Professor Michael Rossmann wins the 2017 Prize Medal
04 April 2017
Today at the Microbiology Society’s Annual Conference 2017, Professor Michael Rossmann from Purdue University will be awarded our Prize Medal for his outstanding contributions to the development of protein crystallography and understanding of virus structures.
You can see Michael’s lecture at 09:00 in the Pentland Suite, Level 3. You can also see an informal interview with Michael at 19:00 on the Society’s stand in the Lennox Suite, Level -2.
When did you first become interested in science?
I was born in Germany, but I grew up in England and went to a boarding school in Saffron Walden, Essex. There was a science teacher there – Mr Pumphry – when I was in the lower 4th form who taught us regular lessons in a laboratory, which I rather liked. As I progressed through the school I became the lab curator and got to know the set-up rather well.
At school there was also a club room where we built radios – this was towards the end of the Second World War. I was able to get all the news on the radio I built, and people would gather round to hear the latest bulletins.
After gaining your PhD at the University of Glasgow, you moved abroad again, this time to the US. How was that?
I went to the University of Minnesota to do a postdoc, and I learnt about computing. Electronic computers were completely new then. The Honeywell Company, based in the neighbouring city of St Paul, had one of the first commercial computers. The university got permission to use the computer, and my boss Bill Lipscomb – who went on to win a Nobel Prize – realised that the computer could do some of the crystallography calculations that were normally done by hand. This became really important in the crystallography field later on.
You were initially working as a physicist to solve the bond lengths between atoms. How did you move into biology?
I was at a meeting in Montreal in around 1957, and I heard a presentation by Dorothy Hodgkin who was talking about the work of John Kendrew and Max Perutz – all three who would also go on to win Nobels. She was talking about their efforts to solve protein structures; although I barely knew what a protein was, I was trained as a physicist!
What attracted me to the field was the size of the problems to be solved – to fix atoms in space. I wrote to Dorothy and Max, asking whether I could join them in their research.
What was that like?
In Cambridge, in Max Perutz’s lab, we were based in a little hut outside the Cavendish Laboratory. The people there were terrific – Max, John, Frances Crick and Sidney Brenner – more Nobel winners!
Every morning at 11 o’clock we would have coffee and talk about the problems we were working on. Francis and Max had a big impact on me. They showed me that there’s more to science than just solving little problems – you need to look at the bigger picture. This was a change that happened gradually without my knowing.
Did you find it difficult to move from one discipline to another?
It had happened before. My undergraduate degree was in physics, while my PhD was looking at organic molecules. I knew very little about them when I started – in those days, a physicist learnt about ‘high energy physics’, known to most now as ‘particle physics’.
I just followed what was interesting. In Cambridge I did take a course in Biochemistry – I sat in with the undergraduates because I knew I was ignorant about the subject. I probably still am in many ways! By the time I finished in Cambridge and moved to Purdue University, I was certainly aware that the world of biology contained some very interesting things.
You’re well known for your work on virus structures.
Actually, one of the places where I think I’ve contributed more than anything is developing the molecular replacement method, or MR as it’s known (which wasn’t a coincidence!). There are over 100,000 protein structures in the databanks, three quarters of which used MR for their determination. The other thing that people might know me for is a protein structure I call the nucleotide binding fold, although others call it the Rossmann fold.
When I went to Purdue University I wanted to work on viruses because they had some of the symmetrical properties that I was exploring when developing MR. I thought that the methods I’d been developing computationally could be used to solve virus structures, and it turned out I was right.
In 1985 you published the structure of rhinovirus-14, the first common cold virus to be solved. Can you tell us about that?
That was actually the first virus structure that used MR. The structure was extremely informative as it suggested how the virus worked. From a computational point of view this was a watershed moment for solving virus structures and allowed lots of other people to take up the work.
You mention that the structure alluded to the function – was this something you expected?
It sort of all fell in my lap – seeing the canyon in the virus and recognising that this might be the attachment site, which was later found. Shortly after that, the site known as the ‘pocket factor’, which can be replaced by antiviral compounds, was shown to be an important place for viral stability. It was nice to see all of these things come together, and these findings gave rise to more experiments.
There’s been an explosion in viral structures; how does a viral structure help to prevent disease?
To make a vaccine you need to attenuate the virus, but keep the surface the same so that antibodies can bind. How can you do that? There are lots of examples of viruses being passaged and mutating sufficiently to be used as a vaccine – yellow fever vaccine was developed this way, for example.
Our work allows us to see what these mutations are doing in the yellow fever virus, and we can apply it to Zika, something we’re working on at the moment. You can’t see what mutations are doing without a structure; when you’re working without one, you’re working blind.
What technical challenges remain with obtaining crystals for structural biology?
Actually we’re a bit past that now, and we don’t really deal with crystallography any more. There’s been a ‘resolution revolution’ and now we tend to use electron microscopy instead, as the detectors they contain have vastly improved.
You’ve been working in this field for many years now. What still excites you about it?
We can do things now with microscopes and computational techniques that allow us to look at individual biological units and see how they change with time. Everybody can recognise a human, but we’re not identical, and it’s the same with cells – they all share the same components but they’re not the same.
Do you think that our ability to see things with greater detail will uncover new secrets about how cells work?
There are lots of secrets waiting to be uncovered, I’m quite sure of that. There’s no such thing as an end of curiosity, in my opinion. We have a very good idea of how molecules and viruses work, although we don’t know all the details. What we can do is start to look at bigger units and how parts of the cell communicate and work together.
What does winning this prize mean to you?
It means a lot. It’s very pleasant to have other people recognise the significance of your work and to know that you’re doing useful things.
Image: Michael Rossman.
