How cells detect and control hepatitis B virus

Project Overview

Project Overview

Virus infection triggers a multitude of immune responses. Detection of virus presence by the innate immune system is a crucial event and is mediated by receptors inside cells. These viral sensors activate innate immune genes, such as those encoding type I interferons. These cytokines then alert neighbouring, uninfected cells and induce the expression of hundreds of genes, many of which encode proteins with direct anti-viral properties. Viruses in turn have developed strategies to counteract and evade detection of the host innate immune system. As such, cells and viruses are in a dynamic arms race in which host defence mechanisms and viral counter-measures co-evolve. Our aim is to understand the molecular basis of host pathogen interactions.

This project will address these questions in the context of hepatitis B virus (HBV), which is a major public health concern. HBV can establish a chronic infection that is associated with progressive liver disease and the development of liver cancer. Little is known about innate immune responses to HBV. Our unpublished observations suggest that HBV infection is controlled by SAMHD1, a cellular protein induced by interferons. Interestingly, SAMHD1 impacts on multiple stages in the HBV life cycle.

The successful candidate will extend these studies by investigating the molecular mechanisms underlying these observations. In particular, we will (i) identify the molecular mechanisms by which SAMHD1 restricts HBV replication, (ii) investigate how HBV counteracts SAMHD1 and (iii) analyse how these host-virus interactions are shaped by the tissue microenvironment. The project has basic and translational research components. Taken together, this exciting project builds on strong preliminary results and will increase our understanding of host immune responses to HBV. 

Training Opportunities

The successful candidate will be based in the NMD Research Building in Prof. McKeatings group, with close interactions with Dr. Rehwinkel’s lab in the MRC Human Immunology Unit at the Weatherall Institute of Molecular Medicine. We offer access to state-of-the-art facilities and provide an opportunity for training in a broad range of different techniques, including cell culture, molecular biology, immunology and virology. This project will additionally benefit from close collaboration with many scientists. The successful candidate will be co-supervised by Jane McKeating and Jan Rehwinkel and additional day-to-day supervision will be provided by experienced members of both labs.

Theme

Immunology & Infectious Disease

Admissions

Project reference number: 986

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
Prof Jan Rehwinkel Investigative Medicine Division Oxford University, Weatherall Institute of Molecular Medicine GBR jan.rehwinkel@imm.ox.ac.uk

There are no publications listed for this DPhil project.