Senior Research Fellowships in Basic Biomedical Science: people we've funded

This list includes current and past grantholders.

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2017

Professor Fred Antson

University of York

Structure and mechanism of nucleic acid-processing machines in viral biogenesis

Viruses are the most common biological entities on our planet, infecting all living things. In humans, viral infections like glandular fever, dengue fever, Ebola and influenza cause illnesses and deaths worldwide, particularly in the very old or young or people with lowered immune defences. Some viruses can cause life-long infections as they are impossible to eradicate using current treatments. This can lead to heart problems or cancer. Others, such as Zika, can cause serious developmental damage to unborn babies. Viruses can only replicate in cells and they use dedicated capsules to protect their genes while passing to another host. During infection, new copies of the virus’s genes are made and loaded into capsules to make new virus particles that burst out of the host and spread to other cells. The virus employs highly specialised machines to copy its genes and to load them into the capsules.

We will use cryo-electron microscopy, X-ray crystallography and approaches that sense single molecules, to examine the machines and watch them work. The research will provide detailed information about what the machines look like and how they function.

Our findings  will inform the development of new treatments that can prevent or reduce viral infections.

Dr Alexandra Brand

University of Aberdeen

Navigation and steering systems in fungal pathogens – the route to fatal infection

Invasive candidiasis is a fungal disease caused by Candida albicans and affects about 250,000 hospitalised patients a year. Candidiasis can be fatal if the fungus colonises internal organs such as the lung, liver, spleen, kidneys and bone.

This research aims to understand how microscopic fungal filaments can penetrate human body tissue so effectively. We know they use an internal steering mechanism to navigate through their environment which is essential for tissue penetration. Our research goals are to find out how the steering mechanism works and how the fungus responds to the internal environment of the human body. We cannot study the fungus inside humans so we will use cells and biomaterials that mimic the tissues the fungus encounters during infection. We will also find out whether cells of the immune system respond differently to the fungus in these surroundings and we will find out whether the steering defects we have discovered affect the ability of the fungus to invade living tissue and activate immune cells using the transparent larvae of zebrafish.

This research will give us important insights as to how the fungus behaves in living tissue and how it disseminates to diverse internal organs during infection.

Dr Jeremy Carlton

King's College London

Membrane remodelling during mitotic exit

Cell division is the process by which a single cell divides into two daughter cells. It is essential for life, being necessary for the growth, development and repair of all tissues in the body. Errors in cell division can lead to diseases such as cancer, however, despite being so important, there are still many things about this process that we don’t understand. As well as containing DNA, cells also contain a number of internal compartments called organelles that help them live. Some of these organelles fragment when cell division begins and this allows DNA separation to occur. As cells finish dividing, organelles must be divided equally into daughter cells, and organelles that were fragmented must be reassembled.

I want to discover how an organelle that encloses the nucleus (and fragments when cells begin division) is reformed when division ends. I also want to find out how a large organelle called the endoplasmic reticulum – which  fills most of the cell’s interior – is separated during division and how a group of membrane-binding proteins called endosomal sorting complexes required for transport (ESCRTs) assemble into a machinery that shapes, separates and reforms organelles during cell division.

Our findings will help us discover more about how cells work and reveal more about the cellular processes that guard against the development of cancer.

Professor Simon Davis

University of Oxford

Decision-making by lymphocytes

Our immune systems respond to viruses and other harmful threats by triggering the replication of those white blood cells that are best-suited to neutralising each specific threat. Remarkably, however, no-one properly understands how each white blood cell decides to respond, despite the importance of the mechanism.

For many years, we have studied the behaviour and functions of proteins present on the surfaces of white blood cells and it has been proposed that changes in their organisation are a key part of how immune responses start. Developments in microscopy mean that we can now finally see whether the proposed re-organisation takes place at the start of immune responses, allowing us to directly test this theory.

Having determined how they start, we will be much better placed to boost helpful immune responses against diseases such as cancer and block harmful ones that cause diseases such as diabetes.

Dr Omer Dushek

University of Oxford

Control of T-cell responses by accessory receptors revealed by phenotypic models

T cells are important immune cells responsible for fighting infections and cancers. They continuously scan other cells for these threats using a receptor on their surface. Basic research has shown that, besides the main receptor, other ‘accessory’ receptors also control how T cells respond but it is not known how this happens. There has been a focus on identifying the molecular parts that process information from receptors which could improve T cell therapies for cancer treatments. This has revealed enormous complexity but has not greatly improved our understanding of how T cells are controlled.

Instead of studying the detailed parts, we will study how triggering accessory receptors changes the T cell response. This will lead to a more precise understanding of how all receptors work together to control T cells.

We will use our findings to benefit human health.

Professor Ian Goodfellow

University of Cambridge

Entry, innate sensing and replication of enteropathogenic caliciviruses

Noroviruses and sapoviruses have a huge impact on society and cost more than $60 billion every year, yet we have no drugs or vaccines to prevent or treat infections. Noroviruses were first identified in 1972 but we have only been able to grow them in the lab since late 2016. We are now able to address some fundamental questions on how they infect cells and cause disease. We have discovered that a set of molecules on the surface of cells known as lectins, in combination with blood group antigens, potentially play a role in determining host susceptibility to infection.

We will further characterise this interaction and identify the role these molecules play in the viral life cycle. We also wish to understand how cells respond to infection as we have previously shown that regulating this response using clinically approved drugs can inhibit viral replication. We also aim to identify cellular proteins required for viral replication as new potential targets.

This work will give us new information relating to biological processes in host cells and how cells respond to infection. The long-term focus of our work is to develop ways of preventing and controlling gastroenteritis caused by noroviruses and sapoviruses.

Dr Katie Hampson

University of Glasgow

The science of rabies elimination

Rabies is a horrific but preventable disease that kills thousands of people every year in low-income countries. International agencies now advocate investment in rabies control and have set a 2030 target for global elimination. The major research questions are now how to ensure the effective rollout and implementation of control programmes and address challenges during the endgame when incidence has been reduced to low levels and may circulate undetected.

I will address these questions through synergistic research embedded in rabies control programmes around the world. I will pilot approaches for the surveillance of rabies to increase case detection, improve treatment of people bitten by rabid animals and track the spread of infection in real-time. Capitalising on large-scale dog vaccination programmes will enable me to address questions about how long it takes to control rabies and what impedes progress towards elimination. My aim is to build an operational toolbox underpinned by a fundamental understanding of rabies dynamics to guide policy and practice.

Working with policy-makers and practitioners to integrate my research into ongoing rabies control programmes will bring immediate benefits to their implementation and success, and transferrable insights to guide elimination efforts and policy around the world.

Dr Ian Humphreys

Cardiff University

The role of innate immune regulation in viral pathogenesis and the development of anti-viral T cell memory

Our body’s immune system protects us from infection, but sometimes it overreacts and causes organ damage. A protein called interferon-induced transmembrane protein 3 (IFITM3) limits severe viral diseases. IFITM3 is known to stop some viruses dividing but I discovered that it also suppresses overactive immune responses, known generally as inflammation that is triggered by viruses.

I will study cytomegalovirus, a virus that causes disease in people with a suppressed immune system and young children. My study will find out how IFITM3 limits inflammation and I will examine whether targeting these pathways can help treat clinical problems caused by virus-induced inflammation. Vaccinations work by triggering immunological memory that can remember, respond to and control infections. Cytomegalovirus promotes long-lasting strong immunological memory. Studying how this virus triggers memory could help with the design of vaccinations – and a safe version of cytomegalovirus could be used as a vaccine. I will identify early events required for cytomegalovirus-triggered immunological memory formation and identify whether factors that dampen these responses can be targeted to enhance immune protection afforded by safe cytomegalovirus-based vaccines.

My findings will uncover how early inflammatory events can be inhibited to treat clinical problems caused by virus-induced inflammation and be enhanced to improve vaccine-induced immune protection.

Dr Grzegorz Kudla

University of Edinburgh

Next-generation RNA genotype-phenotype mapping

The first human genome sequence was published in 2000 and thousands of genomes have been analysed since that time. We need to be able to predict the effects of mutations on molecules to fully use the information contained in these genomes, cells and organisms. To make these predictions, we first need to measure the effects of many mutations on each outcome.

We will develop methods that can be used to study the effects of thousands of mutations in parallel. We will apply these methods to study the mutations in a model yeast gene and try to understand how the different effects of mutations are related to each other – for example, whether we can predict the effects of mutations on yeast growth from their effects on molecular interactions of the model gene. We will then study a class of mutations that were long thought to have no effect in humans – the so-called ‘synonymous mutations’.

We have already shown that synonymous mutations influence gene expression and we will use our data to uncover the mechanisms underlying these effects.

Dr Serge Mostowy

Imperial College London

Use of the cytoskeleton to control Shigella infection

The intracellular bacterium Shigella flexneri is a model pathogen that can be used to address key issues in biology, including how bacteria can move inside host cells or be recognised by the immune system. Host cells employ septins, a poorly understood component of the cytoskeleton, to restrict the motility of Shigella and target them for destruction by autophagy, an important mechanism of the innate immune defence. We recently established the antibacterial activity of septin caging and discovered a fundamental link between mitochondria and the assembly of septin cages around Shigella. It is important to now fully decipher the underlying molecular and cellular mechanisms and to validate these events in vivo using relevant animal models. I developed zebrafish infection models to study the cell biology of Shigella infection in vivo and to discover new roles for septins in host defence against bacterial infection. This approach has enabled in vivo studies of single cells and the whole animal.

My findings will provide fundamental advances in understanding cellular immunity. This should provide vital clues towards understanding bacterial disease and for illuminating new therapeutic strategies.

Professor Stuart Neil

King's College London

Evasion of innate immunity by HIV-1 during the early stages of viral replication

HIV-1 must avoid innate immunity in humans so that it can achieve successful transmission from one person to another.

We want to understand two aspects of these immune evasion strategies: how HIV-1 avoids a family of membrane proteins, known as IFITMs that block the entry of the virus into its target cell; and how it disables the early warning systems that detect invading viruses once inside. We have found that isolates of HIV-1 that represent those transmitted between people are inherently resistant to the activities IFITM proteins and this is a major contributor to their overall avoidance of innate immunity. We propose to understand how the transmitted viruses achieve IFITM-mediated inhibition. We will determine how IFITMs affect the entry process of the virus itself, the cell types it can replicate in and how antibody responses that arise in the first few months after infection lead to IFITM sensitivity. We will also study the role of a small viral protein, Vpr, that is associated with the HIV-1 particle. Our preliminary evidence indicates that Vpr shuts down the cell’s ability to detect virus infection and we will determine the mechanism by which it does so.

Studying these mechanisms will potentially yield new therapeutics to treat HIV and AIDS.

Dr Gisela Orozco

University of Manchester

Identification of rheumatoid arthritis causal genes using functional genomics

Rheumatoid arthritis (RA) is a chronic disease that causes inflammation and pain in the joints. There is currently no cure and treatments are sometimes not effective. Genetic studies have identified changes in the DNA sequence that increase the likelihood of developing RA but so far it is not known how the DNA changes increase the risk of RA. The aim of this project is to identify which genes the RA variants affect and to understand how changes in the DNA sequence between genes cause RA. It is thought that the DNA changes control the activity of genes but the genes being controlled may lie some distance away. However, DNA is folded so that the changes that predispose to RA and the genes they regulate are brought together. These folds are different in different types of cells.

I will investigate how the DNA folds and the changes in DNA alter the way genes are regulated in cells from patients with RA.

My findings will provide information on the cause of the disease and will suggest new options to treat RA, providing better patient care and improved outcomes.

Dr Richard Poole

University College London

Sexy glia: developmental plasticity during glia-derived neurogenesis

Animals are composed of many different types of cell, each with their own function. In certain circumstances, cells with one function can switch to become cells with a different function. For example, adult newts can regenerate their limbs and this requires nearby cells to switch function and produce the cell types that make up a limb. These cell-type switches can also be observed in our brains. In a few tiny regions of the adult brain, new neurons can be generated from glial cells, the other main cell type in the brain, during learning or in response to brain trauma. Harnessing this cell plasticity has enormous therapeutic potential.

We want to understand how glia-to-neuron switches occur. Conservation of biological processes allows us to study these phenomena in the nematode worm C. elegans, a simple genetic model system.

Mechanistic insights into these cell-function switches in the nervous system may, in the future, allow us to regenerate large regions of the brain or to produce neurons in the laboratory to replace those that are lost in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

Dr Rebeccah Slater

University of Oxford

Understanding mechanisms that drive pain perception in early human development

Pain in infancy has negative long-term consequences and its prevention is a clinical priority, but adequate pain treatment requires mechanistic understanding of the structural and functional development of human pain-related brain circuitry. Recent scientific and technological advances provide insights into how noxious information is transmitted to the infant brain, providing a platform to ask how intrinsic brain network connectivity and the environment affect pain-related brain activity, behaviour and ultimately pain perception in the developing infant nervous system.

As infants cannot describe their pain, we are reliant on alternative methods to measure their pain experience. Our goal is to understand the mechanisms that drive and modulate pain perception in early human development. We will ask how inherent differences in how the brain behaves at rest influences pain-related brain activity, and how this relationship is altered by environmental factors and pathology. We aim to establish how the development of structural and functional network connectivity alters pain experience, and influences the dynamic relationship between brain activity and behaviour.

Our findings will help us develop new pain treatment options for infants.

Dr Julie Welburn

University of Edinburgh

Molecular basis for motor-cargo cooperation in mitosis

It is essential that all living organisms transmit their genetic information accurately from one generation to the next. When a cell divides, it distributes the previously duplicated chromosomes to each daughter cell so that they inherit the same genetic message. Defects that result from unequal chromosome segregation can lead to dramatic consequences. Aneuploidy is frequently observed in cancer and results in genetic diseases such as trisomies including Down’s syndrome. The cell uses microtubules – long dynamic filaments that store energy – to segregate its chromosomes equally. Multiple nanoscale molecular motors organise the microtubules so that they can assemble to form the chromosome segregation machinery called the spindle.

We want to understand how these motors coordinate their activities to shape microtubules into a spindle and then attach and move chromosomes along it. We will define how motors achieve movement and transport at the molecular level and how cancer or cell death can occur when the process fails.

This research is key to understanding the molecular processes of cell division in the eukaryotic kingdom and will create opportunities for the discovery of anti-cancer drugs that target these motors.

Professor Magdalena Zernicka-Goetz

University of Cambridge

Embryo architecture, potency and tissue interactions during mouse and human development

The first weeks of embryo development from a fertilised zygote is a critical period when many pregnancies fail. We aim to relate how changes in embryo architecture go hand in hand with new genetic instructions that give the early embryo its correct anatomy.

We will begin our studies when the embryo comprises only eight cells and first changes its shape, which is important for different cell types to emerge. The embryo next changes its architecture when it implants into the womb and becomes inaccessible. We have developed technology for culturing mouse and human embryos in a dish throughout and beyond implantation (under approved conditions). This will allow us to uncover mechanisms underlying self-organisational properties of the mammalian embryo. We have also established conditions in which stem cells in a dish develop into structures that strongly resemble natural embryos.

We will study previously hidden stages of development to understand how the different cell types interact to shape the body plan. These interactions are prerequisites for a successful pregnancy and we will use our findings to provide insight into the causes of early pregnancy loss.

2016

Dr Hashim Ahmed

University College London

Transforming the screening, diagnosis and treatment of prostate cancer

At the moment prostate cancer is diagnosed using a rectal examination and a biopsy test that are not accurate. My previous research has shown that using MRI scans and MRI-guided biopsies can more accurately find out how aggressive a cancer is, so my work will involve redefining risk using these accurate tests.

Screening for prostate cancer is not recommended in the UK. I will test whether MRI might be used as a screening test in high-risk men. Advanced prostate cancer is treated with medication alone. I want to test whether heat-based treatments can be used to successfully treat the main prostate tumour. Randomised controlled trials in surgery are difficult. This is a bad thing for future patients because improvements in treatments may not get to clinic. I will try a new way of running randomised surgical trials.

This study’s findings will hopefully improve the screening, diagnosis and treatment of prostate cancer.

Dr Arockia Jeyaprakash Arulanandam

University of Edinburgh

Molecular mechanisms of centromere inheritance and kinetochore function

The integrity of life relies on the ability of cells to faithfully pass on their genetic information in the form of chromosomes to daughter cells when they divide. Aberrant chromosome distribution leads to daughter cells with an abnormal chromosomal number, a state called aneuploidy. Aneuploidy is often implicated in cancer and causes infertility, miscarriages and birth defects such as Down's syndrome. The key protein machinery that facilitates chromosome distribution to daughter cells is called the kinetochore, which is assembled on a specialised chromosomal site called the centromere. Kinetochores physically attach chromosomes to filamentous structures called microtubules to achieve chromosome separation. A large number of different proteins regulate these biological processes.

We aim to understand how protein machineries establish and maintain centromere marks on chromosomes and how kinetochores assembled on them help in distributing chromosomes equally and identically to daughter cells. We will do this by determining and analysing structures of centromere-associated molecular machines as they interact with their binding-partners.

Understanding the mechanisms that ensure accurate chromosome separation is crucial in fighting several important disorders.

Dr Jonathan Chubb

University College London

Single cell decision making in development and dedifferentiation

The decisions that single cells make are central to many processes that occur during the development of an embryo. Single cell decisions are also a necessary feature of generating stem cells in the laboratory. Cell decisions are determined by the activity of specific genes in individual cells. However, the normal methods that are used to measure gene behaviour lack the necessary detail to measure gene activity in single cells. These methods have, until recently, only been able to measure the gene behaviour from many thousands of cells, which hides the gene activity that is required for single cell decisions. We have developed methods to directly view gene behaviour in single cells, so now it is possible to understand precisely how these genes contribute to cell decisions.

Stem cells show great potential for regenerative medicine, where they could assist in the repair of bodily structures and functions after injury or illness.

Dr Atlanta Cook

University of Edinburgh

Towards a mechanistic understanding of RNA processing machines

Sleeping sickness, Chagas disease and leishmaniasis are common in tropical and subtropical areas. These diseases are deadly but they are largely ignored by pharmaceutical companies. They are caused by a family of single-celled parasites called kinetoplastids. In all living organisms, genetic instructions for making proteins require messenger RNAs (mRNAs), which are short-lived copies of DNA. Unlike their human hosts, kinetoplastids produce some of their mRNAs in an incomplete, encrypted form. They need to be edited or re-written in a specific way to allow production of the proteins that are essential to the parasite’s survival. A remarkable and unique molecular ‘machine’ containing 14–15 different protein molecules is responsible for the RNA editing process. This is not found in humans and is essential for parasite survival, so it is an attractive target for drug development. However, we have limited information about this machinery works.

We will capture snapshots of individual parts of the machine during the editing process and examine their structures to understand how they work.

Our findings could highlight potential new directions for drug development for these diseases.

Professor Anna Gloyn

University of Oxford

Defining mechanisms for pancreatic beta-cell dysfunction in type 2 diabetes

Type 2 diabetes is a leading cause of illness and death across the world and current strategies for prevention and treatment are inadequate.

I will identify fundamental processes involved in the development of type 2 diabetes by using human genetics and the molecular characterisation of the pancreatic islet to generate novel insights into disease biology.

My findings will provide the basis for more effective preventive and therapeutic approaches that can reduce the burden of disease.

Professor Alexander Gourine

University College London

Homeostatic monitoring and control of regional brain blood flow

The brain has a very high metabolic rate because of the activities of millions of nerve cells that process information. The brain subsequently requires constant and optimal nutrient and oxygen supply, as well as the effective elimination of carbon dioxide and this is ensured by elaborate physiological mechanisms that control cerebral blood flow. Sustained efficacy of these mechanisms maintains neurological health and promotes brain longevity. Dysfunction may result in damage to nerve cells, contributing to cognitive impairment and neurodegenerative disease.

I will study the molecular and cellular mechanisms underlying the effects of carbon dioxide and oxygen on the flow of blood in the brain. I will also examine the mechanisms responsible for increases in local brain blood flow which accompany heightened nerve cell activity.

This research is expected to contribute to our understanding of how brain blood flow supports dynamic changes in local neuronal circuit activity and how brain blood flow is controlled to maintain a consistent environment and protect neuronal networks from deleterious changes in carbon dioxide concentration and oxygen availability.

Dr Matt Jones

University of Bristol

Decoding neural assemblies over multiple brain regions, extended experience and sleep-wake cycles

UK cashpoints return your card before dispensing money. US cashpoints give out money before returning your card. Knowing how to use a UK cashpoint helps you understand how to use a US ATM but how do our brains cope with these differences and why do they sometimes fail to cope? These questions can be answered by mapping brain activity patterns during one experience then seeing how those patterns support future learning and adapt to store new knowledge. In order to measure the activity of lots of individual brain cells, we will use rats with tiny wires implanted in their brains. Rats like using cashpoints and they will happily press or poke things to trigger rewards. Like us, rats tend to perform better after a nap, probably because brain cells activated during learning are then reactivated during sleep. This unconscious mental replay helps file new knowledge so it can be used to help make the right choice next time. These experiments will tell us how brains adapt to their surroundings to let our past shape our future. It will also show why sleep is so important and how poor choices might be corrected.

Dr Nicholas Lesica

University College London

Neural circuits for selective auditory filtering

We will study the brain circuitry that underlies our ability to understand speech in a noisy environment by investigating how the cortex and the thalamus work together to enhance brain activity related to sounds.

We will use animals in our experiments to measure brain activity at a level of detail that is not possible in humans, and we will use new techniques allowing us to directly manipulate the activity of specific brain cells using light. By examining brain activity while animals are performing an auditory task, we can determine how that activity changes when attention is focused on different sounds. We can then determine how these changes depend on the activity of different types of brain cells by using light to activate or suppress activity in these cells during the task.

Our findings will help us understand our ability to understand speech in noisy environments and allow us to suggest directions for the development of therapies to improve speech understanding in people with hearing impairment.

Professor Karla Miller

University of Oxford

Linking MRI and microscopy for multi-scale neuroscience: mechanisms, diagnostics and anatomy

Magnetic resonance imaging (MRI) measures water, which exists in virtually every tissue in the body, including the brain. Although MRI images have 1 mm pixels, they have the potential to reveal information about tissue on the order of a micrometer which is 1,000 times smaller. This is because water is very sensitive to microscopic spaces and biological molecules. This enables MRI to detect subtle changes in brain disease happening at the microscopic scale. While these methods have exquisite sensitivity, they lack specificity; a given change measured with MRI could come from several plausible changes to brain tissue.

This research aims to improve our ability to interpret MRI by improving our understanding of how underlying microscopic properties of tissues alter the MRI signal. We will develop methods to link MRI at millimeter resolution to direct measurements using microscopes. By scanning brains after death, we can directly compare MRI and microscopy data in the same tissue to reveal their relationship. We will use these techniques to study brain anatomy at a very fine scale, to provide MRI microscopy markers in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and study how the brain rewires itself to learn new skills.

Dr Kevin Murphy

Assessing the health of ageing blood vessels in the brain using fMRI

Problems with the brain caused by poor blood flow are on the rise due to our ageing population. Disorders such as stroke and haemorrhage affect 272,000 people in the UK annually, costing the NHS £3.2 billion. There is evidence to suggest that poor blood flow is a factor in conditions associated with memory problems, such as dementia and Alzheimer’s.

I plan to develop a way of assessing the health of the brain’s blood vessels. This will allow researchers to track deterioration of the vessels as people age and will open the possibility of treating associated brain conditions before they become problematic. Functional magnetic resonance imaging (fMRI) is an ideal method to do this because the signals it measures are derived from the properties of the brain’s blood vessels. Smooth muscles around small arteries in the brain allow them to open to increase blood flow when more blood is required in a particular area of the brain. If the muscles are not functioning well, too little blood will be supplied, causing problems for the brain.

I will develop a way to measure how well the smooth muscle responds to the brain’s needs and use this tool to demonstrate how this blood vessel function changes with age and disease.

Dr Heath Murray

Newcastle University

Investigating the physiological DNA replication initiation reaction

Genome duplication is required for cell proliferation in all organisms. This essential process involves the concerted activity of several multiprotein complexes to replicate an exact copy of the DNA. The bacterial DNA replication machinery is significantly simpler than the related eukaryotic system, making it well suited for detailed analysis. Additionally, the bacterial DNA replication machinery is an attractive drug target, and new antibiotics are urgently needed to combat drug-resistant strains. In all cells, chromosome replication requires key initiator proteins to unwind the DNA at specific sites called origins. Despite the fundamental importance of DNA replication initiation, crucial aspects of the process remain poorly understood.

I have developed new tools that allow the normally essential DNA replication initiation factors to be either removed or mutated. This opens the possibility of determining all of the sites in both the chromosome origin and the proteins required for the initiation of DNA replication.

My long-term goal is to expand this toolkit and investigate the entire DNA replication machinery.

Dr Eugenia Piddini

University of Bristol

Understanding the mechanisms of cell competition and its role in tissue biology

The health of an organism relies on the health of its constituent cells. To help maintain a healthy tissue composition, a process of competition between cells has developed. It selects the best cells in tissues based on their survival characteristics, or ‘fitness’. When cells of differing fitness levels come into contact, weaker cells, which would be perfectly viable on their own, become the losers and are eliminated by fitter cells through induction of cell death.

In this project we will combine work using the fruit fly as a model organism with work using mammalian cultured cells to significantly deepen our knowledge of how cells compete in tissues. We will identify and validate new molecules that control cell competition, identify key health and disease contexts where cell competition plays a role. We will also investigate how cell competition could be exploited therapeutically to replenish unhealthy tissues with healthy cells.

Cell competition will affect numerous aspects of tissue biology, possibly acting as a quality control mechanism to eliminate unfit or harmful cells as they arise. Correspondingly, if properly harnessed, cell competition could open the door to novel therapeutic strategies, for example by improving the efficiency of stem cell therapies.

Dr Elena Seiradake

University of Oxford

Adhesion GPCRs in the neural and vascular systems: from complex structures to cellular functions

A family of proteins known as the adhesion G-protein-coupled receptors (adhesion GPCRs) are produced by cells in the brain and blood vessels. They have been implicated in a number of severe human disorders including neurodevelopmental disorders, drug addiction and cancer. They are present on the cell membrane and contain a large extracellular region, through which adhesion GPCRs interact with other diverse proteins. The mechanics of how adhesion GPCR interact and function are poorly understood, hampering progress in understanding their biological roles and mode of action. My previous work has shown for the first time that up to four copies of the adhesion GPCR latrophilin assemble together when bound to two unrelated proteins (FLRT and Unc5).

I now aim to understand how adhesion GPCRs regulate the development of brain tissue and blood vessels. My goals are to reveal further details on the structures and functions of latrophilin assemblies with their partners, find out how these direct brain cortex development, reveal how additional brain molecules control latrophilin functions, and understand how latrophilin and other adhesion GPCRs function in blood vessels. 

The results will reveal fundamental new insights into the roles of adhesion GPCRs in tissue formation and disease.

Professor Steven Sinkins

University of Glasgow

Wolbachia-mediated arbovirus inhibition in mosquitoes

Viruses transmitted by mosquitoes impose huge health burdens in countries with a tropical climate. There are millions of cases of dengue fever annually and it can be fatal, while the very painful and debilitating chikungunya fever is rapidly expanding in range and epidemic severity. The recent emergence of Zika virus was declared a global health emergency by the World Health Organization and it poses new concerns for pregnant women because it has been linked to birth defects and neurological disorders. Options for controlling these diseases remain very limited.

All three of these viruses are transmitted by Aedes mosquitoes. One way to control the viruses involves Wolbachia bacteria, which can be introduced into the Aedes mosquitoes and can block virus transmission when present at high levels. If these bacteria are to be used as disease control agents, it is important to understand the mechanisms by which they prevent virus transmission. We will examine at what stages of the viral life cycle inhibition occurs for all three viruses, and examine the effects of Wolbachia on various mosquito pathways that we predict could have an influence on virus cell entry or replication.

Dr Matthew Towers

University of Sheffield

How is embryonic development timed and scaled?

How do cells know how long they need to divide to allow structures such as limbs to grow to their correct sizes?

We will work on the developing chick wing bud to test if two molecules – one that tells the cells to divide and one that tells them to stop dividing – form the mechanism of a growth/size clock. In this hourglass timer model, the level of the molecule that tells cells to stop dividing increases until it passes a threshold that stops cell division and growth. We will also test if these growth clocks can be reset to an earlier time in the embryo. We will also investigate why different species have differently sized limbs. We will ask if limb growth clocks run at species-specific rates in a range of birds of different sizes, including quails, chickens and ducks. Understanding how these clocks function can give insights into human disorders in which the timing of embryonic growth is disrupted.

If we can use this information to reset limb clocks later in adults and reset development, we might be able to devise clinical strategies to aid limb regeneration.

Dr Jim Usherwood

Royal Veterinary College

Advance, inform, test, refine and exploit the Muscle/Mechanical Compromise Framework

For an animal to perform an action economically, it must have the mechanics and the conditions for the muscles correct. There are often conflicting demands in much of animal locomotion. A new framework allows exploration of the muscle/mechanical compromises, providing fundamental accounts for anything from human leg forces during walking and running, to why sparrows flap their wings in a different way to eagles.The aim of this project is to inform and advance the models to incorporate changes of energy through incline and decline locomotion and differences in muscle properties, and how these can vary with training, development, age, size and species.

Mice trained to run under hypergravity in a centrifuge will be used to investigate the capacity for muscle and gait mechanics to adapt when operating with a reduced ‘time’. Birds of a range of size and species (from quail to ostrich) and ages (chick to subadult ostrich) will demonstrate scaling of muscle properties and gait mechanics. We will test the effect of inclusion and changes in energy on the motions and the oxygen consumption of humans using sloping treadmills. Large populations will be measured walking at science fairs and running at running clubs to differentiate the effects of age and size.

Dr Mark Walton

University of Oxford

Dopamine regulation of action initiation and self-control

The brain chemical dopamine is known to be vitally important for motivation and decision-making and whether an action is worth taking. The amount of dopamine correlates with the expected benefits of a reward. Moreover, a lack of dopamine has been linked to apathy while too much dopamine can cause impulsive behaviour. However, why this is the case is still poorly understood. One way to investigate the role of dopamine in the brain is to manipulate it using drugs. But while the effects of drugs can last for hours, dopamine release can happen in a fraction of a second.

I will be using new technologies to record and disrupt moment-by-moment dopamine in animals as they perform tasks requiring them sometimes to take action and other times to refrain from taking action in order to gain rewards. I will therefore be able to determine the direct relationship between real-time dopamine release and taking or withholding actions.

This research will provide new insights into impulsivity and motivational disorders.

2012-2015

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A

Dr Ivan Ahel

University of Oxford

Protein poly(ADP-ribosyl)ation in genome stability and human disease

Ivan is a biochemist at the Sir William Dunn School of Pathology, University of Oxford. His laboratory employs biochemistry, cell biology, X-ray crystallography and animal models to study cellular responses to DNA damage. Ivan is particularly interested in understanding the pathways and proteins regulated by ADP-ribosylation, a post-translational protein modification known to be involved in DNA repair, modulation of chromatin structure, mitosis, transcription and apoptosis.

Dr Julie Ahringer

University of Cambridge

The regulation of chromatin structure and function

Professor Fred Antson

University of York

Structure and mechanism of nucleic acid-processing machines in viral biogenesis

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Professor Stuart Baker

Newcastle University

Subcortical contributions to primate forelimb movement

Stuart’s research examines how brainstem and spinal circuits contribute to the control of movement in primates, including man, with a special focus on the upper limb and hand movements. As well as experiments which investigate how these centres function in healthy animals and humans, he is interested in how these subcortical systems are involved during recovery after brain lesions, such as stroke or spinal cord injury. Stuart’s lab mainly uses electrophysiological methods in human volunteer subjects and in awake behaving monkeys, and is interested in novel mathematical methods for analysis of neural data.

Dr Paul Bays

University of Cambridge

Noise in neural codes: consequences for memory, exploration and decision making

Professor Timothy Behrens

University of Oxford

Neural mechanisms of behavioural control

Tim is interested in the neural mechanisms that control behaviour: how features of the world are represented in our brains; how these representations change during learning; and how they constrain behaviour. Such questions are difficult because they require access to complex patterns of neuronal activity which are difficult to obtain in humans, but also because of the rich behavioural repertoire that is difficult to study in animal models. Therefore, a major goal of the Fellowship is to develop sophisticated imaging techniques and computational analyses to get closer to human neuronal codes, and to validate and compare these against neuronal codes measured in animal models.

Dr Louise Boyle

University of Cambridge

Molecular mechanisms controlling peptide selection for immune recognition

Professor Michael Briggs

Newcastle University

Defining disease models in mouse models of chondrodysplasia

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Dr Jonathan Chubb

University College London

Jonathan is interested in the regulation of gene transcription. His lab takes a modern approach that allows them to see the dynamics of transcription of single genes in living cells, in real time. This has revealed that transcription occurs as a series of irregular pulses or bursts. They are combining this imaging technology with molecular genetics and computational modelling to understand the mechanistic basis of the pulsing process. The ability to view transcription in living cells also gives a unique window into how cells regulate gene expression during developmental decisions. Unlike more conventional, static approaches, this can allow a cell to be observed before, during and after it makes a gene expression decision, which, combined with image analysis tools to extract the salient features of the cell and its microenvironment, gives unprecedented resolution into the way cells make choices.

Professor Jane Clarke

University of Cambridge

Multidisciplinary studies of protein folding, misfolding and assembly

Jane is a biophysical chemist who is interested in the fundamental link between protein sequence, structure, function and interactions. The evolved primary sequence of a protein does not simply encode its final structure, but also the pathway by which it folds, how it avoids misfolding and the functional dynamics. Currently Jane’s research team (of biochemists, chemists and physicists) are using a multidisciplinary approach, combining ensemble and single molecular kinetic and equilibrium methods, structural tools, protein engineering and computer simulations to investigate folding, misfolding and assembly of large multidomain proteins, which make up over 75% of human proteins.

Professor Heather Cordell

Newcastle University

Development and application of statistical methodology for the detection and characterisation of genetic factors in complex disease

Heather is a statistical geneticist based in the Institute of Genetic Medicine, Newcastle University. Heather’s research focuses on the development and application of new and existing statistical approaches for analysing human genetic data, with the aim of uncovering causal relationships between genetic factors and disease-related outcomes. Heather is involved in a number of applied studies, most notably genome-wide association studies, in disease areas as diverse as primary biliary cirrhosis, vesicoureteric reflux, visceral leishmaniasis and atopic eczema. In addition to her applied work, Heather develops methods for family-based data (including maternal and parent-of-origin effects), and for modelling multiple loci (including interaction effects) simultaneously.

Dr Sarah Coulthurst

University of Dundee

Deployment, consequences and utility of bacterial effectors

Sarah is a molecular microbiologist based at the College of Life Sciences, University of Dundee. Her research aims to understand how pathogenic bacteria utilise protein secretion systems and other virulence factors to interact with eukaryotic host organisms or competitor bacteria. Current work is focused on the widespread ‘Type VI secretion system’ and the nature and importance of the effector proteins that it secretes. Considering the system from the molecular to the population level aims to provide new insights, which can ultimately be translated towards new antimicrobial therapies.

Dr Colm Cunningham

Trinity College Dublin

Reconciling cholinergic and inflammatory hypotheses of delirium: the acute and lasting effects of systemic inflammation on chronic neurodegeneration

Systemic inflammation and neurodegeneration-associated neurotransmitter imbalances can combine to produce significant deleterious consequences for the vulnerable brain. The main focus of Colm’s Fellowship is to understand how the loss of influence of acetylcholine, a neurotransmitter, can leave the degenerating brain susceptible to inflammation-induced cognitive dysfunction, including delirium, and can accelerate the progress of neurodegenerative disease. The work sits at the interface of neurodegeneration, neuroinflammation and experimental psychology and is aimed at identifying key processes through which systemic inflammation exerts its deleterious effects on the brain, in order to minimise the significant impact of inflammation on the vulnerable brain.

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Professor Ilan Davis

University of Oxford

The mechanism of mRNA transport and localised translation during axis specification and synaptic plasticity

Ilan’s group focuses on elucidating the post-transcriptional mechanisms that regulate pattern formation in the oocyte and neural stem cell division and renewal. They combine genetics, biochemistry, transcriptomics and advanced live cell imaging and image analysis methods to study these processes in Drosophila. They are investigating the RNA signals and associated RNA binding proteins of gurken, which encodes a TGF-alpha signal and defines the anterior-posterior and dorso-ventral axes, and Prospero, a transcription factor that is the key to determining neural stem cell fate. Ilan is the director of Micron, an interdisciplinary hub focusing on super resolution microscopy.

Professor Simon Davis

University of Oxford

Principles of early T-cell activation

Simon's laboratory strives to obtain insights into immune function by trying first to understand how the relevant molecules behave. Simon’s research has taken this approach because it constrains the possibilities for thinking about what the molecules might actually be doing. His work therefore relies for the most part on structure- and single-molecule imaging-based approaches. Simon has explored the mechanism of weak, specific recognition at cell surfaces, established the molecular composition of the T-cell surface and, with Anton van der Merwe, proposed a counter-intuitive explanation for how the T-cell receptor initiates immune responses, called the kinetic-segregation model.

Professor Simon Draper

University of Oxford

Harnessing human antibodies to deliver effective immunoprophylaxis against difficult disease targets

Dr Ian Duguid

University of Edinburgh

Neural representations of movement in primary motor cortex

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Dr Fumiko Esashi

University of Oxford

How do proliferating human cells maintain genome integrity?

Fumiko’s research goal is to understand how proliferating human cells guard their genomic DNA against various stresses coming from the environment and from normal processes of cell growth. She focuses on investigating homologous recombination (HR), which can provide error-free repair of DNA breaks, but can also alter genomic DNA if engaged inappropriately. Building on her earlier discoveries that central cell cycle drivers play important roles in the dynamic regulation of HR, her current work aims to elucidate how HR is activated at the right time and at the right location, and how erroneous recombination events are suppressed.

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Dr Andrew Firth

University of Cambridge

Encyclopedia of RNA virus elements: systematic bioinformatic discovery and experimental analysis of hidden genes, non-canonical translation mechanisms and other functional elements in RNA virus genomes

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Professor Anton Gartner

University of Dundee

Combined genetic and biochemical approaches to uncover and characterise redundant factors involved in late stages of recombinational repair

Anton uses C. elegans as a model organism to study basic biological problems. Homologous recombination is needed for error free DNA repair and for meiotic recombination. Holliday Junctions are crucial recombination intermediates first postulated to exist more than 40 years ago. Anton focuses on how these junctions are processed both during recombinational repair and during meiosis.

Professor Anna Gloyn

University of Oxford

Bridging the gap from type 2 diabetes genetics to functional mechanisms of disease

Anna's research is focused on the translation of genetic association signals for type 2 diabetes and glycaemic traits into molecular, cellular and physiological mechanisms. Anna is particularly interested in integrating genetic association data with human islet transcriptomic and genomic data to identify mechanisms for pancreatic islet dysfunction. Her work is highly translational and supports efforts to improve our ability to interpret genetic variation in genes implicated in diabetes risk, and to identify effective therapeutic targets for drug development. Anna is an active member of a number of international consortia investigating the genetic basis of type 2 diabetes and related glycaemic traits.

Professor Ian Goodfellow

University of Cambridge

Unravelling the networks that determine and control norovirus infection and pathogenesis

Professor Alexander Gourine

University College London

Alexander studies central nervous mechanisms of cardiovascular and respiratory control. Interacting neural networks of the brainstem continually adjust our breathing and activity of the heart and blood vessels to meet the physiological and behavioural demands of the body. Until recently, glial cells called astrocytes have been thought to merely provide active neuronal networks with structural and nutritional support. However, new experiments suggest that astrocytes are actively involved in brain information processing and control of complex behaviours. Current research aims to understand the fundamental principles underlying astroglial influences over brain networks controlling breathing and cardiovascular activity.

Professor Kay Grünewald

University of Oxford

Membrane modulation in crucial virus-host interactions

Professor Mads Gyrd-Hansen

University of Oxford

Identification of atypical ubiquitylation and its role in inflammatory signalling

Mads is a molecular biologist based at the Ludwig Institute for Cancer Research, University of Oxford. Mads studies the molecular mechanisms governing proinflammatory signalling during innate immune responses, with particular focus on bacteria-sensing pattern recognition receptors (PRRs). Through this, he aims to uncover the molecular switches that on one hand protect against invading pathogens but that also contribute to chronic inflammation and cancer. His current work focuses on delineating how the establishment and regulation of ubiquitin modifications control a cell’s proinflammatory response to PRR stimulation, with a particular focus on the signalling properties of individual ubiquitin linkage types.

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Dr Suzana Hadjur

University College London

Cohesin proteins bridge genome topology and function during development

Professor Simon Hay

University of Oxford

Defining the population at risk and burden of disease of Plasmodium vivax malaria

Simon investigates spatial and temporal aspects of mosquito-borne disease epidemiology to support disease burden estimation and the rational implementation of disease control. The aim is to generate evidence-based tools (often maps) to support public health decision making at the global scale. Having established new mapping platforms for Plasmodium falciparum malaria, his work now addresses the more neglected human malaria parasite Plasmodium vivax. During the Fellowship this has also expanded to consider P. knowlesi malaria. Overcoming the unique biological complexities of P. vivax and the human genetic polymorphisms associated with infection susceptibility and treatment are the new challenges of his Fellowship renewal.

Professor Lora Heisler

University of Aberdeen

Metabolic consequence of in vivo modulation of discrete serotonergic pathways

Obesity and type 2 diabetes represent major medical and economic challenges for the 21st century. Unfortunately, obesity medications are limited, reflecting a profound worldwide unmet clinical need. Lora’s research aims to elucidate the mechanisms underlying the development of obesity and type 2 diabetes in an effort to identify novel therapeutic interventions. The brain is the master regulator of energy balance and body weight, and Lora’s laboratory studies the neural underpinnings of appetite, energy expenditure, adiposity accumulation and glucose homeostasis. A particular emphasis of the research programme is the neurotransmitter serotonin, which has been a target of obesity medications for over 20 years. The research team is delineating the mechanism through which serotonin medications improve obesity in an effort to identify more targeted interventions. Lora’s laboratory also discovered that a specific component of the brain serotonin network improves type 2 diabetes and her group is further defining how this effect is achieved.

Dr Brian Hendrich

University of Cambridge

Transcriptional control of stem cell fate

The goal of Brian’s research is to understand how control of transcription facilitates lineage commitment of stem cells in early mouse development. To do this he is studying how chromatin modifying, transcriptional regulatory multiprotein complexes influence gene expression patterns as cells undergo developmental transitions. This involves investigating how gene expression heterogeneity within a population of cells is controlled and how it influences cell fate decisions. Additionally he is studying how these chromatin remodelling complexes interact with the transcription machinery to influence chromatin configurations and to modulate transcript levels.

Dr Patrick Heun

University of Edinburgh

The role of nucleoplasmin in genome organisation and stability

A major focus of Patrick's research is to understand how chromosomes are organised in the cell nucleus. Specific genomic regions occupy distinct regions in the nucleus in many different organisms. Using Drosophila as a model, he showed that centromeres cluster together and associate with the nucleolus. This organisation depends on a network of factors associated with the protein NLP of the nucleoplasmin/phosmin family. A perturbation of this subnuclear architecture correlates with impaired genome stability. Patrick's lab currently aims to understand the molecular underpinnings of centromere positioning and dissect the functional role of the factors that mediate it.

Dr Jonathan Houseley

Babraham Institute

Mechanisms of environmentally stimulated copy number variation

Dr Ian Humphreys

Cardiff University

Modulating cytokine expression by T cells to protect the mucosa from chronic viral infections

Ian studies immune responses to viruses. Effective antiviral immunity at mucosal surfaces is critical for the restriction of transmission, persistence, and pathogenesis of viral pathogens. His research seeks to identify immune pathways that protect mucosal tissue from infection, and to understand the role that cytokines play in regulating these responses. Using an integrated approach, involving both human clinical specimens and in vivo models of virus infection, he hopes to identify how to modulate cytokine production by T cells in order to improve antiviral protection of mucosal tissue.

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Dr Andrew Jackson

Newcastle University

Overcoming the scientific and technological barriers to long-term incorporation of neuroprostheses into motor networks

Professor Heidi Johansen-Berg

University of Oxford

Structural brain changes with learning and recovery from stroke

Heidi investigates how the brain changes with learning, recovery from damage, or changes in lifestyle. She uses a variety of neuroimaging methods, such as FMRI or EEG, to monitor brain changes. She uses methods such as brain stimulation or neurofeedback to try to augment brain change. Most of her work is on human volunteers, including both healthy individuals and people who have had stroke. Some studies use rodents so that microscopic measurements can be used to understand the basis for the observed changes. Through better understanding of brain change, Heidi hopes to be able to design new interventions to improve recovery after damage, or boost resilience to brain decline.

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Professor Robert Klose

University of Oxford

Understanding the role of CpG islands in gene regulatory element function and transcription

Despite every cell in our body having essentially the same genetic information, individual cell types can achieve highly specialised functionality through their capacity to utilise defined subsets of genes. In understanding the fundamental mechanisms that underpin this normal gene regulation, Rob’s research is focused on discovering how CpG island gene regulatory elements, which are associated with most human gene promoters, exploit chromatin-based and epigenetic mechanisms to specify normal gene expression programmes. This new understanding will provide a basis to explore novel avenues for therapeutic intervention in instances where CpG island function is perturbed in human disease and cancer.

Dr Alexander Kraskov

University College London

Cortical and subcortical mechanisms underlying movement generation and inhibition: a view through the mirror neuron system

Alexander studies the mechanisms of movement generation and inhibition. His unique approach is to investigate brain activity during action observation when no movements are executed despite the presence of significant activity within the brain motor network. By answering the question of what the brain mechanism is which prevents us from moving while observing others, he hopes to offer novel insights into both the command signals that do characterise motor execution and the mechanisms for suppression of unwanted movements, a key feature of human behaviour.

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Dr Gareth Lavery

University of Birmingham

Regulation of NAD+ metabolism in skeletal muscle during ageing and disease

Gareth’s research group is at the Centre for Endocrinology Diabetes and Metabolism, University of Birmingham. Their work seeks to understand skeletal muscle signals and processes that mediate the health benefits of exercise along with important nutritional compounds. The aim is to define the properties of these processes and target them as a strategy to stave off the increasing incidence of metabolic and age-related decline and disease. Identifying ways to retain healthy, functional skeletal muscle that can maximally benefit from exercise and nutritional interventions will be important to support ageing societies.

Professor Clare Lloyd

Imperial College London

Epithelial-immune interactions underlying development and resolution of allergic airway inflammation and remodelling influence of genes and environment

The central theme of Clare’s work explores the interactions between resident lung cells and infiltrating inflammatory cells in order to determine how these interactions influence the development and resolution of pulmonary inflammation. The lab uses a mixture of in vivo mouse models and in vitro culture systems using cells from patients to investigate the mechanisms underlying the pulmonary immune response to inhaled allergens and pathogens. The current focus is predominantly how the genetic background of an individual and the external environment influences epithelial-immune interactions, particularly with respect to infection history and development of allergic immune responses in early life.

Dr Sally Lowell

University of Edinburgh

Differentiation competence of pluripotent cells

The aim of Sally's work is to understand how pluripotent cells select particular lineages as they exit pluripotency. There is considerable variability between individual cells in the way they respond to differentiation cues, for reasons that are currently not well understood. Sally is exploring the idea that changes in cell adhesion influence the way that cells integrate information from their environment. The hope is that understanding this level of regulation will help to resolve the apparent unpredictability of the differentiation response.

Professor David Lyons

University of Edinburgh

Using zebrafish to study myelinated axons in vivo

The goal of David's Fellowship is to elucidate the biology of myelinated axon formation. Myelinated axons comprise about half the volume of our brain and spinal cord and the presence of myelin on axons is essential for nerve impulse conduction and long-term axonal health. It is well known that disruption to myelinated axons contributes to numerous diseases and it is now becoming clear that new myelin can be made throughout life, most likely to fine-tune nervous system function. David's laboratory uses live imaging, genetic and chemical biology approaches in zebrafish to discover the currently unknown mechanisms of myelination in vivo.

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Dr Craig MacLean

University of Oxford

The evolutionary biology of antibiotic resistance

Dr Annette MacLeod

University of Glasgow

Genetic determinants of host/parasite interactions in African trypanosomiasis

The zoonotic disease human African sleeping sickness occurs as a result of the parasite jumping the host species barrier and infecting humans. This is followed by interactions with the host to cause disease. The central question of Annette’s research is: how does naturally occurring genetic variation in both the host and the parasite result in variation in disease susceptibility and severity? Moreover, can this knowledge about host/parasite interactions be used to develop new therapies to combat the disease? Annette is exploiting the recent advances in sequencing technology to address these questions using population genomics.

Dr Mairéad MacSweeney

University College London

Using deafness as a model system to inform literary intervention and neurobiological models of language

Mairéad investigates how the brain processes language. She addresses this issue by primarily working with people who have a very different language and sensory experience compared to the rest of the population – those born profoundly deaf. Research with this group allows a unique perspective on how experience shapes the brain which cannot be gained from studying hearing people alone. This basic research can also inform evidence based practice. Deaf children typically find it very difficult to learn to read. In Mairéad’s current work she is testing a reading intervention for deaf children which is based on her past behavioural and neuroimaging research.

Professor Adele Marston

University of Edinburgh

The role of the pericentromere in mitosis and meiosis

Adele aims to understand how chromosomes are transmitted to the next generation during cell division. Her group currently investigates fundamental molecular mechanisms that operate from the kinetochore and surrounding chromatin, the pericentromere, to ensure the accuracy of chromosome segregation. A particular focus is to understand how the chromosome segregation machinery is modified for the production of healthy gametes during meiosis. Ultimately, this will help to identify the underlying origins of aneuploidy, a major cause of infertility and birth defects.

Professor Markus Meissner

University of Glasgow

Essential or redundant: dissection of apicomplexan invasion mechanisms

Markus’s research focuses on the mechanisms involved in the invasion of the host cell by apicomplexan parasites. In order to invade, the parasite evolved a whole set of unique secretory organelles that are formed during the intracellular development of the parasite. Using Toxoplasma gondii as a model system, his group investigates the biogenesis, maintenance and regulation of these organelles. The research goals include identification and analysis of essential genes linked to invasion and modulation of the host cell using forward genetic screens. The group developed several reverse and forward genetic tools that allow the systematic dissection of essential genes in apicomplexan parasites. The group is also investigating host cell factors required for the growth of the parasite to understand the interdependence between the parasite and its host.

Dr Anne Mitchell

University of Oxford

Characterising neural networks of thalamo-cortical interactions important for cognition in primates

Professor Yorgo Modis

University of Cambridge

Cell entry and innate immune recognition of enveloped viruses

Yorgo’s overall goal is to understand at the molecular level how enveloped RNA viruses, including important pathogens such as dengue and Rift Valley fever viruses, assemble and deliver their genomes into the cell. Other related aims of his research are to understand how viral RNA is recognised by the innate immune system, and to map the evolutionary origins of the genes that drive virus entry. By integrating a complementary set of biophysical, biochemical and cell biological approaches, Yorgo’s long-term vision is to obtain complete mechanistic models with atomic-level detail of the processes of virus cell entry and innate immune recognition.

Professor Andrew Morris

University of Liverpool

Statistical methods for the analysis of genome-wide association and re-sequencing studies

The theme of Andrew’s research is the development, evaluation and application of novel statistical methodology for the analysis of the ‘next generation’ of genome-wide association studies (GWAS) of complex human traits. His research considers common and rare genetic variation from diverse ethnic groups, interrogated through traditional GWAS genotyping arrays, supplemented by imputation, and through state of the art whole-exome or whole-genome re-sequencing studies. The methodology is being applied to GWAS of a range of complex traits, with a focus on cutting edge studies investigating the genetic basis of type 2 diabetes and related metabolic phenotypes, endometriosis, and response to pharmaceutical drugs.

Dr Janaina Mourao-Miranda

University College London

Learning from neuroimaging and clinical data: a multiple-source machine learning approach for mental health disorders

Janaina is an engineer and neuroscientist who leads a research group at the Computer Science Department, University College London. Her research focuses on developing and applying machine-learning models to investigate complex relationships between neuroimaging data and multidimensional descriptions of mental health disorders. More specifically, Janaina’s research investigates the following questions: can we learn about underlying brain mechanisms of mental disorders from these relationships? Can we better stratify patient groups based on these relationships? Can we combine information from clinical assessments with different neuroimaging modalities to build better diagnostic and prognostic models of mental health disorders?

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Professor Stuart Neil

King’s College London

The molecular and cellular basis for the function of the HIV-1 Vpu protein in the targeting of host antiviral and immune-modulatory factors

Stuart’s lab investigates the role of HIV-1 accessory proteins in the replication and pathogenesis of HIV/AIDS. These proteins modulate host immune responses and are essential for viral replication and spread in vivo. The HIV-1 Vpu protein counteracts the antiviral membrane protein Tetherin that restricts viral release and acts as an innate immune sensor. Vpu also targets other cell surface molecules involved in immune regulation, and appears to downregulate proinflammatory signalling through the NFkappaB pathway. Understanding the molecular and cellular basis of Vpu function and the relevance of its target molecules for HIV pathogenesis are the central aims of Stuart’s Fellowship.

Dr Sergey Nejentsev

University of Cambridge

Genetic and functional mechanisms of susceptibility to mycobacterial infection

Sergey is studying human genes involved in resistance to infection. Mutations in such genes may lead to immunodeficiencies and predispose to infectious diseases, such as tuberculosis. Discovery of these genes helps to uncover novel biological pathways that mediate immune responses and may suggest new targets for intervention. Sergey and his group use methods of human genetics, including genome-wide association studies, exome- and whole-genome sequencing, in vitro models of infection, and methods of molecular biology to understand underlying immune mechanisms protecting from infection.

Professor Thomas Nichols

University of Warwick

Transforming statistical methodology for neuroimaging meta-analysis

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Professor Andrew Oates

University College London

Patterning embryos with genetic oscillations

Professor Hiroyuki Ohkura

University of Edinburgh

The specialised apparatus for meiotic chromosome segregation in oocytes

The focus of Hiro's research is to understand chromosome segregation and mis-segregation in oocytes. Genes must be passed on accurately from cell to cell and from parents to children. Errors in chromosome segregation in oocytes are a major cause of infertility, miscarriage and birth defects in humans. This error-prone division has many features distinct from mitosis, but little is known about the molecular mechanism. Using Drosophila oocytes, Hiro's lab currently investigates how chromosomes and the spindle are built and how they interact with each other at a molecular level using a genetics-led multidisciplinary approach.

Professor Tom Owen-Hughes

University of Dundee

Mechanisms for remodelling chromatin

Tom’s main area of interest is to understand how chromatin structure is reconfigured during gene regulation. A topic of special interest is the action of ATP-dependent nucleosome remodelling enzymes related to the budding yeast Snf2 protein. At one level Tom investigates the mechanisms of these molecular machines using structural and biochemical approaches. Genomic approaches now provide a powerful means of assessing function both in model organisms and humans where Snf2 related proteins are linked to a variety of diseases including cancer.

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Professor Nancy Papalopulu

University of Manchester

Studying neurogenesis through developmental time

Dr Andrew Plested

University College London

Optical control and report of synaptic transmission

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Professor Juri Rappsilber

University of Edinburgh

Protein structures in the context of time and space by mass spectrometry

Juri wonders if protein structures could be studied in the native context of the proteins. He uses cross-linking/mass spectrometry (CLMS), an approach his lab helped to pioneer during his previous Fellowship. CLMS already forms part of an integrated structural biology approach. Now, Juri hypothesises that CLMS can generate structural insights into currently difficult targets of structural biology. In particular, he investigates MeCP2, a protein with important biological functions in the context of chromatin, but whose structure cannot be determined in isolation.

Professor Blanca Rodriguez

University of Oxford

Safety and efficacy of anti-arrhythmic drug therapy in acute myocardial ischaemia in human: an integrative, multiscale and mechanistic investigation

Blanca is Professor of Computational Medicine in the Department of Computer Science, University of Oxford. Blanca’s interest is in investigating the causes and modulators of variability in the electrophysiological response of the heart to disease and therapies, with a specific focus on anti-arrhythmic therapy in acute myocardial ischaemia in humans. Understanding variability in cardiac response to disease, drugs or mutations is key to ultimately determining who may be at risk, when and how, and how to improve their diagnosis and treatment. Mechanisms underlying cardiac activity are complex, multiscale and non-linear, involving numerous multiscale feedback loops from gene to whole body level. Blanca’s team combines computational modelling and simulation with experimental and clinical research to overcome the challenges involved in dissecting the key mechanisms underlying cases potentially as lethal as cardiac arrhythmias.

Professor Gloria Rudenko

Imperial College London

Molecular mechanisms mediating immune evasion in African trypanosomes

Gloria investigates African trypanosomes, which cause African sleeping sickness. Trypanosomes provide a very manipulable experimental system for investigating the molecular machinery behind pathogenicity. Gloria would like to understand how these extracellular parasites are so effective at immune evasion, and the role of the protective VSG coat in this process. She has a particular interest in gene expression and has been focusing on the role of epigenetic factors in transcriptional control. In addition, she is investigating the molecular biology behind the synthesis of the VSG surface coat. Hopefully, this research will help us understand why trypanosomes are such effective pathogens.

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Dr Eric Schirmer

University of Edinburgh

The role of tissue-specific nuclear envelope proteins in cytoskeletal and genome organisation in development and disease

Eric’s research is focused on understanding the roles of tissue-specific nuclear envelope transmembrane proteins (NETs). In particular he is using genome-wide approaches to determine the genes at the nuclear periphery in different tissue differentiation systems and how the spatial position of these genes changes along with their expression with knockdown of NETs that affect gene/chromosome position. For the cytoskeleton he is testing NETs that alter cytoskeletal organisation and looking at tissue-specific cell polarity, cell migration, mechanotransduction and cell mechanical stability. These NETs and the functions being elucidated may help explain the tissue-specific pathologies of dozens of nuclear envelope-linked diseases.

Dr José Silva

University of Cambridge

Defining the mechanisms of induced pluripotency

Professor Steven Sinkins

University of Glasgow

Wolbachia as a tool for the control of mosquito-borne disease

The main focus of Steven's research group is Wolbachia, an inherited intracellular bacterium, and its interactions with mosquitos. Wolbachia can manipulate host reproduction by inducing crossing sterility known as cytoplasmic incompatibility (CI), allowing rapid population spread. It occurs naturally in many mosquito species and can also be artificially transferred from other insects. Certain introduced strains can strongly inhibit the transmission of mosquito-borne viruses such as dengue and parasites such as Plasmodium (malaria). Current work focuses on the mechanisms of virus inhibition and CI, and how they can be used for disease control.

Professor David Strutt

University of Sheffield

How do cells coordinate their polarity in multicellular tissues?

David is a developmental biologist interested in pattern formation and morphogenesis, with a particular focus on understanding how cell polarity is coordinated between neighbouring cells in developing tissues. Primarily using epithelial morphogenesis in the fruit fly Drosophila as a model system, his lab studies the mechanisms by which two conserved pathways, the ‘core’ planar polarity pathway and the Fat/Dachsous pathway, mediate cell-cell communication and cell polarisation. His current work has a strong emphasis on understanding the role of protein dynamics in coordinated cell polarisation, using genetic, cell biological and computational methods.

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Dr Ilias Tachtsidis

University College London

Early bedside biomarkers of cognitive function following neonatal brain injury

Problems during birth can lead to a lack of oxygen reaching the brain and cause brain injury. Ilias is developing instrumentation and methods to monitor the status of the injured brain non-invasively at the infant's cot. Ilias’s instruments utilise a technique called NIRS that uses low light levels to measure the distribution of oxygen and blood in the brain and how oxygen is being utilised by cells. Ilias’s instruments and methods are able to monitor the metabolic status of the brain tissue by measuring the status of the cytochrome-c-oxidase, an enzyme found in mitochondria, the power factory of the cell.

Dr Sandra Telfer

University of Aberdeen

Zoonotic disease risk in Madagascar

Zoonoses transmitted from wildlife pose an increasing threat to human health. Sandra’s research addresses both fundamental and applied questions related to host-parasite dynamics in reservoir populations and exposure rates in human populations. A current focus is comparing rodent-borne zoonoses with contrasting transmission routes (plague, leptospirosis, hantavirus and rickettsioses). She is working with the Institut Pasteur de Madagascar to examine how climate and land use influence the abundance of infected reservoirs, and to establish how vulnerability to zoonoses in human populations is influenced by both environmental and socio-economic factors. The work combines field studies, genetic analyses and modelling.

Professor Greg Towers

University College London

Characterisation of host-virus interactions

The central hypothesis of Greg’s lab is that successful viral infection requires evasion of the defensive processes that constitute the intracellular innate immune system. Their aim is to understand the host-virus interactions that manipulate or evade innate immunity and dictate infection outcome. Current projects focus on viral nucleic acid detection and evasion of DNA sensing by the HIV-1 capsid protein. The lab also studies viral proteins that specifically antagonise sensing to provide mechanistic insight into sensing activation and its consequences. They take a multidisciplinary approach that combines molecular virology and genetics with medicinal chemistry, X-ray crystallography and NMR spectroscopy.

Dr Ellie Tzima

University of Oxford

Mechanotransduction in physiology and cardiovascular disease

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Dr Jim Usherwood

Royal Veterinary College

Jim's fellowship is exploring the mechanical and physiological costs and constraints imposed on animal locomotion: why we find walking and running so tiring; why we cannot run faser or further; and why we use more flexed leg postures when small or when running. The approach taken is to make small additions to the most reductionist models of economic gaits, and to test the model predictions across species, through development, and with mechanical manipulations such as hyergravity. For this, Jim's lab has developed a four metre animal centrifuge and force-sensing rodent wheel.

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Dr Seralynne Vann

Cardiff University

Importance of mammillary body connections for memory

Seralynne’s research primarily investigates the neural basis of episodic and spatial memory. The mammillary bodies were the first brain structure to be implicated in memory but over the years their importance has often been overshadowed by the hippocampus. Seralynne’s research programme focuses on the mammillary bodies, and their connections, and aims to understand what they contribute to memory. Seralynne uses a convergent approach combining behavioural neuroscience, electrophysiology and neuropsychology to address the key questions at a multidisciplinary level.

Dr Lidia Vasileva

University of Oxford

The role of the nuclear exosome complex in RNA regulation

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Professor Scott Waddell

University of Oxford

Neural mechanisms of memory, motivation and individuality

Learning permits animals to convert innate reflexive behavioural responses into meaningful stimulus-guided actions. Scott studies how sensory-motor transformations are implemented and altered in the nervous system. His research uses genetic, anatomical, physiological and behavioural approaches in the fruit fly Drosophila to understand these neural mechanisms at cellular resolution. Current interests include dopaminergic control of reward learning and of hunger- and thirst-motivated behaviours. Scott’s group also identified neural transposition in the fly brain and study how the resulting genetic heterogeneity might contribute to organismal individuality.

Dr Chris Wallace

Cambridge Institute for Medical Research

Partitioning autoimmune diseases on their molecular basis

Dr Simon Walker-Samuel

University College London

Modelling barriers to drug delivery and response to therapy in solid tumours using non-invasive magnetic resonance imaging

Simon is developing techniques for quantifying the structure and function of tumours using magnetic resonance imaging (MRI). MRI can be sensitised to the motion of water, which allows the structure of tissue to be probed via the restriction of water diffusion. Similarly, convective flow is used to quantify fluid flow within blood vessels, alongside abnormal flow between tumour cells. By characterising fluid dynamics and tumour structure, the overall aim of his research is to quantify and predict barriers to successful drug delivery.

Dr Andrew Welchman

University of Cambridge

Decoding dorsal depth processing in the human brain

Andrew studies the computational and neural mechanisms that support visual and multisensory perception. His work integrates behavioural measurement, computational modelling and brain imagining to quantify sensory processing within the human brain. His Fellowship is focused on the mechanisms that support three-dimensional perception, and involves developing computational brain imaging to reveal the way in which three-dimensional signals enhance perception. This includes understanding how judgements improve when multiple signals are used in combination, and how training boosts perceptual decisions and modifies neural processing at short- and longer-term timescales.

Dr David Withers

University of Birmingham

ILC3 control of adaptive immune responses

Dr Charles Wondji

Liverpool School of Tropical Medicine

Tackling insecticide resistance in the major African malaria vector Anopheles funestus: developing new molecular diagnostic tools, understanding the evolution of resistance and its impact on control interventions

Insecticide based control interventions are critical for malaria prevention. However, insecticide resistance in malaria vectors threatens the continued effectiveness of these tools. To help manage such resistance, Charles’s research aims at understanding its molecular and genetic bases by detecting molecular resistance markers using genomic tools and designing suitable molecular assays to track resistance in natural populations. He is also defining patterns of gene flow and selective sweeps in populations of malaria vectors to predict the evolution and spread of resistance and is assessing the fitness cost of resistance and its impact on control interventions using experimental hut trials in Africa.

Professor Will Wood

University of Bristol

Drosophila embryonic macrophages as a model system for studying migration and bacterial infection in real time

Will’s research investigates the molecular machinery that underlies innate immune cell migration in vivo. Using the genetically tractable model Drosophila melanogaster, Will’s lab use genetics and live imaging to explore how macrophages are able to migrate within the complex environment of a three-dimensional living organism. One current focus is how these immune cells prioritise competing cues, such as damage signals released from wounds and ‘eat me’ signals arising from apoptotic corpses, as well as the guidance cues that direct their developmental dispersal during embryogenesis.

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Dr Philip Zegerman

University of Cambridge

Regulated replication initiation in genome stability and development

Professor Magdalena Zernicka-Goetz

University of Cambridge

Regulation and dynamics of progressive cell fate transitions and morphogenesis during development of the early mouse embryo

Magdalena aims to understand the key events directing development of the mammalian embryo from the time of fertilisation until gastrulation. She uses an integrated approach that combines classical and molecular embryology with genetics and imaging techniques. These aim to uncover the epigenetic modifications and cellular mechanisms that are crucial in setting aside the embryo’s natural stem cells, the epiblast, from two neighbouring extra-embryonic tissues, trophectoderm and primitive endoderm. More recently she has developed culture techniques that allow the epiblast and its two neighbouring tissues to develop in vitro through stages that until now have been hidden from view as the embryo implants into the uterus. This has given new insight into a previously unrecognised ability of the epiblast to respond to surrounding extra-cellular matrix and self-organise into a rosette like structure, essential for the formation of the fetus.

People we've funded

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