory enhancement and therapeutic intervention.

Dr Timothy Witney

University College London

Detecting tumour resistance to treatment with positron emission tomography

Tim's research focuses on the discovery and development of novel imaging methods to measure tumour resistance to therapy. The majority of cancer deaths result from ineffective treatment of metastatic disease due to either acquired or innate resistance to anti-cancer drugs. There is therefore an urgent unmet clinical need to develop biomarkers that can sensitively detect resistance to therapy early in a patient's treatment cycle. The early detection of treatment failure by noninvasive imaging will hopefully enable the selection of different drugs and more effective treatments, with the potential to substantially improve outcomes in this disease.

Dr Tzviya Zeev-Ben-Mordehai

University of Oxford

Molecular understanding of protein-mediated cell-cell fusion in fertilisation, development and viral spread using structural hybrid approach

Tzviya is a structural biologist interested in proteins that mediate the merging of membranes. Membrane fusion is a central process for all eukaryotic cells. Extracellular fusion that is cell-cell fusion is a crucial step in the initiation and development of multicellular organisms as well as maintaining homeostasis. Tzviya's project objective is an integrative structural characterisation of cell-cell fusion. The core technique to be applied is cryo-electron microscopy complemented by super-resolution fluorescence microscopy and crystallography. Her study aims to pave the way for molecular intervention in plasma membrane fusion, eg for designing new infertility treatments and contraception.

2014

Dr Maria Alcolea

University of Cambridge

Stem cell fate and plasticity in oesophageal wound healing

Maria is a cell biologist who focuses on understanding the behaviour of epithelial stem and progenitor cells. She uses the mouse oesophagus as a model to unveil the basic rules governing cell fate. Maria's work in the field has revealed how normal cell behaviour is drastically altered in response to injury. More recently she has shown how progenitor cells alter and adapt their dynamics as a result of pre-carcinogenic mutations, reflecting a remarkable epithelial plasticity. Maria’s main interests are in investigating the cellular and molecular mechanisms underlying this plastic cell behaviour, and the potential implications for early cancer development.

Dr Oliver Bannard

University of Oxford

Exploring how the germinal centre cellular programme promotes efficient affinity maturation

Oliver is a cellular immunologist based at the Weatherall Institute of Molecular Medicine at the University of Oxford. His research is aimed at determining some of the biological mechanisms employed by germinal centre B cells for promoting efficient antibody affinity maturation. Germinal centres are highly-dynamic, tightly-regulated environments in which B cells repeatedly mutate their immunoglobulin genes and undergo selection based upon the encoded membrane antibody’s ability to bind and capture antigen. Oliver aims to learn how these processes are controlled. It is hoped that advances in this field will facilitate the rational design of better vaccines and immunotherapies.

Dr Jimena Berni

University of Cambridge

Hox genes and the diversification of neuronal circuits

Jimena's research focuses on the general area of developmental neuroscience. In particular she investigates the relationship between neuronal circuits and behaviour, with emphasis on the diversification of circuits that control region-specific movements along the body axis. Specifically, Jimena studies the role of evolutionarily conserved Hox genes in specifying different neuronal networks and their assembly during development. This work will shed light on the mechanism and processes that generate regional specialisation of structure and function in the central nervous system.

Dr Kok-Lung (Chris) Chan

University of Sussex

Molecular basis of inheritable DNA lesions on genome transformation

Chris is a cell biologist whose group is based in the MRC Genome Damage and Stability Centre at the University of Sussex. His research focuses on understanding how genome integrity is maintained and restored under replication stress. Replication stress not only causes DNA damage during replication but also interferes with the timely completion of replication, which may result in the transmission of damaged genetic material into offspring cells. His main goal is to elucidate the mechanism(s) of genome rearrangements caused by replication stress induced DNA lesions, and ultimately develop preventative medicine and targeting therapy for cancers.

Dr Maria Christophorou

University of Edinburgh

Protein citrullination in cell physiology and disease

Maria is a biomedical scientist who has previously worked on tumour suppression, pluripotency and chromatin biology. She is interested in understanding protein regulation by post-translational modification, and her current research focuses on citrullination, a poorly-studied post-translational amino acid conversion. Abnormal citrullination is a pathological feature of diseases such as autoimmunity, neurodegeneration and cancer. Maria is using her Fellowship to set up an independent laboratory at the MRC Institute of Genetics and Molecular Medicine to study the molecular events that control citrullination, how it modulates protein function, and its impact on cell physiology and disease.

Dr Paul Conduit

University of Cambridge

Investigating the spatiotemporal regulation of microtubule nucleation in Drosophila

Paul is a cell biologist based in the Department of Zoology at the University of Cambridge, who wants to understand how microtubule formation is regulated in space and time. Microtubules are polarised polymers that have a wide range of important roles in cells, including organising and transporting intracellular particles, vesicles and organelles, and separating duplicated chromosomes during mitosis. Paul uses a combination of Drosophila genetics and live cell imaging to study microtubule formation at different microtubule organising centres (MTOCs) in different cell types. He aims to determine how MTOCs form and how they recruit the protein complexes required to catalyse microtubule formation.

Dr Julia Cordero

University of Glasgow

Regulation of stem cell function during tissue homeostasis and transformation

Julia is a developmental biologist and geneticist who combines work on the fruit fly Drosophila melanogaster and mammalian model systems to understand the regulation of stem cells during tissue homeostasis and transformation. Using the adult Drosophila midgut, Julia wants to understand how cell-autonomous and niche-derived signals integrate to regulate stem cell proliferation in response to damage, as well as during tumorigenesis of adult self-renewing epithelia. By translating results from the fly into suitable mammalian paradigms, Julia aims to identify conserved mechanisms involved in the regulation of tissue homeostasis, which will be of broad benefit to our understanding of human health and disease.

Dr Rebecca Corrigan

University of Sheffield

Functional characterisation of (p)ppGpp in Staphylococcus aureus: essential messengers required for stress adaption and survival

Rebecca is a molecular microbiologist interested in the study of the cell-signalling and virulence mechanisms of the Gram-positive pathogen Staphylococcus aureus. Her recent work has led to the development of a genome-wide approach to analyse nucleotide-protein interactions. Rebecca aims to use this methodology, in conjunction with biochemical assays, to identify binding targets for (p)ppGpp, nucleotides that are involved in promoting persistent and recurrent infections. The mapping of the (p)ppGpp signalling network will provide a greater understanding of how S. aureus can persist in the human host, enabling rational drug design.

Dr Nick Croucher

Imperial College London

Evolutionary dynamics underlying pneumococcal genomic diversity

Nick is a microbiologist interested in pneumococcus, a bacterium usually harmlessly carried in the nasopharynx of many children that is also a common cause of pneumonia, sepsis and meningitis in infants and the elderly. These bacteria vary extensively in the frequency with which they cause disease and their susceptibility to antibiotics and vaccine-induced immunity. Nick's project aims to understand the evolutionary processes that create this diversity through combining information from genomics, molecular microbiology and mathematical modelling. The ultimate goal is to understand how bacterial pathogens are likely to respond to changes in the way we treat or prevent disease.

Dr Owen Davies

Newcastle University

The molecular structure and function of the human synaptonemal complex in meiosis

Owen's research aims to uncover the molecular basis of chromosome synapsis and genetic exchange during mammalian meiosis. In the first meiotic division, homologous chromosome pairs are 'zipped' tightly together along their entire length by the synaptonemal complex, a large protein assembly that provides the three-dimensional framework for meiotic recombination and crossing over. Through a biochemical and structural biology approach, Owen aims to solve the molecular structure of the synaptonemal complex and establish how it interacts with and directs the recombination machinery. This work will reveal the molecular details of meiotic chromosome synapsis and crossing over, and ultimately how defects in these processes lead to infertility, miscarriage and aneuploidy.

Dr Philip Elks

University of Sheffield

Manipulation of host hypoxia signalling as a therapeutic strategy for mycobacterial infection

Phil's research aims to understand the host innate immune response to mycobacterial infection (the causative bacteria of tuberculosis), in order to identify novel therapeutic strategies that may be effective against emerging drug-resistant strains. Specifically, he has focused on host-derived hypoxia signalling and has demonstrated that manipulation of this signalling system can help the host tackle infection. His lab uses a zebrafish model of mycobacterial infection to gain in vivo insights into the underlying mechanisms of hypoxia signalling regulation during infection. Phil's goal is to determine whether targeting hypoxia signalling could be used as an effective future TB therapy.

Dr Sarah Flanagan

University of Exeter

Applying the power of genetics to increase knowledge of underlying mechanisms of recessively-inherited congenital hyperinsulinism

Sarah is a molecular geneticist whose research focuses on monogenic disorders of insulin secretion. Her primary interest is in understanding the genetic basis of congenital hyperinsulinism, a severe, potentially devastating disorder characterised by the inappropriate secretion of insulin despite hypoglycaemia. Using a combination of homozygosity mapping studies and next-generation sequencing, Sarah aims to identify novel disease genes for congenital hyperinsulinism in the 60 per cent of patients currently without a genetic diagnosis. Understanding the underlying mechanisms of this disease will provide vital novel insights into beta-cell physiology and insulin secretion.

Dr Rachel Freathy

University of Exeter

Using genetics to understand how the maternal intrauterine environment influences fetal growth

Rachel aims to understand why some babies grow very large in utero while others are born very small. Her research uses information on genetic variations in large studies of mothers and their babies to separate true causal effects of the maternal environment from mere correlations. A better understanding of the factors that influence birth weight should enable targeted intervention to improve pregnancy management for healthy fetal growth.

Dr Elizabeth Fullam

University of Warwick

Understanding the role of sugar transporters in Mycobacterium tuberculosis

Liz is currently working in the School of Life Sciences at the University of Warwick. Her research focuses on understanding nutrient uptake and metabolism in Mycobacterium tuberculosis with the hope that this will lead to the development of novel therapeutic or diagnostic strategies. To achieve this, her lab is bringing together a range of biochemical, chemical and genetic approaches to determine the molecular mechanisms involved in the transport processes of essential nutrients by this pathogenic organism.

Dr Matthew Gold

University College London

Local cyclic AMP signalling in synaptic plasticity

Matthew is a structural neurobiologist who is interested in understanding how second messengers control changes in synaptic connections between neurons that are fundamental to learning. Second messengers, including cyclic AMP, can alter synaptic strength in different ways within a single neuron depending on the primary stimulus. Matthew's laboratory uses methods from structural biology, synthetic biology and electrophysiology to understand how neuronal proteins are organised at the molecular level to respond to local rises in second messengers. In this way, his laboratory aims to fill fundamental gaps in knowledge at a molecular level that is informative for pharmaceutical development.

Dr John Grainger

University of Manchester

Understanding the role and consequences of systemic monocyte conditioning during infection

John is an immunologist interested in mechanisms regulating inflammatory cells, in particular monocytes. Based at the Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, his group uses disease models alongside patient samples to explore inflammatory cell education during infection. Recently John’s work has focused on understanding how signals from the gut and lung instruct developing monocytes in the bone marrow following pathogen challenge and the consequences of this ‘systemic’ training. By identifying novel factors involved in this dialogue John aims to identify targets to modulate aberrantly activated inflammatory cells in chronic diseases such as inflammatory bowel diseases (IBD) or allergies.

Dr Matthew Hepworth

University of Manchester

Innate immune regulation of pathologic CD4+ T-cell responses in inflammatory disease

Matt is an immunologist who aims to understand how inflammation and immunity are orchestrated at mucosal barrier sites such as the gastrointestinal tract and lung. At the University of Manchester his group uses disease models and patient-derived samples to determine how a rare population of immune cells, known as innate lymphoid cells, act to control the magnitude of inflammatory immune responses towards foreign organisms and allergens. A greater understanding of how innate immune pathways regulate inflammation at mucosal barrier sites will inform the development of novel therapeutics to treat chronic human diseases such as inflammatory bowel disease and asthma.

Dr Clare Howarth

University of Sheffield

The role of astrocytes in neurovascular coupling in health and ageing

Clare is a neuroscientist with an interest in neurovascular coupling. It is critical for normal brain function that neural energy demands are met. Neural activity leads to a local increase in cerebral blood flow, a relationship termed neurovascular coupling. The mechanisms underlying this relationship are incompletely understood but involve many cell types including neurons, glia, and vascular cells. Based at the University of Sheffield, Clare's laboratory uses imaging techniques ranging from the cellular level (multiphoton laser-scanning microscopy) to the whole brain (fMRI) to investigate how astrocytes are involved in neurovascular coupling and how this relationship changes in ageing.

Dr Meritxell Huch

University of Cambridge

Understanding the molecular mechanisms of adult live regeneration

Meritxell is a stem cell biologist with a background in cancer and tissue regeneration. Stem cells are required for tissue homeostasis and tissue repair. At the Gurdon Institute, University of Cambridge, Meritxell and her team are focused on gaining further understanding of the molecular mechanism by which stem cells sense tissue damage and start proliferating to repair the injured tissue. By gaining further insight into these repair mechanisms, Meritxell aims to better understand the basics of cancer, because during tumour initiation, similar processes have to be activated to instruct the resting cells to start proliferating.

Dr Daniel Lawson

University of Bristol

Statistical methodology for population genetics inference from massive datasets with applications in epidemiology

Daniel's research focuses on problems arising from the volume of genetics data currently available. He uses and develops tools in statistics and machine learning to apply powerful genetics models at scale. His research examines population structure and its interaction with genomic selection. This provides insight into both the genetic history of people and the functional roles that genes may play in populations experiencing different environments. His research helps us to understand the information provided by massive-scale analyses, such as genome-wide association studies, as well as trying to identify genetic variants causing disease.

Dr Gloria Lopez-Castejon

University of Manchester

How regulation of deubiquitination by danger signals modulates and orchestrates inflammasome activation

Gloria is a molecular immunologist studying fundamental mechanisms of inflammation. Her group is based at the Manchester Collaborative Centre for Inflammation Research and she is interested in the regulation of the inflammasome, a molecular complex required for the release of potent pro-inflammatory mediators, such as interleukin-1β. Her research investigates the relationship between danger signals, deubiquitinases (DUBs) and inflammasome activation in macrophages to establish novel roles for DUBs in the inflammatory process and, consequently, in inflammatory pathologies.

Dr Tamar Makin

University of Oxford

Pushing the boundaries of human brain plasticity through sensory deprivation and learning

Tamar is based at the FMRIB, the University of Oxford’s neuroimaging centre. Her ultimate aim is to characterise and extend the boundaries of plasticity in the adult human brain, by combining experimental approaches from neuroscience, experimental psychology and rehabilitation. Her work addresses both scientific and clinical needs to better understand the relationship between two drivers of brain plasticity: input loss and altered behaviour. Her main clinical model is arm amputation, which introduces sensory deprivation, adaptive motor behaviour and phantom pain. Based on her experimental work, Tamar hopes to harness these drivers to enhance adaptive plasticity and reverse maladaptive processes in the clinic.

Dr Victoria Male

University College London

Natural killer cell subsets in the liver: phenotype, function and role in obesity-induced liver disease

Victoria is an immunologist who is interested in the development and functions of natural killer (NK) cells and their relatives. A special subset of liver-specific NK cells has recently been identified in mice. Victoria aims to investigate whether these cells are also present in the human liver, and to determine their functions in health and disease. In particular, she is interested in whether they have a role in the development and progression of the obesity-associated liver disease non-alcoholic steatohepatitis, which is thought to affect as many as five per cent of adults in the UK.

Dr Emily Osterweil

University of Edinburgh

Differential regulation of protein synthesis in synaptic plasticity and autism spectrum disorders with associated intellectual disability

Emily is a cellular neuroscientist interested in understanding how neurons use de novo protein synthesis to alter the strength of individual synapses. Her work is focused on isolating specific mRNAs that are newly translated in response to synaptic stimulation, in part using newly developed TRAP and RNA-seq technologies. She also investigates the interplay between the ERK and mTOR signalling pathways, which function in translation control. Emily's goal is to understand how the synthesis of new proteins supports both the strengthening and weakening of synapses, and how this goes awry in autism-linked neurodevelopmental disorders.

Dr Bryn Owen

Imperial College London

Female infertility: deciphering the mechanisms that perturb ERa signalling in the hypothalamus

Bryn is a molecular endocrinologist with training in nuclear hormone receptor signalling and the hypothalamic pathways that govern female reproductive function. Using model systems, he is investigating how the cellular receptor for oestrogen controls the timing and progression of the ovulatory cycle. He is also interested in understanding how this control is lost during nutritional challenges such as obesity and anorexia. Ultimately, Bryn aims to identify novel therapeutic targets for the treatment of metabolic sub-fertility in women.

Dr Ede Rancz

The Francis Crick Institute

Visuo-spatial processing in retrosplenial cortex

Ede is a neuroscientist with a background in synaptic physiology, single-cell computation and systems-level sensory processing. His laboratory focuses on the retrosplenial cortex of mice using in vivo patch clamping, calcium imaging, rabies-based connectivity mapping and behavioural techniques aiming to elucidate how internally generated models interact with external sensory stimuli to guide behaviour.

Dr Anthony Roberts

Birkbeck, University of London

Mechanisms and decisions in microtubule-based intracellular transport

Anthony's research focuses on the action of motor proteins; specialised proteins that travel inside cells and help them organise their contents, move, divide and respond to signals. His group within the Institute of Structural and Molecular Biology at Birkbeck/University College London uses structural biology and single-molecule techniques to ask mechanistic questions, such as: how do motor proteins move? How are they regulated in living cells? How and why does their malfunction give rise to human diseases such as neurodegeneration?

Dr Rahul Roychoudhuri

Babraham Institute

Regulation of immune function by the transcription factor BACH2

Rahul's research aims to understand how a class of proteins called transcription factors guide the behaviour of T lymphocytes. T lymphocytes powerfully regulate immune function by differentiating into specialised cellular lineages that either drive or constrain immune reactions. Based at the Babraham Institute in Cambridge, Rahul’s group applies diverse molecular biology, cellular immunology and functional genomics approaches to investigate how transcription factors regulate lymphocyte behaviour in the context of infections, autoimmunity and cancer. This research aims to identify targets for a new class of therapies that will powerfully manipulate immune function in patients with autoimmunity, chronic infection and cancer.

Dr Jerome Sallet

University of Oxford

Neuroethology of social decisions in primates

Jerome is a cognitive neuroscientist with a background in electrophysiology, neuroanatomy and neuroimaging. Through the complementarity of these techniques he is studying the structure and function of neuronal circuits supporting decision process. His current research looks more specifically at how social information is learned and encoded in the brain - from the neuronal level to the network level - to guide our behaviour. Understanding the role that neural circuits play in normal social cognition will not only inform theories in neuroscience, but will be an essential step to discover the neural mechanisms underlying disorders characterised by alteration of socio-cognitive processes.

Dr Philipp Voigt

University of Edinburgh

Roles of symmetric and asymmetric histone H3 lysine 27 trimethylation in gene repression and epigenetic inheritance

Philipp is a biochemist and cell biologist who is interested in understanding how post-translational modifications of histone proteins regulate gene expression. His research particularly focuses on the molecular mechanisms of the repressive histone mark H3 lysine 27 methylation. By combining biochemical and microscopy-based approaches, his lab aims to determine how this mark controls the expression of developmental genes in embryonic stem cells and to clarify whether this mark can serve as an epigenetic signal that can pass on information to daughter cells.

2013

Dr Caswell Barry

University College London

Role of novelty and uncertainty in memory formation: neural mechanisms

Caswell is a neuroscientist whose goal is to build a computational understanding of the neural basis of memory. This will entail explaining how a network of neurons is able to store, update and retrieve information about the world and events that happen within it. To this end, Caswell studies spatial memory and its representation in the hippocampal formation. His lab uses tools such as computational modelling and optogenetic manipulations to understand how the processes of memory formation and retrieval are triggered.

Dr Isaac Bianco

University College London

From vision to action: systems analysis of sensorimotor circuitry controlling visually guided behaviour

Isaac started his research group in the Department of Neuroscience, Physiology and Pharmacology at UCL in 2013. He is interested in understanding the neural basis of behaviour and his research combines two-photon functional imaging of neural activity with manipulation through optogenetic techniques. In addition, quantitative behavioural assays in larval zebrafish are used to investigate the structure and function of complete sensorimotor circuits.

Dr Miguel Branco

Queen Mary, University of London

Epigenetic control of retrotransposable elements

Miguel is interested in epigenetic mechanisms that regulate genome function and are implicated in cell identity, development and disease. He is currently investigating the role of different DNA modifications in the regulation of transposable elements. Using current and novel epigenomic technologies combined with molecular biology and genetic approaches, he aims to functionally dissect the epigenetic influence that these abundant genomic elements exert on gene expression and how they contribute to phenotypic variability.

Dr Filipe Cabreiro

University College London

Exploring the gut microbial action of metformin: targeting the gut microbiota to treat metabolic disease

Filipe is a biochemist with a background in exploring the biological mechanisms underlying molecular stress protection and ageing. Recently he has pioneered the use of the model organism Caenorhabditis elegans to study how drug-microbiota interactions affect host metabolism and ageing. This work has led to a focus on host-microbiota interactions and metabolic disorders. Using a combination of metagenomics and gnotobiotics, his research seeks to gain insight into the gut microbial action of drugs in higher organisms and to develop strategies for targeting the gut microbiota to treat host metabolic disease.

Dr Alan Cheung

University College London

Molecular mechanisms of transcriptional activation

Alan is a structural biologist interested in the fundamental mechanisms of gene transcription and how those mechanisms are used to control mRNA expression in eukaryotes. His group is based at the joint Institute of Structural and Molecular Biology at UCL and Birkbeck, and will combine a variety of structural, biochemical, biophysical and genetic methods to dissect and study the very large macromolecular complexes that mediate transcriptional activation. Alan's goal is to understand how these complexes act as focal points for transcriptional regulation.

Dr Iwan Evans

University of Sheffield

Studying integration of apoptotic cell clearance and macrophage migration dynamically in vivo

Iwan's research aims to understand how apoptotic cells influence macrophage behaviour and motility, both via intercellular signalling and events post-engulfment. To achieve this his lab is taking a genetic approach, studying a highly motile population of macrophages called hemocytes, which are found within fruit fly embryos. In identifying novel regulatory mechanisms, Iwan aims to provide new targets to manipulate macrophage behaviour in the wide range of human diseases in which they contribute to disease progression, such as cancer, atherosclerosis and chronic inflammation.

Dr Shukry Habib

King's College London

The molecular mechanism of Wnt-mediated asymmetric stem cell division

Shukry is a stem cell biochemist with research interests in understanding the extrinsic and intrinsic cues that choreograph stem cell behaviour during homeostasis, injury, and tumorigenesis. Recently Shukry has demonstrated that a localised source of Wnt signals induces oriented asymmetric cell division (ACD) of embryonic stem cells. By applying principles from bioengineering, stem cell biology and advanced imaging techniques, Shukry aims to gain insight into the underlying molecular mechanism of ACD at the single-cell level, as well as in a tissue context. These studies will aid in our ability to utilise and target critical cells for regenerative medicine.

Dr James Harker

Imperial College London

Contextual manipulation of the IL-6 family of cytokines to alter and enhance CD4+ T-cell immunity to respiratory viral infections

James is a viral immunologist with research interests in understanding the signals involved in generating potent antibody-mediated immunity to infections. His group in the Leukocyte Biology Section at Imperial College London will focus on determining the processes involved in promoting this type of immune response to respiratory viral infections, with the hope of developing novel therapeutic and vaccination strategies. The lab will use a number of in vivo infectious and genetic models that accurately reflect the complexities of the host immune response, allowing James to dissect how specific molecules, along with factors such as age, timing of infection and virus type, influence the outcome.

Dr Christopher Illingworth

University of Cambridge

Multi-locus models of pathogen evolution

Chris is interested in how genome sequences shed light on the rapid evolution of pathogens. A particular focus for his research is the development of tools for interpreting time-resolved data, where sequences collected across time show evolutionary changes in a population as they occur. Working in the Department of Genetics at the University of Cambridge, Chris hopes to better understand how pathogens respond to evolutionary pressures such as host immune responses and drug therapy.

Dr Zamin Iqbal

University of Oxford

Statistical methods for analysing complex genomic variation in human pathogens

Zamin studies the genomes of different strains of pathogens that cause human diseases. Unlike humans, whose DNA all looks remarkably similar, pathogen strains often have significantly different genomes, which they achieve by swapping large chunks of DNA. These differences are very important, as it is known that strains of a pathogen acquire new abilities (e.g. drug resistance in MRSA, immune evasion, or even the ability to infect humans) through these mutations. Zamin's lab aims to provide insight into pathogen biology and epidemiology, and directly assist clinical decisions, by producing computational tools that analyse new samples or outbreaks in the context of the 'super-genome' of the entire species.

Dr James Kirkbride

University College London

Psychosis risk over the life course: a multilevel, longitudinal investigation of social, economic and physical environmental risk factors at different stages in life

James is a psychiatric epidemiologist interested in understanding how exposure to social factors, including the environments in which we live, may contribute to our risk of psychosis over the life course. He is currently investigating how the social and environmental factors we are exposed to at different periods of our lives (in early infancy, childhood, adolescence and adulthood) may contribute to developing severe mental illnesses, such as psychotic disorder. He is particularly interested in social inequalities, minority position, and ethnicity. James tests his research questions in England, Sweden and Canada, applying multilevel and spatial regression techniques to longitudinal datasets available in these countries.

Dr Bon-Kyoung Koo

University of Cambridge

Characterisation of novel E3 ubiquitin ligases that are enriched in LGR5-positive intestinal stem cells and niche

Bon-Kyoung is a mouse geneticist with broad experience in the field of E3 ubiquitin ligases. He is based at the Cambridge Stem Cell Institute, where he studies the role of endosomal E3 ubiquitin ligases in two major signalling pathways. Currently, his research focus is on identifying and understanding the role of novel E3 ubiquitin ligases in homeostatic regulation of stem cells.

Dr Dante Mantini

University of Oxford

Large-scale alterations of cortical activity induced by brain lesions and their relevance to behavioural deficits

Dante is a cognitive neuroscientist who combines neuroimaging experiments and computational models to understand the functional architecture of the brain. He works in the field of brain connectivity, investigating how dynamic interactions between distant brain regions are generated. His current work focuses on examining changes in behaviour and brain connectivity following highly controlled lesions in the macaque brain. This research may have an impact on the way we view the effects of brain lesioning on cognition.

Dr Benedetto de Martino

University of Cambridge

Imperfect choice and the brain: uncertainty, value and decision making

Benedetto is a cognitive neuroscientist who works in the field of decision making. He combines economic models and the tools of cognitive neuroscience, with the aim of developing a realistic account of the behaviour underpinning complex phenomena in economics and finance. His focus is on studying how the human brain computes the values that guide decisions in the face of uncertainty and fragmented information. The goal is to clarify, at the neurobiological level, why some of the most important decisions we make in life are 'suboptimal' or 'imperfect'.

Dr Ainhoa Mielgo Iza

University of Liverpool

Studying the impact of a non-canonical CRAF-PLK1 signalling pathway in desmoplasia and pancreatic cancer progression

Ainhoa is a cancer cell biologist who works on understanding how tumour and stromal cells regulate vital processes, such as apoptosis, proliferation and migration, to survive and promote tumour progression. It has recently become evident that in carcinomas the non-malignant stromal cells play a key role in tumour progression and resistance to therapy. Thus, Ainhoa is currently focusing on understanding the molecular mechanisms regulating the proliferation and survival of cancer-associated fibroblasts (CAFs). A better understanding of how the proliferation of CAFs is regulated could help improve current anticancer therapies. Therefore, the overall goal of Ainhoa's research programme is to identify novel key regulators necessary for the aberrant proliferation of CAFs and to investigate the therapeutic benefits of inhibiting proliferation of CAFs in cancer.

Dr Gary Mirams

University of Oxford

Improving assessment of drug-induced cardiac risk with mathematical electrophysiology models

Gary is a computational biologist working on the prediction of potential cardiac side-effects associated with a novel drug compound during its development. Pharmaceutical companies can already perform experiments to measure how drug compounds affect some of the ion channel proteins that control the electrical wave that activates the heart. Gary is using mathematical models of cardiac electrophysiology to integrate this information by performing simulations of the electrical activity of the heart at the cell and tissue levels. The aim is to predict any increased risk of disturbances to human heart rhythm earlier in drug development and more accurately than the existing animal-based safety tests.

Dr Patricia Muller

University of Leicester

Mutant p53 enhances receptor recycling to enhance invasion and chemo-resistance

Patricia is a cancer biologist who has studied the role of mutant p53 proteins in cancer. She has characterised an important intracellular pathway (Rab-coupling protein-driven receptor recycling) as a molecular mechanism underlying mutant p53-driven invasion and metastasis. Mutant p53 expression frequently correlates with drug resistance, and preliminary data reveal a potential role for receptor recycling in mediating chemo-resistance. Using molecular and imaging approaches, Patricia will extend these studies to determine the molecular mechanisms underlying mutant p53-dependent chemo-resistance and to further characterise the molecular pathways regulated by mutant p53 to promote invasion and metastasis.

Dr Nathalie Rochefort

University of Edinburgh

Neuronal circuits and synaptic mechanisms of experience-dependent plasticity

Nathalie started her research group in 2013 at the Centre for Integrative Physiology at the University of Edinburgh. She is a sensory neuroscientist whose goal is to understand how neural activity in the visual cortex underlies our perception of a visual scene. By using the method of two-photon calcium imaging combined with electrophysiological recordings, the aim of her project is to determine how sensory experience durably modifies the activity of cortical neuronal networks.

Dr Helen Rowe

University College London

Epigenetic pathways through which endogenous retroviruses regulate cellular genes in pluripotent cells

Helen is investigating the function of the repetitive genome with a focus on endogenous retroviruses, which represent around 10 per cent of mammalian genomes. Her research, using the mouse model, has revealed that rather than being 'junk DNA', as previously thought, endogenous retroviruses recruit epigenetic marks and serve as important regulatory elements to affect gene expression, particularly in stem cells. This is because stem cells are enriched in novel factors that target retroviral sequences in order to protect genome integrity. By characterising these factors, Helen aims to uncover the mechanisms by which endogenous retroviruses regulate stem cell biology and early embryogenesis. This work is relevant to the understanding and development of stem cell therapies.

Dr Charlotte Stagg

University of Oxford

Exploring the role of inhibition in human motor plasticity

Charlie is a neuroscientist who is interested in understanding how the brain learns new motor skills. By combining advanced brain imaging techniques and non-invasive brain stimulation approaches, her group will explore the physiological changes underpinning human motor learning. In particular, Charlie is interested in exploring the role of GABA, the major inhibitor neurotransmitter, in motor plasticity. Ultimately this work should help inform new strategies to optimise learning, especially in the context of recovery of function after stroke.

Dr Daniel Streicker

University of Glasgow

Managing viral emergence at the interface of bats and livestock

Daniel is an infectious disease ecologist who aims to develop new strategies to mitigate the impacts of emerging infectious diseases. He seeks to achieve this by understanding the epidemiologial and evolutionary processes that underlie pathogen emergence and establishment in new host species. Based at the Institute of Biodiversity, Animal Health and Comparative Medicine at the University of Glasgow, he is currently investigating viral dynamics at the interface of vampire bats and livestock in Peru, by combining longitudinal surveillance, phylogenetics, metagenomics and field experiments. Statistical integration of these diverse datasets will empower data-driven epidemiological models, creating a platform to anticipate and control cross-species transmission.

Dr Thomas Walker

London School of Hygiene and Tropical Medicine

Wolbachia transinfection of Culex tritaeniorhynchus mosquitoes to impact transmission of Japanese encephalitis virus

Tom is based in the Department of Disease Control at the London School of Hygiene and Tropical Medicine and is working on developing a mosquito biocontrol method to reduce the transmission of Japanese encephalitis virus (JEV) using the endosymbiotic bacterium Wolbachia. His research aims to determine whether particular strains of this bacterium can prevent or reduce the transmission of JEV in mosquitoes. Laboratory-based experiments to infect mosquitoes with Wolbachia and to determine the subsequent effects will aim to form the basis for an applied control programme to reduce JEV transmission in wild mosquito populations.

Dr Simone Weyand

University of Cambridge

Towards a molecular understanding of neurotransmitter transporter cellular activities

Simone is a biochemist and biophysicist who has worked on the structure determination of membrane proteins, such as the bacterial transporter Mhp1 and the human histamine H1 receptor, by the use of X-ray crystallography. Her Fellowship work uses a holistic approach to understanding the molecular mechanism of human neurotransmitter transporters by investigating the high-resolution structure and the functional analysis and trafficking in the cell. This combined approach, including different techniques, will provide deeper insights into the basic principle of action of these proteins and will eventually enable a more rational and efficient drug design.

Dr Daniel Wilson

University of Oxford

Statistical methods for whole-genome phenotype mapping in bacterial populations

Daniel is an evolutionary geneticist at the University of Oxford, where his laboratory investigates pathogen evolution and epidemiology via whole-genome sequencing. He is a collaborator in the Modernising Medical Microbiology Consortium, whose aim is to harness genomics for microbiological diagnostics and infection control in hospitals. Daniel's work currently focuses on the identification of genetic variants in pathogen genomes that explain differences in the frequency and severity of infections, particularly hospital-associated infections including Staphylococcus aureus, Clostridium difficile and norovirus.

Dr Duncan Wilson

University of Aberdeen

Overcoming nutritional immunity: micronutrient acquisition mechanisms of pathogenic fungi

Duncan is a medical mycologist interested in the struggle for essential micronutrients between human pathogenic fungi and their hosts. Certain trace minerals, such as iron and zinc, are actively withheld from pathogens in a process called nutritional immunity. Therefore, pathogenic microbes must have evolved specialised uptake systems in order to proliferate in their hosts and cause disease. Duncan is using a combination of molecular and cellular biology, together with models of host-pathogen interactions, to dissect the mechanisms of micronutrient assimilation by the major human fungal pathogen, Candida albicans. His aim is to understand how this process contributes to pathogenesis and disease.

Dr Andrew Wood

University of Edinburgh

Chromosomal instability during normal and condensin II-deficient haematopoiesis

Andrew's laboratory studies the mechanisms that maintain a correct number of chromosomes during cell division. He uses blood cell development to understand how effectively these mechanisms operate in vivo, and the consequences of their malfunction on cellular proliferation, differentiation and malignancy.

2012

Dr Bungo Akiyoshi

University of Oxford

Elucidating the mechanism of chromosome segregation in Trypanosoma brucei

From September 2013, Bungo will be working in the Department of Biochemistry, University of Oxford, studying trypanosomal kinetochores as a group leader.

Dr Stephen Baker

University of Oxford

The epidemiology, genomics and longitudinal immune response of Shigella infections in Vietnamese children

Stephen is a molecular microbiologist based at the Wellcome Trust Major Overseas Programme in Ho Chi Minh City, Vietnam. He has been there since November 2007 and is the head of the enteric infections research group, which studies the microbiology, genetics, epidemiology and treatment of enteric infections in low-income countries. Focal pathogens include Norovirus, Shigella spp. and Salmonella typhi, the causative agents of diarrhoea, dysentery and typhoid fever, respectively. His current direction combines microbiological, immunological and geographical information to study how organisms are transmitted in urban environments and how this interplay can be used to design and implement vaccination strategies.

Dr Jennifer Bizley

University College London

Listening in a noisy world: the role of visual activity in auditory cortex for sound perception

Jennifer is a sensory neuroscientist whose goal is to understand how neural activity in auditory cortex underpins our perception of a sound scene. By combining electrophysiological and behavioural approaches Jennifer aims to explore how the activity of single neurons and neural populations results in sensory discrimination. Jennifer's current research explores how and when visual information influences auditory perception, and how visual signals alter activity in auditory cortex.

Dr Maciej Boni

University of Oxford

Epidemiology of human influenza in Vietnam

Maciej is currently running a serial seroepidemiology study on human influenza in southern Vietnam and an influenza-like illness study in Ho Chi Minh City. The results of this work will be used to determine whether influenza viruses persist year-to-year in Vietnam and, more broadly, to determine whether countries like Vietnam have the right conditions to seed influenza epidemics in other parts of the world.

Dr Tiago Branco

MRC Laboratory of Molecular Biology

Dendritic integration in the ventromedial nucleus of the hypothalamus

In 2012 Tiago started his own group at the MRC Laboratory of Molecular Biology, where he combines physiological and molecular methods to investigate how the mouse brain implements the computations that underlie innate behaviours. He is currently a Visiting Scientist at the Janelia Farm Research Campus, working on synaptic integration in the hypothalamic circuits that control feeding behaviour.

Dr Edgar Deu

The Francis Crick Institute

Functional characterisation of essential enzymes in Plasmodium

Edgar's research focuses on identifying and studying the biological function of novel antimalarial targets, with the aim of opening new therapeutic avenues to fight malaria. He combines chemical biology approaches with genetic methods to identify enzymes that are essential for parasite development, validate them as antimalarial targets and characterise their molecular functions. So far his research has particularly focused on the biological roles of a multifunctional protease involved in red blood cell invasion, parasite maturation, and parasite egress from infected erythrocytes.

Dr Omer Dushek

University of Oxford

Predicting efficient T-cell activation with therapeutic applications

Omer is currently working at the Sir William Dunn School of Pathology at the University of Oxford. His research in molecular immunology aims to use a combination of mathematical modelling and quantitative experiments to understand the complex interplay between the signalling proteins that regulate the activation of T lymphocytes.

Dr Yi Feng

University of Edinburgh

Live imaging and genetic analysis of the inflammatory response upon oncogene-induced tissue homeostasis disruption and its contribution to tumour initiation in zebrafish larvae

Yi’s lab at the MRC Centre for Inflammation Research at the University of Edinburgh uses a combination of live imaging and genetic analysis in zebrafish to study the earliest events of tumour initiation in vivo. Her research focuses on interactions between normal host tissue with transformed cells and infiltrating innate immune cells, and she has demonstrated that the latter mount a trophic response toward emergent transformed cells. Her research aims to understand underlying cellular and molecular mechanisms regulating this trophic inflammation response during tumour initiation.

Dr Stephen Graham

University of Cambridge

Molecular mechanisms of membrane trafficking in pathology and infectious disease

Stephen is interested in how eukaryotic cells effect communication between their membrane-bound compartments, how such communication is regulated, and how viruses subvert these mechanisms to their own ends during infection. He uses primarily biophysical and structural biology techniques to address these questions and is currently based in the Virology Division of the Department of Pathology, University of Cambridge.

Dr Garrett Hellenthal

University College London

Inferring human colonisation history using genetic data

Garrett has been working at University College London since 2012, developing statistical methods to infer population history using DNA. He is currently developing methods to identify periods in the past when worldwide populations have exchanged DNA, for example due to invasions or migrations, and to describe the genetic make-up of the groups involved in these events. One current project involves characterising the genetic structure of the United Kingdom as part of the People of the British Isles project.

Dr John James

University of Cambridge

Decision making in immune cell activation

Our immune system is a network of white blood cells and proteins that keeps us healthy. John's research focuses on how T cells in the immune system make a committed decision to initiate an immune response on encountering an infected cell. The signalling network inside these cells is complex, so John has reconstituted a 'model' T cell that provides a more tractable way to explore the molecular mechanism of the decision-making process. This research will lead to a better understanding of how our immune system can discriminate between infected and healthy cells, and how we may be able to manipulate it therapeutically when needed.

Dr Jens Januschke

University of Dundee

Recycling polarity – mechanisms controlling stem cell polarity in consecutive divisions in the developing Drosophila central nervous system

Central to Jens's research interests are the mechanisms behind the dynamics of cell polarisation in cycling cells. In particular, he is using life-cell imaging approaches to study how cell polarity and asymmetric division are linked in neuroblasts, the rapidly dividing stem cells of the developing Drosophila central nervous system.

Dr Pablo Lamata

King's College London

Diastolic-PM: diastolic biomarkers based on physiological models

Pablo is investigating the diastolic performance of the heart. He is developing new methods to measure the heart's speed of relaxation, the compliance of the muscle, and the pressure driving the blood flow during the filling phase of the heart cycle. The methods are based on the combination of recent advances in magnetic resonance imaging and computational cardiac modelling.

Dr Selinda J Orr

Cardiff University

Collaborative and redundant roles of CLRs in antifungal immunity

Selinda's laboratory is part of the Myeloid Cell Biology Group at Cardiff University. She aims to understand collaborative responses between C-type lectin-like receptors and to determine how these responses could be targeted to improve antifungal immunity.

Dr Christopher Rodgers

University of Oxford

Advanced human cardiovascular magnetic resonance spectroscopy

Chris runs the Cardiac Spectroscopy group at the Oxford Centre for Clinical Magnetic Resonance Research, Department of Cardiovascular Medicine, University of Oxford. His research group develops methods for magnetic resonance imaging and spectroscopy of the human heart at ultra-high field strength (7 Tesla). His group has recently recorded the first cardiac 31P magnetic resonance spectra at 7T, already showing significantly better quality than established field strengths.

Dr Tim P Vogels

University of Oxford

Controlling balanced cortical dynamics on slow and fast timescales

Tim is working to understand and reproduce how the brain processes sensory information, by investigating the rules by which its neuronal architecture is constructed and maintained. He is exploring the tight interaction between neuronal activity and the network structure that sustains this activity and the manifold rules that govern these interactions, differing by cell type. Due to the complexity of such high-dimensional systems, Tim simulates these interactions in abstract, simplified computer models. He aims to test out ideas of what such rules could be, and to make experimentally testable predictions about them. This in turn will help to further flesh out a more exact model of the brain, and hopefully spawn further questions and ideas to try out.

Dr Kevin Waldron

Newcastle University

Mechanisms of copper and silver toxicity in Staphylococcus aureus

Based at Newcastle University, Kevin's research aims to understand the roles of metal ions and metalloproteins in biological systems, how metal selectivity is achieved in vivo, and how metals cause toxicity when metal homeostasis breaks down due to metal excess, genetic mutation or disease. This puts his research interests on the interface between inorganic chemistry and biochemistry. His Fellowship project aims to bring together data obtained by a range of biochemical, genetic, biophysical and proteomic approaches to understand the molecular mechanisms by which copper ions kill Staphylococcus aureus cells, and to assess the risk of spontaneous resistance arising.

Dr Sarah Woolner

University of Manchester

Mitotic spindle orientation and the mechanical tissue environment

Sarah's research aims to understand how cell behaviour in developing embryos is influenced by the external tissue environment. In particular, she is focusing on determining how cell division orientation is directed by mechanical tissue cues. The orientation of cell division plays a vital role in shaping and organising tissues and in determining cell fate.Sarah's lab is based in the Wellcome Trust Centre for Cell-Matrix Research at the University of Manchester.

People we've funded

Many of our grantholders carry out research in Africa and Asia. See our directories: