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ADAMTS13 structure in normal and disease states

  • Full or part time
  • Application Deadline
    Friday, January 17, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

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. To understand this 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 purpura.

Funding Notes

The studentships will commence in October 2020, and a stipend (£15,009 for 2019/20) and fee waiver for 3.5 years is available for UK applicants, plus research training support grant, travel and laptop allowance.

Fully funded studentships are available for UK applicants. EU applicants able to confirm that they have been resident in the UK for at least three years before October 2020 may also be eligible for a full award. EU students who are not able to prove that they meet the residency criteria may apply for a fees only award.

Interviews take place week commencing 17 February 2020.

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