I’m curious how you transitioned, after, I don’t know if you would say solving the main mechanics of transport of protein and COP-I COP-II, the sec genes involved. How did you find something after that that you wanted to continue researching?
Well that’s a very good question. What I did was just sort of accidental, I started switching from yeast to mammalian cultures and continued for some years to study those pathways in mammals in circumstances that were physiologically quite distinct or relevant to disease. And so that was a natural, really easy transition, the same kinds of approaches–but not really genetics.
Then maybe seven or eight years ago I started looking around for other avenues of membrane traffic for which I felt there were opportunities using a biochemical approach that had not been explored well enough in other laboratories. And so I had some people looking at autophagy, the mechanism of autophagy, where the membrane originates in autophagy. I had another subset looking at traffic from the golgi apparatus to the lateral surfaces of a polarized epithelial cell. I had several people looking at unconventional secretion where small proteins are secreted out of the cell independent of the standard secretory pathway. And I felt as we were doing this that we were making interesting findings, but it was not the kind of focus that I feel fits my personality. I really like to focus. And so beginning now at around that time, I had a terrific graduate student join the group who was interested in this business of extracellular vesicles, and that’s become the focus of the group now.
And I think that was a good choice because again I could bring my intuition and my approach to this problem in a way that no one else in the field had done, using a biochemical approach. And so it’s been okay; I don’t think we’ve hit a real home run yet because although we’ve been able to figure out how RNAs get sorted into these vesicles as they’re sorted inside the cell–to some extent we’ve figured it out, we have a way of studying it–we haven’t really quite cracked what I think is the real question which is what this banquet proposal is about which is why do cells make these things and are they being delivered for some functional purpose. I really believe that must be true, but it may not be easily recapitulated in vitro, in cell culture. I prefer to work with cells and not with animals, but there must be a way to do this with some specialized cell culture technique that we have yet to apply.