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Hooked on research
  1. Clare Bryant

Abstract

Clare Bryant was recently appointed professor of innate immunity at Cambridge veterinary school, making her the first woman to become a professor in the department. Here, she explains how it came about

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I WAS born and bought up in Cornwall. As a child I used to carry my dad's medical bag when he worked as a GP and apparently I was very good in a crisis. I always said, however, that I wanted to be a vet not a doctor, much to his consternation. Growing up in a Cornish village I was totally embedded in the farming community, but, was also horse-mad and had a cat so my animal interests were very broad. My parents were good friends with Owen Pearce from the St Columb veterinary practice, so I saw of lot of practice early on.

All of this convinced me I wanted to be a vet, but I got a little distracted around my A-levels so I did not get the grades to immediately get into vet school. At the time this was a devastating blow, but I now know that it was the best thing that could have happened to me. Off I went to Southampton university to do biochemistry and physiology with the key aim of getting a good degree to go to vet school through the graduate intake. After a merry couple of years I got a summer job as a researcher and it was like somebody switched a light on in my head: I became totally addicted to research. On returning to Southampton I cut the merriment and really started to work academically hard for the first time in my life. I relished my honours practical project, met my future husband and got a good degree. I was torn at that point between pursuing a PhD or going to vet school, but after a lot of excellent advice from friends in science, I followed my first love to train as a vet at the Royal Veterinary College (RVC) always bearing in mind that the PhD option would still be there at the end of my veterinary training.

Clare Bryant (centre) with her research team; the group recently discovered how cat allergens trigger inflammation

Research during summer vacations

During my veterinary degree I became very interested in pharmacology and anaesthesia (which I think of as pharmacology and physiology in motion). The research bug, however, remained firmly entrenched and I spent two vacations working on summer projects in industry. In my final year at the RVC I applied for, and was lucky enough to receive, a Wellcome Trust funded studentship to pursue a PhD with Kathy Clarke, working on species differences in alpha2 adrenoceptor biology.

I spent my first summer after graduating in general practice, then started my PhD, regularly locuming in practice when I wasn't doing research work. It quickly became apparent that I wanted to do a lot of fundamental pharmacology studies in horse tissue so I needed access to a horse abattoir. At this time there were only two within the UK and the nearest was in Bristol. David Lodge, at the RVC, helped me to find lab space with Alex Livingston in Bristol so I could collect the tissues from the abattoir on a Monday morning and then work on them for three days in the empty teaching labs during the university vacations.

Fortunately, my long-suffering parents-in-law lived close to Bristol, so I lodged with them while I was working with Alex. This in vitro work led to some novel observations about which receptors were activated by medetomidine, later confirmed in work at the RVC. I was now completely hooked on research. I also learnt from Alex about how I would like to run a lab, that is, to have a research group of scientists, vets and medics working together to solve fundamental scientific problems and to translate those findings to humans and other animals.

I then gained a Wellcome Trust postdoctoral fellowship, after significant help from Jonathon Elliot, to work at the RVC and with the Nobel laureate, Sir John Vane, at St Bartholomew's Hospital. This was a wonderful opportunity to learn about internationally competitive science and it sparked my life-long interest in shock, sepsis, inflammation and infection. I made important friends and colleagues, particularly Jane Mitchell and Tim Warner, who gave me invaluable help and support in my early career. Working in Sir John's lab was an education at all levels, particularly in learning to be a very through scientist and how to present well at meetings. I learned not to be afraid of questions at the end of talks because it was unlikely that anyone would ever ask me a more difficult question than those that came from Sir John.

At this time, I also started to work with Rod Flower, a great mentor and friend, with whom I have happily worked for many years understanding how the corticosteroid-inducible protein annexin 1 regulates cellular responses to endotoxin. One thing I thought a lot about whilst I was at Bart's was how to translate fundamental biology into comparative studies. There are many reagents for human and mouse research, but few for anything else. I received a good basic grounding in molecular biology skills from Robert Hannon and realised that this was the best way forward for my comparative research. It is relatively easy to generate molecular reagents to any species!

Reliance on grants

It was at this stage in my career that I began to understand that, while research is fantastically interesting it is also very stressful. You are only as successful as your last paper and life in academia revolves around your ability to obtain money from different funding bodies. Experiments are expensive: if you don't get grants you cannot do experiments.

My salary was also coming from my grant so this meant constantly thinking about life in terms of three- or four-year blocks of time, depending upon how long you can get the funding to support yourself. Ian McConnell and Polly Taylor encouraged me to move to Cambridge and I was again lucky to get a Wellcome Trust Research Career Development Fellowship. This was for work focusing on annexin 1 regulation of endotoxaemia in horse, mouse and human cell models. A fundamental part of this fellowship was to embed clinical anaesthesia training into my working life so, while driving my research, I also completed the certificate in anaesthesia that I had started with Kathy Clarke at the RVC. Almost as soon as I arrived at Cambridge, Duncan Maskell appeared. We immediately realised that we had complementary interests; Duncan mutated the bacterial genes that synthesise endotoxin, whereas I worked on the cellular responses to endotoxin. We started collaborating and this work has formed the basis of much of my current research work.

Soon after starting to work on infection, the toll-like receptors (TLRs) were discovered. These proteins recognise bacteria and are potentially important therapeutic targets for human and animal diseases. Our work on the role that pattern recognition receptors such as the TLRs play in infectious diseases of humans and other animals is the central theme of my research. I also started to work on structure-function analysis of TLRs with the structural biologist Nick Gay from the biochemistry department in Cambridge. In this work we use species differences between how horse, mouse and human TLRs recognise bacterial components to determine the structural requirements that allow the receptors to signal. The added bonus of this work is that it allows us to understand the structure of horse TLRs such that the design of highly selective antagonists becomes possible.

The mentorship I have received at Cambridge from Duncan and Nick has been instrumental in helping me to grow as a scientist and to gain research funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC), the Wellcome Trust and the Horserace Betting Levy Board. During this time I became a university lecturer at the vet school and a fellow of Queens' College. I was therefore fully immersed into the world of teaching vets, medics and natural scientists everything I could about pharmacology – it was a steep learning curve for all of us.

Wellcome fellows are encouraged to travel and, as a consequence, I have spent a lot of time abroad, particularly in the USA. This has been a fantastic way to live and work in another country for short periods of time. My research has been transformed by working with my colleagues abroad and I have loved every minute of it. It is a privilege to have made friends around the world and some of them, particularly Jim and Cynthia Moore at the University of Georgia, David Underhill in Los Angeles, Kate Fitzgerald and Doug Golenbock at the University of Massachusetts and Luke O'Neill at Trinity College Dublin, are like a second family to me. I continue to travel a lot, and to stay on top of my research it is essential that I continue to meet the experts in my field. Five minutes with any of my international colleagues often saves me months of experimental work.

Most recently I have become interested in thinking about the dynamics of how cells become infected (working with Julia Gog from the department of applied mathematics and theoretical physics) and the physical process of cellular infection (with Pietro Cicuta from the department of physics). I gained a BBSRC fellowship to focus on this work, which is nearing completion. Working with scientists from different disciplines has been hugely rewarding because I have had to learn new languages and to think about things in totally new ways. Many things I thought were technically impossible are not. For example, we can even pick up live bacteria with laser tweezers and feed them to cells to monitor the infection processes.

My work is on zoonotic bacteria trying to understand the similarity and differences in how humans and domestic animals respond to infection. Why some bacteria are pathogens in one species but effectively commensals in others remains unknown. We also work on animal allergens and recently discovered how cat allergen triggers inflammation (www.bbc.co.uk/news/health-23436589).

I am lucky enough to have a great research group comprising vets, medics and basic scientists investigating these problems using a range of multidisciplinary techniques. I was made one of the founding diplomats of the European College of Veterinary Pharmacology and Toxicology and I attend weekly small animal medicine ward rounds where we engage in lively discussions about rational drug choices in the clinic. My recent promotion to professor of innate immunity makes me the first woman to become a professor at the Cambridge veterinary school. The fact that it has taken a while to appoint a woman as professor in my department, which is predominantly staffed by women, may seem odd, but the promotion system in Cambridge is based within the school of biological sciences rather than at departmental level. This means that promotion is dependent on how competitive your research track record is compared to the other candidates in the school. I am very excited to be a professor in this ancient university staffed by so many brilliant people and I often have to pinch myself to believe its really me, a girl from a Cornish comprehensive school, who is here.

Broadly speaking, I wouldn't want to change anything in my career. I would like to be more diplomatic and life would have been much less stressful had I been less driven, but that's not the way I am made. I would probably have had more career opportunities in research if I studied medicine so my dad was right after all, but I enjoy being a vet and it brings a unique insight to my research career. In particular many opportunities have been missed when thinking about comparative biology: the lessons to be taken from the diseases we see in domestic animals are highly informative for medicine, but sometimes it's a struggle convincing doctors to think about things in species other than knock-out mice!

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