I started my career with the MB/PhD programme – clinical and research training in one course – at the University of Cambridge. I really enjoyed it.
I did an undergraduate research project with the immunologist Doug Fearon at Cambridge, which was really inspirational. My PhD was with Michael Neuberger at the MRC Laboratory of Molecular Biology (LMB). During my time in his lab Michael made some of his most important discoveries about antibody evolution, it was an extraordinary time!
Then I went back into medical training, specialising in nephrology. Many will know that medical training in the UK is not necessarily easy to combine with academia, but eventually I secured a starter grant from the Academy of Medical Sciences to do a part-time postdoc with Felix Randow at the LMB.
I subsequently managed to get a four-year MRC clinician scientist fellowship to start my own small group in the Virology division in Cambridge building on the work I did in Felix’s lab. I was very lucky to recruit a superb postdoc, Rachel Ulferts, who has moved to the Crick with me. I also established a great collaboration with Oliver Florey’s group at the Babraham Institute.
Felix’s interest was in antibacterial autophagy, a process by which cells identify and destroy bacteria by packaging them up into cellular compartments. I started to look at how cells react to being infected by viruses, specifically influenza, rather than bacteria.
When influenza invades a cell, it makes an acid channel which interferes with the cell’s pH balance. During my postdoc I discovered that this acid channel binds to an essential autophagy protein. We thought this might block autophagy, but my group later showed that the interaction isn’t fundamentally to do with autophagy but a related process that we know very little about. So now we’re trying to find out what that process is, what it’s for and why influenza triggers it when infecting a cell.
There’s lots of undiscovered cell biology for us to work on. Immediate goals are to work out which elements of the autophagy machinery are required for this newly discovered process and which aren’t, and what the other components of the pathway are. Then we have to work out why the pathway exists and why influenza cares about it so much. The great thing about working on viruses is they tend to target the really important processes in a cell, so they can help us find out what those are.
The minute you start investigating cell biology you find things you never expected to find. So who knows where we’ll be in six years’ time!
Even without the great building and facilities, the environment for what I want to do is second to none here. There are so many groups working on autophagy, immunity and influenza biology, and I’m right in the middle of that Venn diagram.
I also want my research to be driven as much as possible by biological questions rather than availability of technology. This environment really lets you explore that fully and being able to access the in-house expertise in the science technology platforms is very important.
For someone who’s a clinical academic – where historically fellowships have been fairly short term – the fact that the Crick is giving a relatively long time is also an enormous attraction.
We’re setting up the lab at the moment and we’re exploring different microscopy techniques for live cell imaging to look at the real-time formation and behaviour of influenza infected cells.
People have been mostly very friendly and the new group leaders have been socialising together. I also found that we had some outstanding candidates in the recent round of PhD recruitment, and I’m really looking forward to them joining the lab.
There’s a big challenge of going from a small group to having more people and needing to delegate properly. Tying in my clinical work as a nephrologist at the Royal Free Hospital to what we are discovering about inflammation and infection is another challenge.
A very strong cup of coffee!
A philosopher maybe, though I like doing something directly useful as well as interesting. Or a singer perhaps – I still sing quite a lot, as a bass in an ensemble specialising in 16th and 17th century music. I’m not good enough to make it in opera though…
