Fully Funded Studentship: Structural and functional studies of viral RNA replication and transcription machineries of Lassa fever and other emerging viruses and drug design



Faculty of Medicine and Health Sciences

Application Deadline: 30th June 2013

Start Date: 1st October  2013

Supervisory Team:

Primary: Professor Changjiang Dong  

Secondary: Professor Tom Wileman

The Project:

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 people’s lives not only in Africa, but also in Europe, America and Asia. 

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.  The project will entail i)  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) Characterizing  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.

Also Read  Fully-funded MSc by Research Scholarship: Development of novel anti-reflective coating & wafer splitting technologies

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.

Entry Requirements:

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.

Funding:

Full Funding is available for Home/EU students, covering fees and an annual stipend of £13,726 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 University’s online application system. 

To discuss the application process or particular projects, please contact the: Admissions Office, email: [email protected] or telephone +44 (0)1603 591709.

Leave a Reply

Your email address will not be published. Required fields are marked *