Professor in Molecular Biology
Department of Biochemistry
Tell us a bit About your role
I am a Professor in Molecular Biology at the Department of Biochemistry, where I manage a young research team. We ask important questions about how the brain works. For example, how do brain cells navigate to find each other within tissues? This is important because cells coming together in the right places is essential for correct brain function. Our work involves cutting-edge research tools available at Oxford, and collaborations with teams elsewhere in the UK and overseas. I also act as a mentor for postdocs and students, sit on the Department’s graduate student committee, contribute to running DPhil programmes and undergraduate teaching, and act as advisor of the student-led society OUBS. At Somerville College, I act as Fellow and Organising Tutor in Biochemistry.
I first became interested in the molecular biology of the brain, when I was working in the lab of Stephen Cusack in France, at the end of my PhD. It was a collaborative project with Dr. Andrew McCarthy. Stephen’s team excels in using the technique ‘protein X-ray crystallography’, a method that was famously advanced by Dorothy Crowfoot Hodgkin in Oxford more than half a century ago. After my PhD I joined the team of Yvonne Jones at Oxford, also using X-ray crystallography and other methods. Yvonne’s team pioneered the production of brain ‘receptor’ proteins using adherent mammalian cell culture. In 2014, I started my own research team funded by the UK’s Medical Research Council and Wellcome Trust at the Department of Biochemistry, in 2017 I was offered a post as ‘Associate Professor and Tutorial Fellow’ associated also with Somerville College, and in 2020 I was awarded the title of professor in molecular biology through the University’s ‘Recognition of Distinction’ Scheme.
My goal is to understand how molecules work within their biological context, especially in the brain. For example, relatively few proteins guide the development of the amazingly complex tissues found in the brain. How these proteins work together in different combinations is still mostly a mystery. The lack of knowledge in the field makes it difficult to treat diseases affecting the brain, such as neurodevelopmental and neurodegenerative diseases. Better knowledge of how specific proteins enable brain function will underpin the rational design of better drugs and treatments for patients suffering from these disorders.
What is the most meaningful aspect of your work?
I find that the most innovative scientific work is often the result of combining ideas from different fields. This allows a researcher to look at a problem from different angles. Working together with other teams to exchange ideas and results, is therefore what I enjoy the most about my work. Earlier this year, my team masterminded a particularly nice study that was done by combining the expertise of four different labs (those of M. Chavent in France - specialising in molecular dynamics simulations, R. Kaufman in Germany - specialising in super-resolution microscopy, R. Klein in Germany - specialising in using mouse models, and my lab in Oxford – specialising in structural and cell biology). We traced the function of three brain proteins at the molecular, cellular and tissue levels and found surprising new insights. The proteins were previously known to function in synapse development, but we found that they also work in a completely different way to help young cells move – a very complicate process that can lead to neurodevelopmental disorders when it goes wrong.
Asking such big questions requires coordinating research projects across different labs with complementary expertise and empowering those researchers that can meaningfully contribute, regardless of where they are. Besides the specific results we found in this study, I find the approach meaningful in itself, as I see the future of medical research going in that direction.
Can you tell us about something you’ve done, contributed to that you’re most proud of?
On a personal level, I am perhaps most proud of the moment I plucked up the courage to walk up to the most prominent researcher in my field at a conference in 2010, to ask if he would collaborate on a new set of results that I had just obtained. Although this may not sound so impressive (lots of people talk to each other at conferences), it was one of the hardest things for me, as was a young and particularly shy ‘postdoc’ at the time. This moment changed my career for good. Not only was it the beginning of a successful collaboration with a brilliant lab (that of Ruediger Klein), but I learned my most important lesson: science is not limited to what the home lab can do! I suddenly felt immense freedom. The real fun is in finding the right tool for the question at hand, and not be limited what one finds close by. I ended up spending several months in Ruediger’s lab, where I learned many techniques that I still use today, and met some of his fantastic co-workers, such as Daniel del Toro (now a group leader in Barcelona). I should add that this big step was only possible because of the support and free rein that Yvonne Jones, my then supervisor, allowed me. In the current climate of scientific funding, where postdocs are hired for specific tasks, this is by no means a given, and I am very grateful to her. This is something that could perhaps be built into the current postdoc supervision process, providing a certain percentage of time to develop their own ideas/work.
What changes would you most like to see in the Medical Sciences in the next 100 years?
Having started my PhD in 2003, I have not yet reached the ‘half-way’ point of my career (I hope) and so my views may still evolve. Here are specific issues where I would like to see a change, from my current point of view:
Research Culture: I would welcome a shift in culture, from an individualistic and often hyper-competitive approach, to a healthy collaborative way of conducting science. Nowadays, big questions are often best approached with team-work and not by big egos working on their own. Team-work also means that many authors contribute to a paper, and so it is important that the contributions of authors are recognised according to how important they were, not just what position they have in the author list. I feel that everyone, including also University recognition panels, should be instructed to take this into account.
Diversity: I am proud to be working in a country where gender and ethnic diversity is taken seriously. I believe the UK has come a long way and has reaped ample awards from using this approach. Our Head of Department (Prof Francis Barr) is one example of an Oxford leader who makes every effort to increase diversity at my Department. This is fantastic, as women and minorities are still strongly under-represented in more senior positions. Besides the types of diversity mentioned above, I would like to see more effort put into creating ‘diversity’ also in terms of different types of jobs. For example, there is almost no funding to provide secure positions for technical research staff. We lose some of our most talented researchers because the short-term-contracts available to them are incompatible with the financial risks that these entail. I would like to see more ‘permanent’ positions for the best of our technical staff.
Funding curiosity-driven research: I hope that the current trend requiring academic research to be ever more ‘applied’, e.g. directly impacting on the economy or human health, will be reversed. Basic curiosity-driven research is important because it provides the knowledge basis that profit-driven entities (such as companies) need to build on. It is therefore essential for the long term future of our economy and health system. As basic research is not aimed at generating profit/impact in the short term, it depends almost entirely on funding by the government or charities. Requesting that academic research caters ever more directly to industry is only a short step away from just using this money to directly support national industries. I think that a clear articulation of long-term benefits to society should be sufficient to justify basic research, but expecting short-term (often fictitious) impact pathways is not helpful.
Research funding more generally: Basic research funds are limited and so it is important to use them effectively. As politics and public opinion are easily swayed, the perceived funding priorities also change quickly. This is a problem because funding continuity is needed to complete projects and to build and sustain centres of excellence. Changing priorities and short contracts mean that researchers on short-term contracts may loose their job without having completed their project and this has ruined many a young person’s career. I therefore believe that funding plans should encompass large time scales, and short grants of just 1-2 years duration should be phased out, unless they are for training only.