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[ccp4bb] PhD Studentship in Structural Biology of Metalloproteins |
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CCP4bb navigationCCP4bb <-- 2008 <-- May 2008 <-- 13 May 2008Subject: PhD Studentship in Structural Biology of Metalloproteins From: "Hough, MA (Michael)" m {- dot -} a {- dot -} hough {- at -} DL {- dot -} AC {- dot -} UK Date: 2008-05-13 Ph.D. in Structural Biology of Metalloproteins Project: Structure based insights and interventions into SOD1-related motor neuron disease Stipend: £13,000 per annum More than 100 mutations of Cu-Zn superoxide dismutase (SOD1) are associated with the familial form of amyotrophic lateral sclerosis (ALS), a disorder affecting the integrity of motor neurons in the brain and spinal cord and leading to paralysis and death, usually within 5 years. While health care providers can do a great deal to ease the discomfort and anxiety experienced by ALS patients, there is no known cure. The SOD1-linked sub-set of the disease offers the best chance of understanding its origin and arriving at a general strategy for a cure. Current research strongly suggests that the gain of a toxic property by this otherwise essential enzyme is the cause of its pathogenic properties. We are pursuing an intensive program that involves both computational and experimental approaches based on structural data. Our main objective is to reveal the common structural factors that make the mutations of the SOD1 molecule so lethal compared to the wild-type enzyme, with the aim of stabilising the structures of pathogenic variants via a structure based lead optimisation programme. The Ph.D. studentship is jointly funded by the University and a small US biotech company. The successful candidate will use a multidisciplinary approach based on X-ray crystallography, Xray scattering and molecular biology methods. The project will be important for the future development of therapeutic remedies for the familial form of the disease and will have wider implications for the more common sporadic motor neuron disease as well as possibly other neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We are looking for candidates with strong motivation and interest in applying biophysical methods to important biological problems. A background in molecular biology or biochemistry is desirable. Funding Notes Review of applications will begin immediately till a suitable candidate is found. You will need to be a citizen of the European Union. Funding is available for an immediate start. MBG web page: www.biophysics.dl.ac.uk Elam JS, Taylor AB, Strange R, Antonyuk S, Doucette PA, Rodriguez JA, Hasnain SS, Hayward LJ, Valentine JS, Yeates TO, et al.: Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS. Nature Struct. Biol. 2003, 10:461-467. Hough MA, Grossman JG, Antonyuk SV, Strange RW, Doucette PA, Roderiguez J, Whitson LJ, Hart P, Haywood LJ, Valentine JS, et al.: Destabilisation of the Dimer Interface in SOD1 may result in disease causing properties: Structures of motor neuron disease mutants A4V and I113T. Proc. Natl. Acad. Sci. USA 2004, 101:5976-5981. Strange RW, Antonyuk S, Hough MA, Doucette PA, Valentine JS, Hasnain SS: Variable metallation of human superoxide dismutase: atomic and high-resolution crystal structures of Cu-Zn, Zn-Zn and 'as isolated' wild-type enzymes. J. Mol. Biol. 2006, 356:1152-1162. Strange RW, Yong C, Smith WL, Hasnain SS: Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase. Proc. Natl. Acad. Sci. USA 2007, 104:10040-10044. For informal inquiries please contact Dr. Richard Strange (01925 603658; email: r.w.strange@liverpool.ac.uk) or Prof. S. Samar Hasnain (01925 603273; email: s.s.hasnain@liverpool.ac.uk). CCP4bb navigationCCP4bb <-- 2008 <-- May 2008 <-- 13 May 2008 |
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