Employing molecular virology to investigate hepatitis E virus replication

Supervisor(s)

Dr Morgan Herod

Prof. Mark Harris

Project description

Hepatitis E virus (HEV), is a major causative agent of acute, severe hepatitis. The infection can also be chronic, particular in immunocompromised people, and fatal in pregnant women or those with existing liver diseases. The virus is zoonotic (i.e. it can spread from animals to humans) and can infect a wide range of organisms, most notable pigs where it can be passed onto humans through consumption of contaminated pork products. There are no licenced therapies to treat HEV infection and therefore there is a requirement to develop new therapeutic strategies. Until recently, probing details of HEV replication has been challenging, partly due to the lack of suitable reagents. This project aims to exploit recent developments of subgenomic replicon systems and infectious molecular clones to identify and characterise regions of the genome required for viral genome replication.

Subgenomic replicons are viral mini-genomes that facilitate the study of fundamental mechanisms of viral genome replication in the absence of infectious virus and have been established for many RNA viruses. Using random mutagenesis with HEV subgenomic replicons we will dissect regions of the viral genome that are essential for replication as well as locations that are malleable for introduction of genetic tags (eg FLAG, GFP). This approach will pave the way for studies on viral molecular interaction and identify novel roles of the essential non-structural proteins and their precursors (together with biochemistry, labelling techniques and state-of-the-art imaging facilities).

The long-term aim of the work is to use a greater knowledge of the molecular details of viral replication to develop new approaches for disease control and diagnosis.

Entry requirements

Candidates should have, or be expecting, a 2.1 hons at Undergraduate level or above, in a relevant subject. If English is not your first language, you will need a recognised English Language qualification to be admitted onto any of the University's degree programmes: https://www.leeds.ac.uk/info/123100/admissions/143/entry_requirements

How to apply

Please apply online

Select “PhD in Biological Sciences” as the proposed course

Please include supervisor name and project title.  A research proposal is not required.  Please upload a CV and transcripts.

How to apply (email)

fbsgrad@leeds.ac.uk

How to apply (phone)

+44 (0)113 343 8186