Clare BryantProfessor of Innate Immunity, University of CambridgeInvestigator Awards in Science
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Getting Wellcome Trust funding
What attracted you to Wellcome and to this scheme?
I knew about Wellcome as I’d been funded by them in the past. I had a scientific vision, and the Investigator Award scheme seemed like an ideal way in which I could achieve it.
I wanted to carry out long-term fundamental interdisciplinary research and I thought Wellcome would be receptive to this – other funders have very targeted research programmes these days, with an emphasis on translational research. I’m a vet and was keen to carry out comparative studies across a range of animal species. I thought Wellcome’s interest in veterinary research might give me a better chance of getting these aspects of my research vision funded.
It took me a while to pluck up the courage to apply – I wasn’t sure I was good enough. Fortunately, I had supportive colleagues who coerced me into applying. I’d just had a couple of good papers accepted, and one of my previous mentors, Rod Flower, reckons you should always apply just after publishing a strong paper.
What aspects of the Investigator Award funding are most useful to you?
The long-term nature of the funding – five years – is incredibly helpful. It enables me to follow a scientific vision. The scale of funding is also enabling me to build a team to achieve my vision.
What do you think of Wellcome’s application process?
Having been through fellowship interviews before, I knew it would be difficult. The application form was short and has a strong focus on the scientific vision you want to pursue. I put a lot of effort into getting the application right. I asked colleagues to give me feedback on drafts. I trusted them to provide critical comments. Just before I was due to submit, one colleague said: “I love your ideas but I don't like the way they’re presented.” I rewrote my application the weekend before submission.
I also asked international colleagues to check whether what I was proposing was novel and genuinely competitive. I knew Wellcome was likely to use international reviewers, so I wanted to be sure that what I was suggesting would stand up on an international stage.
I did a lot of preparation for my interview. I twisted the arms of my long-suffering colleagues to do dummy interviews. The interview itself was hugely challenging. You’re only allowed a ten-minute presentation with three slides. You can’t use transitions or fancy stuff like movies, which I normally rely on. There was a roomful of people – I can’t recall how many – but two led the questioning. I just tried to concentrate on the individuals asking the questions.
Afterwards, I thought it had gone OK – could have been worse, could have been better. A couple of weeks later I got an email with the subject ‘You got it no cuts’, which was wonderful.
How challenging have you found it to secure funding?
I’ve had three Wellcome fellowships and in 2001 I applied for a Wellcome Trust Senior Research Fellowship. I had an interview but didn’t get it. It was pretty devastating but made me re-examine what I was doing. Scientifically, I changed direction slightly.
A Biotechnology and Biological Sciences Research Council ‘buy-out’ research development fellowship enabled me to hand over my teaching responsibilities and collaborate with physicists and mathematicians. This has been incredibly fruitful and helped form the basis of my Investigator application. So there can be life after a rejection.
What advice would you give to other applicants?
Go for it. I suspect women, in particular, may feel they’re not good enough and lack the confidence to apply. Get as much input as you can from people who have received similar funding. Use your colleagues and external contacts to get feedback, and benchmark yourself internationally. Do practice interviews. They’re ghastly when you make a complete fool of yourself in front of colleagues but they’re vital preparation.
- 2015 Sabbatical, Genentech
- 2015 Wellcome Trust Investigator Award
- 2013 Professor of Innate Immunity, University of Cambridge
- 2009 Reader in Immunopharmacology
- 2007-08 Sabbatical, Trinity College Dublin, Republic of Ireland, and University of Massachusetts Medical School, Worcester, USA
- 2003 Lectureship in Clinical Pharmacology, University of Cambridge
- 2001 Sabbatical, University of Georgia in Athens, USA, and Institute of Systems Biology, Seattle, USA
- 2000–03 Wellcome Trust Research Advanced Fellow, University of Cambridge
- 1996–2000 Wellcome Trust Research Career Development Fellowship, University of Cambridge
- 1995–96 Research scientist, St Bartholomew’s Hospital Medical College, London
- 1992–95 Wellcome Trust Junior Training Fellowship, Queen Mary, University of London, and Royal Veterinary College
- 1989–92 Wellcome Trust Research Training Scholarship, Royal Veterinary College and Bristol University
What have been the defining moments in your career so far?
I don’t have children but am married to someone working in industry the south-east of England. This has restricted the range of institutions I can work at.
I really wanted to do a postdoc in the USA, but that simply wasn’t possible. Instead, I’ve had a series of incredibly fulfilling sabbaticals in the States. They’ve opened my eyes to how Americans do science and transformed the way I respond to challenges. I’m far less cautious now and far more willing to say, “Yes, let’s give it a whirl.” The sabbaticals also greatly expanded my international networks.
Not getting the Wellcome senior fellowship was painful. but had I been successful I wouldn’t have got the buy-out fellowship. It opened a new chapter in my research career - one door closed but another one opened. I guess it turned out fine in the end.
Research and public engagement
What’s the key question you’re addressing?
I’m interested in understanding cellular mechanisms of ‘innate immunity’ – the initial non-specific recognition of pathogens. In particular, I work on Toll-like and NOD-like receptors. These recognise and bind to specific structural features on invading bacterial organisms. They also bind to allergens, triggering harmful inflammatory reactions.
How are you going about answering this question?
I’ve been fortunate to work with some fantastically talented postdocs, biochemists, microbiologists, mathematicians and physical scientists. We’ve developed a host of new techniques to investigate intracellular interactions. We use novel imaging techniques and apply structural approaches to visualise what’s going on.
My goal is to continue developing these multidisciplinary approaches to answer fundamental questions about inflammatory biology. Working with fantastically such clever people in physics and mathematics has been one of the most exciting aspects of my career by a long way.
- Walsh C et al. Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa. J Immunol 2008;181(2):1245-54.
- Herre J et al. Allergens as immunomodulatory proteins: the cat dander protein Fel d 1 enhances TLR activation by lipid ligands. J Immunol 2013;191(4):1529-35.
- Fowler CJ et al. Abnormal nasal nitric oxide production, ciliary beat frequency, and Toll-like receptor response in pulmonary nontuberculous mycobacterial disease epithelium. Am J Respir Crit Care Med 2013;187(12):1374-81.
- Man SM et al. Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA 2014;111(20):7403-8.
- Man SM et al. Actin polymerization as a key innate immune effector mechanism to control Salmonella infection. Proc Natl Acad Sci USA 2014;111(49):17588-93.
Find out more about Clare's work on the University of Cambridge website.