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Antony Hewish

Astronomer

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Investigating the biology of post-traumatic stress disorder

Eric Kandel - Scientist

So that was sort of the major thing we looked… We also looked a little bit at post-traumatic stress disorder. This came out of my walking through the lab and telling people, you know, one example of a functional prion is a biological curiosity, two examples is a biological principle. Let's find another example. So Joe Rayman in my lab, who's unbelievably gifted, scoured the literature, and found that there is in many cells something called TIA, T cell intracellular antigen, that forms aggregates in cells. And these aggregates… even the person who studied it suspected they may have prion-like properties. So we put it in the yeast and we tested it rigorously and we found classic features of prion properties: forms aggregates, self-perpetuating, SDS resistant, etc. And he is beginning to explore what it does. And it turns out that it's involved in post-traumatic stress disorder. It's a protective factor, but it's a protective factor only in female mice. If you knock it out, female mice show a much more profound response to post-traumatic stress disorder. And it turns out, it seems to be a sex-specific splicing factor of the glucocorticoid receptor. So we're really trying to pin this down, and we're close to doing it. We also raised the question, there must be a male-specific splicing factor, and we're looking for that as well. Anyway. We're having a very good time with that.

Some time ago, way before the experiment with Scott Small and Gerard Karsenty we thought… actually Denise's idea…. Wally Gilbert, who's a wonderful molecular geneticist is a good friend of ours. We were having dinner together one night, and I was telling him about the early experiments with PKA and aging mice. And Denise said, there's a little red pill here, and you guys should form a company. So we've formed a company for age-related memory loss. Actually, Scott Small was on the board. And after a while we sold it to Hoffmann-La Roche. And at the time we sold it we had several drugs that were better than phosphodiesterase inhibitors that were then available, but the FDA did not accept age-related memory loss as a distinct entity. In the last year, it's changed its policy but 10 years ago when we were doing this, there was nothing like this going on. So I think Hoffmann-La Roche is in a good position now, but…

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