Molecular Mechanisms of Chronic Hepatitis B Persistence
A collaborative approach
Hepatitis B virus (HBV) is a major health problem with >240 million cases worldwide and >780,000 deaths/year from liver diseases including cirrhosis and hepatocellular carcinoma (HCC). Available treatments suppress viral replication but are not curative. In most cases treatment is life-long with patients at risk of developing HCC. There is a global initiative to develop curative therapies, however progress has been limited by two major roadblocks: persistence of the HBV covalently closed circular DNA (cccDNA) and inadequate host immune responses. In this project, scientists will use a range of experimental approaches to uncover the mechanisms underlying these roadblocks and allow the discovery of new therapeutic targets.
Along with our collaborators in the Issa lab (https://www.nds.ox.ac.uk/team/fadi-issa ) and the McKeating Lab (https://www.ndm.ox.ac.uk/team/jane-mckeating ) we are seeking to recruit a team of dedicated researchers (see vacancies below) to:
- Better understand how HBV cccDNA transcriptional activity varies across the liver
- Discover the mechanisms of cellular resistance to HBV in chronic disease
- Define the role of hypoxia in hepatocyte susceptibility to HBV and liver resident immunity in chronic disease.
Post in the Davis Lab
A 5-year postdoctoral research position in the Davis Lab is now open to applications to work on this project. The position combines computational methods with cutting-edge imaging and spatial transcriptomics. For informal enquiries contact darragh.ennis@bioch.ox.ac.uk , or to apply click below.
Vacancies on the Project
Bioinformatician
Cellular Immunologist
Bioinformatician
An experienced bioinformatician post that will focus on analysis of complex smFISH data and combine it with digital spatial profiling data.
Microscopist
Cellular Immunologist
Bioinformatician
A skilled microscopist is sought to undertake the single-molecule imaging and spatial transcriptomics aspects of the project.
Cellular Immunologist
Cellular Immunologist
Cellular Immunologist
A researcher with experience of in situ multiplex tissue staining, imaging and data analysis.
Relevant Publications
Wing PAC, Liu PJ, Harris JM, Magri A, Michler T, Zhuang X, Borrmann H, Minisini R, Frampton NR, Wettengel JM, Mailly L, D'Arienzo V, Riedl T, Nobre L, Weekes MP, Pirisi M, Heikenwalder M, Baumert TF, Hammond EM, Mole DR, Protzer U, Balfe P, McKeating JA. Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter. J Hepatol. 2021 Jul;75(1):64-73. doi: 10.1016/j.jhep.2020.12.034. Epub 2021 Jan 29. PMID: 33516779; PMCID: PMC8214165.
Zhang X, Lu W, Zheng Y, Wang W, Bai L, Chen L, Feng Y, Zhang Z, Yuan Z. In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection. J Clin Invest. 2016 Mar 1;126(3):1079-92. doi: 10.1172/JCI83339. Epub 2016 Feb 22. PMID: 26901811; PMCID: PMC4767362.
Lee JY, Wing PAC, Gala DS, Noerenberg M, Järvelin AI, Titlow J, Zhuang X, Palmalux N, Iselin L, Thompson MK, Parton RM, Prange-Barczynska M, Wainman A, Salguero FJ, Bishop T, Agranoff D, James W, Castello A, McKeating JA, Davis I. Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences. Elife. 2022 Jan 20;11:e74153. doi: 10.7554/eLife.74153. PMID: 35049501; PMCID: PMC8776252.