Interaction between host and virus in outcomes of Hepatitis B Virus infection

About the project

About the Project A 2027 Crick PhD project with Philippa Matthews. Project background and description This project will be nested in the work of the ‘Hepatitis B elimination lab’ at the Crick. The team works on a broad range of projects spanning wet lab, clinical cohorts, ‘big data’ and epidemiology to address questions that are of translational relevance to tackling the global health threat of Hepatitis B virus (HBV). We have close working collaborations with centres in Africa (including, but not limited to, South Africa, Uganda, Kenya, Ethiopia, Gambia and Ghana), recognising that HBV infection is a neglected challenge in most populations in the WHO African region. At the Crick, we have established a whole genome sequencing pipeline for HBV [1], supported by analysis tools, which are currently being scaled up, and we are working to generate host sequence data for head-to-head analysis. We have a special interest in understanding the clinical and public health significance of antiviral resistance [2]. We are also working to improve the use of biomarkers, both for risk stratification, and to help enhance an understanding of the mechanisms through which diverse outcomes of hepatitis B arise, ranging from spontaneous clearance through to severe liver disease complications of primary liver cancer (hepatocellular carcinoma) and/or cirrhosis [3]. This includes increasing our expertise in metabolic liver disease, through detailed lipidomic profiling in house at the Crick, recognising that lipids may be a significant modifier of outcomes of HBV infection and its treatment [4]. There will also be the opportunity to work with the ‘B-ZERO’ programme, a new multi-site collaboration starting in 2026, which seeks to better understand diverse treatment outcomes in people living with HBV in high prevalence settings in Africa. Specific partnerships have been established to collect data and samples in Ethiopia and South Africa, linking this to wider collaborative networks across the continent [5]. The project will focus on developing improved insights into the pathways to chronic liver disease, including host and pathogen genetics, characterisation of novel viral and human biomarkers (e.g. to measure liver reservoir, immune responses, and apply 'omics techniques), and detailed calibration of treatment both with existing standard-of-care agents (nucleos/tide analogues such as tenofovir) and expanding as the field changes to introduce novel treatments including the antisense oligonucleotide Bepirovirsen. The aim is to develop better insights into the mechanisms of adverse outcomes, allowing stratification to be applied to identify those at highest risk, and then applying evidence-based interventions to improve outcomes. The final specific focus of the project will be determined in collaboration with the successful candidate, such that the questions addressed can be tailored to suit their expertise and interests, and will be aligned with the activities of the broader group at the date of commencement of the project. The candidate will be expected to work as part of an international interdisciplinary team, and with opportunities to work in partnership with the Scientific Technology Platforms relevant to supporting specific project domains. Candidate background This project would best suit a candidate with background experience and training in infection, and with specific interests in virology, genomics, liver disease/cancer, immunology, the host/pathogen interface, and/or global health. Existing skills in data handling and analysis are desirable but not essential. Lab-specific question How does your career or experience to date inform your interest in a project on hepatitis B, and what areas of research in our lab are you most excited to advance during a PhD?

Research areas