All these people dispersed, one of them became a patent agent, that's Michael Moore, others, Yen Choo went on to do other things, he's now got another company, Mark Isalan went off to the EMBL and so on but I still have a small group, I'm still a group leader here. At least for a limited time. And I decided that what we would do was to try to... target zinc fingers into mitochondria because mitochondria are a sort of black box, and of course they do replicate and they do produce proteins, but most of the proteins in mitochondria are coded in the nucleus and they get transferred, transported into the mitochondria and there are carrier signals... amino acid sequences in front of the mitochondrial protein which act like an entry ticket into the mitochondria and these get cleaved off. The reasons this was sort of adventitious, the reason I chose this is because I wanted to do something that nobody else was doing, as I've said before there's so many people working on zinc fingers and zinc carriers in the obvious places, but it turned out to be not so easy. One of the advantages we had a... I have a Polish... originally Polish, married to an Englishman, a woman post doc, Monika Papworth who comes from a lab, originally a lab in Poland where they work on mitochondria. So we had a visitor from the lab who came to learn zinc finger technology and he introduced us to mitochondrial technology. And there's also a study of mitochondria going on in the MRC nutrition unit and I thought that would be quite useful because they are trying to understand various aspects of gene regulation... very little... it's really pure science. Well, it's pure science but one might be able to switch off genes in what's called heteroplasmy. It turns out that many diseases, mitochondrial diseases, of which there are many, are rather strange. Some mitochondria have a mutation and these are deleterious mutations and of course they inherit it in the next generation. At the same time, it's a mixed population, there are other perfectly healthy mitochondria so one or two diseases of mitochondria you could, you probably could if you could knock out a simple, knock out those mitochondria which have the deleterious gene then you could cure the disease. Of course, as I have said, I was interested in applying these things to real cases.
