Faculty of Medicine and Health Sciences
Application Deadline: 30th June 2013
Start Date: 1st OctoberÂ 2013
Primary:Â Professor Changjiang DongÂ Â
Secondary: Professor Tom Wileman
Arenaviruses have more than 27 members and at least six of them cause severe viral haemorrhagic fevers. Lassa fever virus is the deadest arenavirus, and Lassa fever is one of the most neglected tropic diseases in Africa, infecting hundreds and thousands of people and causing more than 5,000 deaths every year. As there is no vaccine and effective drug available, Lassa fever virus is threating peopleâs lives not only in Africa, but also in Europe, America and Asia.Â
To understand the viral biological processes is essential for developing vaccines and drugs. This project will follow our recent publication (Nature, 468(7325):779-83) and find out the novel mechanisms of how the nucleoprotein of Lassa fever virus involves in immune suppression, viral RNA replication and transcription. During this exciting project, we will use the approaches of virology, biochemistry, biophysics, structural biology and cell biology to test our hypotheses, which will help us to develop new therapies.
The lab is well equipped with state-of-the art facilities for protein production, protein purification, macromolecular crystallization, molecular biology, biophysics and cell biology.Â The project will entail i)Â cloning the viral RNA polymerase and domains to E. coli or insect cell expression plasmids, ii) Over-expressing and purifing the viral RNA-polymerase protein or domains by affinity and gel filtration columns, iii) CharacterizingÂ the purified proteins, set up in vitro assays. To determine the L-polymerase and nucleoprotein interaction, the L-polymerase., iv) Crystallizing the viral polymerase or domains and determine the crystal structures of the polymerase and domains v) Mutagenesis and cell-based mini-replicon assays to confirm the structural findings, and vi) Structure-based drug design.
Qi X, Lan S, Wang W, Schelde LM, Dong H, Wallat GD, Ly H, Liang Y, Dong C. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature. 2010 Dec 9;468(7325):779-83.
Jiang X, Huang Q, Wang W, Dong H, Ly H, Liang Y, Dong C. Structures of arenaviral nucleoproteins with triphosphate dsRNA reveal a unique mechanism of immune suppression. J Biol Chem. 2013 Apr 24. [Epub ahead of print]
Dong H, Li P, Elliott R, Dong C. Structure of Schmallenberg orthobunyavirus nucleoprotein suggests a novel mechanism for genome encapsidation. Journal of virol. 2013; 87(10):5593-601.
Applicants should hold a first degree (2.1 or higher) or a master’s degree in biological sciences, chemistry or medicine.
Those applicants whose first language is not English must demonstrate evidence of appropriate English language proficiency, normally defined as a minimum IELTS score of 7.5 (Overall Band Score) with 7.0 in all elements or equivalent.
Full Funding is available for Home/EU students, covering fees and an annual stipend of Â£13,726Â for three years. Due to funding restrictions applications are also accepted from non-EU applicants who are able to pay the difference in international fees.
Making Your Application:
Please apply via the Universityâs online application system.Â
To discuss the application process or particular projects, please contact the: Admissions Office, email: [email protected] or telephone +44 (0)1603 591709.