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Sangamo's work with zinc fingers


Work on zinc fingers and mitochondria
Aaron Klug Scientist
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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.

Born in Lithuania, Aaron Klug (1926-2018) was a British chemist and biophysicist. He was awarded the Nobel Prize in Chemistry in 1982 for developments in electron microscopy and his work on complexes of nucleic acids and proteins. He studied crystallography at the University of Cape Town before moving to England, completing his doctorate in 1953 at Trinity College, Cambridge. In 1981, he was awarded the Louisa Gross Horwitz Prize from Columbia University. His long and influential career led to a knighthood in 1988. He was also elected President of the Royal Society, and served there from 1995-2000.

Listeners: Ken Holmes John Finch

Kenneth Holmes was born in London in 1934 and attended schools in Chiswick. He obtained his BA at St Johns College, Cambridge. He obtained his PhD at Birkbeck College, London working on the structure of tobacco mosaic virus with Rosalind Franklin and Aaron Klug. After a post-doc at Childrens' Hospital, Boston, where he started to work on muscle structure, he joined to the newly opened Laboratory of Molecular Biology in Cambridge where he stayed for six years. He worked with Aaron Klug on virus structure and with Hugh Huxley on muscle. He then moved to Heidelberg to open the Department of Biophysics at the Max Planck Institute for Medical Research where he remained as director until his retirement. During this time he completed the structure of tobacco mosaic virus and solved the structures of a number of protein molecules including the structure of the muscle protein actin and the actin filament. Recently he has worked on the molecular mechanism of muscle contraction. He also initiated the use of synchrotron radiation as a source for X-ray diffraction and founded the EMBL outstation at DESY Hamburg. He was elected to the Royal Society in 1981 and is a member of a number of scientific academies.

John Finch is a retired member of staff of the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. He began research as a PhD student of Rosalind Franklin's at Birkbeck College, London in 1955 studying the structure of small viruses by x-ray diffraction. He came to Cambridge as part of Aaron Klug's team in 1962 and has continued with the structural study of viruses and other nucleoproteins such as chromatin, using both x-rays and electron microscopy.

Tags: Monika Papworth

Duration: 2 minutes, 53 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008