PhD Studentship: Structural and functional studies of replication and transcription of emerging bunyavirus and hantaan viruses



Deadline: 19 January 2014.

Start Date: 1 April 2014.

Supervisory Team: Primary Supervisor: Professor Changjiang Dong, Email: c.dong@uea.ac.uk
Secondary Supervisor: Dr. Kevin Tyler , Email: k.tyler@uea.ac.uk

The Project:

Bunyaviridae is a large family of negative stranded viruses, which contains more than 350 members. Many of them are significant human pathogens, causing thousands of deaths annually. Particularly, the hantaan viruses are widely spread in the world, resulting severe human diseases. There are no effective vaccine and drugs available. The bunyaviruses have tripartitle genomes that consist of a large (L), medium (M) and small (S) RNA segments, encoding glycoproteins, RNA-dependent RNA polymerase L, nucleoprotein and non-structural proteins. The nucleoprotein and the RNA-dependent RNA polymerase play essential roles in the viral RNA transcription and replication, but the mechanisms are unclear. The knowledge of the viral replication and the transcription are important for controlling these viral infections.   

To understand the transcription and replication in molecular level, this exciting project is going to express and purify both L protein and NP protein, and reconstitute the replication machinery in vitro for activity assays, and determine the crystal structures of the replication complex.

The RNA-dependant polymerase L and nucleoprotein will be over-expressed in insect or E.coli expression systems, and the proteins will be purified. The purified proteins will be constituted as RNA replication complexes in vitro, and the replication and transcription activities be tested in vitro. The two proteins will be crystallized, and the structures will be determined. To find out the RNA replication and transcription molecular mechanisms, mutagenesis will be carried and the functions of the mutants will be investigated. Based on the structures, rational structure-based drug designs will be carried out.

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This studentship provides excellent training opportunity in the emerging areas in microbiology, molecular biology, virology, immunity, structural biology, chemical biology and rational drug development, particularly in gene manipulations, protein expression in different systems, protein and protein or protein and small molecules interaction, structure determination using both X-ray crystallography and NMR, rational drug design. It involves collaborations across the Norwich Research Park, which has more than 2,700 scientists and performs world-leading research in microbiology.

Entry Requirements:

Applicants should hold a 2:1 degree or above in Biology, Biochemistry, Microbiology, medicine and chemistry 

Those applicants whose first language is not English must demonstrate evidence of appropriate English language proficiency, normally defined as a minimum IELTS score of 6.5 (Overall Band Score) with 6.0 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 via the ‘Apply’ button below.

To discuss the application process, please contact the: Admissions Office, email: pgr.enquiries.admiss@uea.ac.uk or telephone +44 (0)1603 591709.

To discuss the specific project and arrange an informal visit, please contact the primary or secondary supervisors via their email.

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