Xiaolin Nan, is an assistant professor at Oregon Health and Science University. Until recently, he worked in Dr. Steven Chu’s lab doing imaging of single molecules. His background is physical chemistry and after that he trained as a biophysicist , concentrating on cancer biology.
Xiaolin Nan: Okay, so my research is a little bit different from most of the other PS-OC investigators, in that I'm looking at a very small length scale. The length scale of about a single protein or single protein complex and we all know that understanding how proteins come together inside a cell is extremely important to understanding how the cell actually carries out certain functions and sometimes gets deregulated and becomes a tumor. So, what we want to do is to use new technologies that enable us to map out individual proteins on the scale of a few nanometers to 10 nm inside a cell. That allows us to visualize how things come together on that scale and become functional complexes.
Pauline Davies: It sounds like very challenging work. What are some of the difficulties?
Xiaolin Nan: So the difficulty lies in two parts. First, is the that the technique was fairly new when we started the investigation. So there is a lot of tweaking and optimization of the imaging conditions to make it work for the purpose. The second part is of course, I was trained as a physicist so and this type of research requires that I start to learn a lot of the biology tricks: molecular cloning, the establishing cell lines, biochemical assays to verify that I got the right stuff. So making the perfect biological sample is the second challenge especially a challenge to a physicist.
Pauline Davies: And what are you finding?
Xiaolin Nan: So what we're finding is quite surprising to us. You know, some of the molecules specifically, Ras and Raf, these proteins traditionally were thought to act alone and regardless of how they are packed on cell membrane in the cytoplasm they always act the same way. But what we're finding is that spatial arrangement of these molecules actually have a strong impact on their biological activity. For example, Raf, the kinase that was implicated in melanoma and a few other types of cancers, actually needs to form dimers in order to activate the downstream signaling cascade. There's also some other interesting findings on the other protein, the upstream Ras protein in that they also need to organize into certain structures in order to activate Raf and some other downstream signaling factors.
Pauline Davies: And you only see these structures in abnormal arrangements in proteins?
Xiaolin Nan: That's right. These special arrangements are strongly connected with their oncogenetic potential.
Pauline Davies: So as far as the next step, and what can be done, can you find any way of disrupting how these proteins come together in this peculiar way?
Xiaolin Nan: That's a very good question. That's the exactly one of the directions we’re pursuing. So finding this new mechanisms of how this molecule is working inside the cell provides us with a new handle to target this molecule by a finding ways to disrupt this aspect of their signaling activity rate. For example, if Raf, the kinase needs to be a dimer then you want to design small molecules to inhibit their activity without inducing their dimers, or some other molecules might prevent them from forming dimers at all and that could potentially be useful for targeted cancer therapy.
Pauline Davies: You have a couple of papers coming out and I think you have some special results; can you tell me anything about those?
Xiaolin Nan: Oh publication wise, so we have one paper that was just reviewed forPNA. And there is some good feedback. So the paper likely is going to be accepted and so we’re hopeful that it will come out sometime this year. And there is another paper down the road about the signaling mechanisms on wrasse and were putting it together.
Pauline Davies: You’re talking tomorrow here at this conference, what are you going to be saying?
Xiaolin Nan: I'll be reporting the findings that I just told you mostly. So it really what brought us to the new findings is both by pushing the forefront of the technology, and also by identifying some of the most demanding biological questions. So what we’re doing in my lab right now is exactly both. So were continuing to work on Ras-Raf signaling, but on the other hand we’re also trying to push the technology too; for example, being able to look at more molecular species at the same time so that you can look at more complex problems. And the other advances we are making is try to push the resolution even higher so that we can have even sharper images of was happening inside the cell.
Pauline Davies: Thank you very much.
Xiaolin Nan: Thank you.