Randy Schekman — The Bulletin Board Goals

LC: So I heard that a way you motivate people is a bulletin board in your lab with major landmark and achievements on it that you’re shooting for. I was wondering if this board is still literally or figuratively in place and what your current research goals are. 

RS: Oh absolutely, I have a new posting which I put up a couple of years ago which has yet to be claimed. I don’t pick things that can be done on an annual basis. I pick things that sometimes take many years to achieve, lofty goals that apply to more than one person in the group. And we have only had, I don’t know, seven or so in my career. So they don’t happen too often. 

So yeah I have another one up, a challenge. I don’t know, you know I think my group took these more seriously when I was younger. I don’t know that they take them that seriously now. 

So my lab has shifted to working on extracellular vesicles or exosomes sometimes people call them. And they have selective content of small RNA molecules and proteins and we have been studying the sorting mechanism that allows them to acquire selectively these molecules. And there’s a vast literature in this area suggesting that these extracellular vesicles target to tissues and deliver this content into the cytoplasm, which would require that the vesicle fuses at some point, either at the cell surface or once internalized it has to fuse with an endosome. And there’s no intelligence on that. Everytime I give a seminar I make challenging remarks about the lack of support for this broad conclusion that people have drawn. And of course I have become a bit of a pariah in the field because I’ve been so critical. But in fact I’m sure that the data aren’t there, and papers that have looked at this have confirmed that the uptake of these things in functional delivery of molecules into the cytoplasm is pathetic. 

So my hunch is that the way we do things, relying exclusively on cell culture, reveals that this is not a path that can be reproduced outside of an animal easily. There may be physiologic transfer events between tissues that are adjacent or particular routes that simply aren’t being reproduced in cell culture. So the challenge now that I’ve offered is for someone to demonstrate, mechanistically, how an RNA or protein molecule can be functionally delivered to the cytoplasm via an extracellular vesicle. 

LC: Nontrivial for sure. 

RS: Not at all, not at all. I hope I don’t have to retire before someone figures that out for us. 

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