Case study

Michael DustinDirector of Research, Kennedy Institute of Rheumatology and Professor of Molecular Immunology, University of OxfordPrincipal Research Fellowships

Getting Wellcome Trust funding

What attracted you to Wellcome and to this scheme?

I was working at New York University (NYU) when Marc Feldman from the Kennedy Institute asked whether I might be interested in moving to new labs being built in Oxford. This appealed to me greatly and I could see how I might be able to take my research in a new direction. The move was quite complex, and was a partnership between Oxford, the Kennedy Institute and the Wellcome Trust. I knew something about the Trust already as I’d been involved in assessing Principal Research Fellowship applications (PRFs). We sent a brief outline of what we’d like to do and were invited in for further discussions. It was clear the PRF route offered a way to support my relocation.

What aspects of the PRF funding are most useful to you?

The seven years’ support is a huge bonus - it takes a couple of years to get a new lab up and running. The fact the PRF provides a full package of support – salary and research expenses – is another big plus. And it takes account of salary differentials between the USA and UK. All in all, it’s an outstanding funding package. It’s also very flexible. For example, we were able to route transitional salary support for relocating postdocs through Oxford to NYU.

What do you think about the application process?

After our initial discussions, I entered the standard PRF application route. This was a risk – if I wasn’t successful the whole move would collapse. So I had to put in a competitive application. We had plenty of dialogue with the Trust, which was helpful given the complexities of the move. Oxford colleagues were also very helpful. I think everyone wanted to give my application the best chance to succeed. The application itself is relatively short, given the scale of funding. It’s very vision-led. I’d been on the other side of the table for the interview process, so I knew what to expect. 

How challenging have you found it to secure funding?

The Trust was the only UK funder we approached. I knew the competition would be tough, but I thought with my track record and our exciting new direction I had a good chance of success.

What advice would you give to other applicants?

Talk to people at the Trust. They’re aware of the challenges and what it means to move country. They’re open to dialogue, honest and will point you in the direction of the most appropriate scheme. They aim to smooth the process so your application stands or falls on the quality of the science. The process is suited to targeted recruitment. In the USA, it’s more normal to apply to a few centres and then identify which is the best fit for what you want to do. In the UK, it’s more about different partners working together to achieve a specific aim. It’s riskier – you may not get the fellowship – but has many advantages. I received a lot of support from Oxford during my application, including dry runs of interviews. It was very helpful preparation – it’s not something you can just wing.

Career path

Career Summary

  • 2014 Director of Research, Kennedy Institute of Rheumatology
  • 2013 Professor of Molecular Immunology, University of Oxford
  • 2001 Research Professor, New York University
  • 1993–2000 Associate Professor, Washington University in St Louis
  • 1990–93 Postdoctoral fellow, Washington University in St Louis
  • 1985–90 PhD, Harvard Medical School

What have been defining moments in your career so far?

Our characterisation of the immunological synapse, and its validation of our artificial platform for studying interactions between T cells and other immune cells [1], was a pivotal movement. Moving to the UK was a big step. When I mentioned the possibility to my wife, who’s also a scientist, I wasn’t sure how she’d react. She was intrigued. When we were training, our mentors had often spent time abroad as part of their training. But with so many opportunities in the States, training abroad went out of fashion. This felt like a missed opportunity. Now we have a chance, later in life, to experience another culture we’ve admired from afar.

Research

What’s the key question you’re addressing?

I’m interested in understanding the mechanisms of the immunological synapse. It’s a structure created when T cells bind to target cells (B cells, antigen-presenting cells or cells targeted for destruction). This structure is crucial to signalling between cells and pivotal to the control of immune responses.

How are you going about answering this question?

We’ve reconstituted the immunological synapse on a novel artificial platform, which we use to study molecular events. Using imaging and other approaches, we examine signals exchanged between cells and how this affects subsequent immune responses.

What achievement are you most proud of, in research or more generally?

When I was a graduate student, I had a lecture on endothelial activation by cytokines. I’d been working on a cell adhesion molecule, ICAM1, and wondered whether it might be involved. I was on a lab rotation with Tim Springer and he pulled a few strings so I could get hold of some cytokines. This was before you could just ring up and order them. I went around Boston with an ice bucket picking them up, along with fibroblasts to test them on. We found that ICAM1 is indeed strongly upregulated by cytokines [6]. That’s still my most highly cited paper. 

References

  1. Grakoui A et al. The immunological synapse: a molecular machine controlling T cell activation. Science 1999;285(5425):221-7.
  2. Davalos D et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005;8(6):752-8.
  3. Kim JV et al. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 2009;457(7226):191-5.
  4. Shaw TN et al. Perivascular arrest of CD8+ T cells is a signature of experimental cerebral malaria. PLoS Pathog (in press)
  5. Choudhuri K et al. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 2014;507(7490):118-23.
  6. Dustin ML et al. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 1986;137(1):245-54.

More information

Find out more about the work of Michael's group on the Kennedy Institute of Rheumatology website

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