Case study

Jonathan MarchiniProfessor in Statistical Genomics, University of Oxford Collaborative Awards in Science

Getting Wellcome Trust funding

What attracted you to Wellcome and to this scheme?

A group of us based in Oxford, Bristol, London and Cambridge wanted to secure funding for a collaboration that we’d already set up informally – working on the Genomics England dataset for the 100,000 Genomes Project.

We needed to bring together our individual expertise and get postdoctoral support. Wellcome’s Collaborative Award allowed us to do that, and offered a lot of flexibility. 

The amount of funding available was also good – up to £4 million. We didn’t need that much, but it was very generous.

What aspects of the Collaborative Award funding are most useful to you?

The award has helped us to fund the people and the compute power we need to carry out our research. 

I have five people in my research group now, and have money for three postdocs.

What do you think about Wellcome’s application process? 

Before applying, we talked to staff at Wellcome to work out if the project was within its remit. It seemed like they were supportive of the idea in principle, so we went ahead. Having the ability to do that was really useful.

The online application system was pretty straightforward – it led us through the process. 

To prepare for interview we went outside our local contacts to another research institute and got colleagues there to give us a grilling. That was helpful because it exposed some weaknesses in our presentation. I’d recommend having a practice interview at least a week before, so you have time to re-jig things. 

During the interview, the questions were robust but fair. A couple of external experts had been brought in and their questions were very good. It showed that the panel had read our application carefully and thought about it. 

In our presentation, we also included some very preliminary results from the prototype methods. These weren’t in our grant application, so I think that was useful for the panel.  

How challenging have you found it to secure funding?

Securing funding is challenging, and I haven’t always been successful. But that hasn't stopped me from continuing to have ideas and write grants.

When we applied for the Collaborative Awards, it was the first year the scheme had been running. We felt it was good to get in early – maybe some people hadn’t seen the call or got their head round the scheme yet. 

What advice would you give to other applicants?

Talk to as many people as possible beforehand – show them your grant application and get their comments. Do practice interviews – as many as you can.

A few weeks before the interview, we got the peer-reviewers’ comments back. That was very helpful because it gave us some information about what we might get asked in the interview.

Career path

Career summary

  • 2016–present Wellcome Trust Collaborative Award in Science
  • 2014–present European Research Council Senior Investigator Award
  • 2014–present Professor of Statistics Genomics, University of Oxford
  • 2013–present Co-leader, Haplotype Reference Consortium
  • 20052014 Associate Professor of Statistics Genomics, University of Oxford
  • 20022005 Wellcome Trust Research Fellowship in Mathematical Biology, University of Oxford
  • 19982002 DPhil Statistics of MRI Brain Images, University of Oxford

What have been the defining moments in your career so far?

During my PhD, I became aware that data collection in genetics was about to explode. Genome-wide association studies were just on the horizon, and there was a lot of opportunity for methods development.

I was interested in statistical methods applicable to large amounts of data. I’d been working on brain-imaging data for my PhD, but wanted a new challenge. 

In 2002, I got Wellcome’s three-year Research Fellowship in Mathematical Biology. This enabled me to switch fields into genetics.

I’ve been fortunate to work on some high-profile projects, including the HapMap Project, the Wellcome Trust Case Control Consortium and the 1000 Genomes Project. I’m currently co-leading the Haplotype Reference Consortium

These projects have introduced me to the cutting-edge problems in the field. I’ve got to meet and work with lots of good scientists all over the world. 

Research and public engagement

What’s the key question you’re addressing?

We’ll use novel methods to accurately estimate haplotypes (the pair of DNA sequences carried by each individual) from the 100,000 Genomes Project. Then we’ll set up servers that will help researchers to access this data for phasing, imputation and ancestry inference. 

The 100,000 Genomes Project is a government-funded initiative to sequence 100,000 genomes from around 70,000 people. Participants are patients with a rare disease, plus their families, and patients with cancer. The project aims to help uncover the genetic basis of rare diseases and cancer to help with the design of more effective treatments.

How are you going about answering this question?

The large scale of the data and the high-coverage sequencing means that we’ll discover lots of very rare variants and mutations. That’s what’s unique about this dataset. 

The sequencing is being done by Illumina, and we get given the raw data. When we’re estimating haplotypes from the data, we phase each one individually and look for the closest relatives we can in the dataset. The rare variants tell you a lot of information about that. 

The server means that anyone who works in human genetics can take their dataset and compare it to the 100,000 Genomes Project dataset. 

They’ll be able to enhance their own dataset by predicting or imputing variants. It doesn’t matter which disease they’re working on, it will enrich pretty much all the genetic datasets that human geneticists are collecting. 

What public engagement or outreach work do you do?

I regularly get invited to speak at academic conferences. I recently spoke at the International Congress of Human Genetics in Kyoto, and I go to the American Society of Human Genetics meeting most years. 

References 

1. Sharp et al. Phasing for medical sequencing using rare variants and large haplotype reference panels. Bioinformatics doi 2015;10.1093:bioinformatics/btw065.
2. O’Connell et al. A general approach for haplotype phasing across the full spectrum of relatedness. PLoS Genetics DOI 2014;10.1371:journal.pgen.1004234.
3. Delaneau et al. Improved whole chromosome phasing for disease and population genetic studies. Nature Methods 2013;10:5-6.

More information

Find out more about Jonathan's work on the University of Oxford website

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