Researcher Spotlight: Professor Margaret Robinson
Professor Margaret “Scottie” Robinson holds a Wellcome Trust Principal Research Fellowship and is a Professor of Molecular Cell Biology and the Cambridge Institute of Medical Research. Here she tells us about her research, eukaryotes, cakes and clathrin…
What are you working on?
I’m interested in the organisation of cells like our own – that is, eukaryotic cells, which are filled with lots of different membrane compartments, as opposed to prokaryotic cells like bacteria, which have only surface membranes. What’s particularly fascinating is that eukaryotic cells are able to form all these different compartments, each of which is made out of a distinct set of molecules, and then they send molecules from one compartment to another, without everything getting mixed up.
We work on proteins called adaptors, which collect the right types of molecules from a particular compartment and package them into little carriers called coated vesicles, which then deliver the molecules to a different compartment.
It turns out that there are a lot more different types of coated vesicles and adaptors than we’d originally thought, so we’re trying to find them all and figure out what they do and how they work.
What does your average day involve?
I wish I could say doing experiments, but I don’t spend nearly as much time at the bench as I’d like to.
An average day would be divided between spending time in my office, mainly writing or reviewing (papers, grant applications, PhD theses, project reports…), and spending time in the lab talking with people about their results. There are normally 3-4 postdocs and 2-3 students in my lab, and every two weeks we have a group meeting in which we all show our data, exchange ideas, and enjoy homemade cakes.
But the best days are when I get to do some research with my own two hands.
Why is your work important?
Partly because it’s so fundamental – every form of eukaryotic life on earth – animals, plants, fungi, and unicellular eukaryotes – contains coated vesicles and adaptors, and it’s been speculated that this machinery played a key role in the evolution of eukaryotes from prokaryotes over two billion years ago. Our work also has medical implications, although these weren’t at all apparent when I first started working on coated vesicles nearly 40 years ago.
Some adaptors are mutated in certain genetic disorders, and adaptors are frequently exploited by pathogens. For instance, the HIV genome encodes a protein called Nef, which is essential for the development of full-blown AIDS, and which works by hijacking adaptors and using them to modify the surface of the infected cell.
What do you hope the impact of your work will be?
I hope our work will not only help to explain how coated vesicles sort cargo, but also provide tools that can be used by others to address their own favourite problems. For instance, we developed a new method that we call a ‘knocksideways’.
The idea was to get rid of proteins rapidly, instead of slowly as in a knockdown or a knockout, because cells are very good at compensating for the lack of something if you give them enough time to adjust.
The knocksideways technique has turned out to be very useful for another lab, who are interested in how particular proteins contribute to different stages of cell division, and I hope there will be many other applications as well.
How did you come to be working on this topic/in this field?
I became captivated by cell biology as an undergraduate, because of all the amazing structures that could be seen by electron microscopy. At that time, there were lots of descriptive studies, but almost nothing was known about what these structures were made of or how they worked.
Then as a PhD student I got interested in “the sorting problem” – why all the compartments in the cell don’t get mixed up – and it seemed as though coated vesicles might hold the key. The other reason I decided to work on coated vesicles is that they are absolutely gorgeous, particularly clathrin-coated vesicles, where the clathrin forms a lattice around the vesicle with the same sort of geometry as a football. That was in the mid 1970s, and I’ve been working on coated vesicles ever since.
How has Wellcome funding helped you/your research/your career?
I’m fortunate enough to have been funded almost exclusively by the Wellcome Trust for 25 years now, right from the time I first set up my own lab, and they’ve been exceptionally supportive.
What’s the most frequently asked question about your work?
What’s that thing that looks like a football?
Which question about your work do you most dread – and why?
Is your work going to lead to cures for diseases? It’s always tricky when doing basic science, because it sounds a bit frivolous to say that the main reason we work on coated vesicles is that we think they’re incredibly interesting, but I’m afraid it’s true. Having said that, one of the most rewarding things about our work is that we’ve stumbled upon a number of clinical connections, so maybe in the (very) long run our work might actually lead to cures.
Tell us something about you that might surprise us…
I’m a keen knitter, and one of my projects was to make a clathrin hat for a PhD student in the lab who was about to undergo chemotherapy for Hodgkin’s lymphoma and was expecting to lose most of her hair. As it happened, she hardly lost any hair at all. But the best news is that she made a full recovery and is now a Sir Henry Wellcome Fellow in Paris. (And she still has the clathrin hat.)
What keeps you awake at night?
When I have to give a talk the next day. But at least I’ve managed to get over throwing up every time I have to give a talk, which is what I used to do.
What’s the best piece of advice you’ve been given?
When I first moved to an independent position as a Wellcome Senior Fellow, back in 1989, all of the other independent investigators in my department were men, and nearly everyone assumed that I must have been working for somebody else – even when I told them otherwise. It was very frustrating, and I used to come home every evening and complain to my husband (who is also a scientist) that nobody seemed to believe I was my own boss. He would tell me not to let it get me down, but to carry on doing my best work, and eventually people would get the message. My response at the time was, “It’s all very well for you,” but of course he was right.
The “chain-reaction” question set by our previous spotlit researcher Prof Daniel Pick is this: What led you to agree to be spotlit?
I like to fly the flag for basic science – not just our own work, but curiosity-driven research in general, because you never know where it may lead.
You can find out more about Prof Robinson’s work on her lab page and you might also like to read her papers: Characterisation of TSET, an ancient and widespread membrane trafficking complex and A human genome-wide screen for regulators of clathrin-coated vesicle formation reveals an unexpected role for the V-ATPase. For more information about the types of funding that the Wellcome Trust offers, see the funding pages of our website.