Regulation of Hepatitis B Virus Infection by Hypoxic Signalling Pathways.

Project Overview

Hypoxia Inducible Factors (HIFs)

Viruses are obligate parasites that have evolved to manipulate their host to their advantage. Chronic viral infection of the liver is a global health problem, with over 270 million individuals infected with hepatitis B (HBV) virus that causes liver disease which can progress to liver cancer. HBV is the number 8 killer worldwide and is associated with 800,000 deaths/year with limited therapies, highlighting an urgent need for new curative treatments.

We recently discovered that low oxygen environments, naturally found in the liver, enhance HBV replication at several steps in the viral life cycle. Cellular response to low oxygen is regulated by a family of oxygenases and hypoxia inducible factors (HIFs) that control genes involved in energy metabolism and other cellular processes. This project will study the role of hypoxic signalling and other related pathways in HBV replication and their impact on immune based and epigenetic therapies.

The successful candidate will investigate the molecular mechanisms underlying these observations. In particular, we will (i) identify the role of HIFs in HBV cccDNA biogenesis, transcription and metabolism, and production of infectious particles; (ii) analyse how these host-virus interactions are shaped by the tissue microenvironment, genetic manipulations and metabolic parameters. The project has basic and translational research components and applies state-of-the-art technologies, tools and model systems to study HBV infection and its mechanism of disease. Taken together, this exciting project builds on strong preliminary results and existing expertise that may lead to new therapeutic targets and antiviral development.

Training Opportunities

The successful candidate will work with Profs Jane McKeating (OXF) and T. Jake Liang (NIH). We offer access to state-of-the-art facilities and provide an opportunity for training in a broad range of different techniques including HBV virology, hypoxia biology, stem cell culture and various omic technologies. The candidate will work in a highly collaborative environment in both laboratories, and will have ample opportunities to interact with many scientists in the larger Oxford and NIH communities.

Theme

Immunology & Infectious Disease

Admissions

Project reference number: 997

Funding and admissions information

Supervisors

Name Department Institution Country Email
Professor Jane McKeating NDM Research Building Oxford University, NDM Research Building GBR jane.mckeating@ndm.ox.ac.uk
Professor Jake Liang Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases USA jakel@mail.nih.gov

There are no publications listed for this DPhil project.