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PhD studentship available
ADAMTS13 stucture in normal and disease states We are seeking to appoint a highly motivated student to undertake a joint PhD at the University of Nottingham, under the supervision of Prof Jonas Emsley, Dr Neil Morgan (University of Birmingham) and Prof John Schwabe (University of Leicester). The successful candidate will spend time at all three Universities. https://more.bham.ac.uk/mrc-impact/phd-opportunities/. https://www.nottingham.ac.uk/jobs/currentvacancies/cat/213
Blood clotting requires recruitment of platelets (specialised blood cells) to the site of injury as one of the first (of many) events that prevents bleeding. This process is highly dependent upon a protein known as von Willebrand factor (VWF) that circulates in blood which is regulated by ADAMTS13 (A Disintegrin-like And Metalloprotease with ThromboSpondin type I repeats, member 13). Clinically, human deficiency in VWF is the most common inherited bleeding disorder, whereas people with ADAMTS13 deficiency suffer from a life-threatening thrombotic disorder with a ~90% mortality rate. ADAMTS13 is a very highly specific proteolytic enzyme that cleaves only one protein (VWF) and does so at just a single site, and even then, only under very specific conditions of blood flow. The metalloprotease domain of this enzyme contains the active site that cleaves VWF and how ADAMTS13 recognises and cleaves VWF so specifically remains unclear. We recently determine the crystal structure of the N-terminal domains in collaboration with Imperial College1. To understand regulation at a molecular level, we will ascertain the structure of whole ADAMTS13, both in free forms and in stabilising complexes with specific antibody fragments using cryo-electron microscopy. We will also analyse hereditary mutations in the ADAMTS13 gene linked to paediatric stroke and thrombotic thrombocytopenic purpura2.
references: 1. Nature Commun 10, 3781. Petri, A., Kim, H. J., Xu, Y., de Groot, R., Li, C., Vandenbulcke, A., Vanhoorelbeke, K., Emsley, J., and Crawley, J. T. B. (2019) Crystal structure and substrate-induced activation of ADAMTS13. 2.Nature. 2001;413(6855):488-94. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Levy GG1, et al Ginsburg D, Tsai HM
MRC IMPACT Doctoral Training Partnership Closing date: Friday, 17 January 2020 Schools: Life Sciences, Medicine, Physics and Astronomy, Pharmacy, Psychology, Veterinary Medicine and Science Applications are now open for a range of exciting projects to study Complex Disease for a September 2020 start. Interviews will take place the week commencing 17 February 2020. Application details are on the MRC IMPACT DTP website.
In addition, I have put the adverts on FindAPhD (apart from a couple, which were already up). If you search on UoN and then Graduate Schoolhttps://www.findaphd.com/phds/graduate-school/?c0wkxd80 you
should be able to find your project.
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Dr Jonas Emsley
Professor of Macromolecular Crystallography,
Centre for Biomolecular Sciences,
School of Pharmacy,
University of Nottingham,
University Park,
Nottingham.
NG72RD
Tel: +44 1158467092
Fax: +44 1158468002
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