The Matthews laboratory is a new research group at the Crick Institute that studies interactions between hepatitis B virus (HBV) and the human host in order to better understand the diverse outcomes of this infection, to characterise the burden of disease, and to inform translational insights into diagnosis, surveillance, treatment and prevention.
HBV is one of the smallest viruses to infect humans, but its biology and the mechanisms of disease remain incompletely understood, and it accounts for close to 300 million chronic cases worldwide, and a million deaths each year.
Our lab studies the interplay between host, virus and environment to better understand diverse outcomes of disease which range from spontaneous immune clearance or asymptomatic infection, through to inflammatory liver disease, cirrhosis, and hepatocellular carcinoma (HCC). A disproportionate burden of HBV disease falls upon low and middle-income countries, and we have close working partnerships with clinical research teams in South Africa and Uganda. We will also develop new partnerships with large HBV cohorts in London, providing an exciting opportunity to advance research in diverse populations represented locally.
As a group, we are setting out to address some fundamental questions about the molecular mechanisms of disease in HBV infection, with the aim of directly informing practical approaches in real-world cohorts that move us towards elimination. These include:
- What is the burden of HBV infection and liver disease in diverse populations (UK, Uganda, South Africa, and others)? How can we best measure and quantify liver disease in different settings? How are these outcomes influenced by host, viral and environmental factors (ranging from host and viral genetics, to exposure to alcohol and aflatoxin)?
- How can we refine approaches to predicting the emergence of liver disease using genomics, existing and novel laboratory biomarkers and imaging, in order to focus screening and therapy to best effect?
- How can we better deploy existing antiviral therapy to prevent disease from emerging and to reduce the risk of transmission? As new therapies emerge onto the clinical stage, where are these best directed, and how can we use molecular medicine to measure outcomes?
- How effective is vaccination in different populations, and to what extent is vaccine escape a current or future challenge?
- How can these insights into disease, its treatment, and immunisation be applied at a population level to inform preventive strategies?
To answer these questions, we will employ a diverse range of approaches, interacting with the Crick Scientific Technology Platforms (STPs). We will optimise approaches to viral sequencing, with the aim of generating HBV sequences representing infection in diverse cohorts (monoinfection and in coinfected patients), seeking viral attributes that correlate with diverse outcomes and with resistance to drugs and vaccines. Working with the structural biology STP provides an opportunity to link viral sequence to mechanistic understanding of the impact of polymorphisms. We will characterise the host immune responses using genetics and flow cytometry. We will explore multiplex approaches to measuring diverse biomarkers, correlate these with disease outcomes, and explore mechanistic relationships. Large population datasets will provide opportunities for population-level approaches to characterising disease and identification of risk factors.
You will be encouraged to participate actively in the intellectual strategy of the group, proposing hypotheses, designing approaches to relevant questions, working with existing collaborations and forging new ones, and working closely with other members of the team including providing supervision to PhD students.
For more information about current and proposed projects, please contact firstname.lastname@example.org
The Francis Crick Institute is a state-of-the-art biomedical research centre that houses a talented and engaging research community. We strive for scientific and cultural diversity that drives innovative research. For more about the Crick and why you should consider working here: https://www.youtube.com/watch?v=OeCDFbsc9So
Experience and competencies
The post holder should embody and demonstrate our core Crick values: Bold, Imaginative,
Open, Dynamic and Collegial, in addition to the following:
- PhD in Biological Sciences (or in final stages)
- Evidence of independent and original contribution to research
- Ability to manage project timelines
- Ability to work collaboratively in small groups, and to join a team of local, national and international partners
- Ability to communicate and present data at meetings and conferences
- Expertise in one or more of the following is highly desirable: bioinformatics, host and/or pathogen sequencing, viral biology/immunology