MRC National Institute for Medical Research, London
Science for Health
NIMR research featured in MRC Annual Review 2008-9
06 August 2009
The MRC Annual Review 08/09 is titled "A day of discovery" and provides a glimpse into a day in the life of the MRC, dropping in on MRC people over the course of their working day to find out what they’re doing. It also highlights some of the MRC's broad-ranging scientific achievements. It includes a profile of Alex Gould, in NIMR's Division of Developmental Neurobiology and highlights four other NIMR research groups.
Robin Lovell-Badge
By studying genetic events in mice Robin Lovell-Badge and colleagues have discovered that the protein encoded by Sry enhances the activity of Sox9. It does this with the help of another protein, SF1, which is present in cells of both sexes but can’t trigger male development by itself. The interaction between Sry and SF1 amplifies the effect of Sox9 so that it can then promote the activity of more genes responsible for other testes-creating cells. (Page 13 of the Annual Review - How genes talk to each other to determine sex).
Chrisantha Fernando
Chrisantha Fernando, in Richard Goldstein's research group, has applied the mathematical model of Pavlov-type associative learning in neurons to molecular circuits, and found they had the potential to be used in single-celled organisms such as bacteria. Associative learning was previously thought to be confined to animals with nervous systems but scientists have now realised there is a strong possibility that it can be applied to molecular circuits. The scientists think that implanting a molecular circuit in bacteria inhabiting a patient could adapt to learn the anticipatory release of a drug which was particular to that patient’s needs. (Page 14 of the Annual Review - From Pavlov’s dogs to smart bacteria).
Alex Gould
Alex Gould 's team have identified genes in Drosophila that control how large the developing brain becomes. Within the growing brain, stem cells divide to produce more and more neurons until an upper limit is reached. The scientists found that two ‘timer’ genes – named Castor and Seven-up – tell stem cells when and how to stop dividing, thus preventing the brain from growing too large. (Page 36 of the Annual Review - Timer genes control brain size. Profile of Alex Gould on page 35).
François Guillemot
François Guillemot's research in mouse embryos has identified two genes that help to coordinate the structure of the brain. Brain neurons (nerve cells) are always generated at a distance from their final location and so they have to travel along specific routes for the brain to be put together correctly. When the scientists stopped expression of Rnd2 gene in developing mouse neurons, the cells got ‘lost’ and could not follow the usual route to the cerebral cortex. In contrast brain cells that were not blocked switched on Rnd2 just before migration began. Further work showed that the product of a second gene, Neurogenin2, prompts expression of Rnd2 and in doing so coordinates development of the cerebral cortex. (Page 38 of the Annual Review - Simple genetic path creates brain architecture)
Steve Gamblin
Steve Gamblin uncovered a change in the H5N1 bird flu virus, which makes it resistant to the anti-viral drug oseltamivir (Tamiflu™). The research looked at the structure of the flu virus neuraminidase (N1) which is the target for Tamiflu™ and the other existing flu drug, zanamivir (Relenza™). Both drugs aim to inhibit the N1 which is responsible for releasing the virus from infected human cells and thus allowing the disease to spread. Using X-ray crystallography the scientists looked at a mutation in the structure of N1 that has been found in human cases of H5N1 and in seasonal flu. They discovered that when this mutation occurred, the virus became resistant to Tamiflu™, while still remaining susceptible to Relenza™. (Page 50 of the Annual Review - More drugs needed to fight flu pandemics).
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