This is a summer student position supervised by Marion Delphin from Philippa Matthew's lab.
Introduction to the Science
By slowly but surely inducing liver cirrhosis and/or cancer, the Hepatitis B Virus (HBV) chronic infection leads to the death of 1 million people per year. Our group works on a diverse range of approaches, ranging from molecular biology to studying clinical cohorts and population epidemiology, to provide an evidence base to support improvements in HBV diagnosis, treatment and prevention. Advances in sequencing methods have led to improved understanding of HBV genome variability, and a few studies have associated specific viral sequences with different disease outcomes, sensitivity to drugs, or even direct influence on immune cells. However, not much is known about the specific mechanisms behind these observed differences. In the lab, we are aiming to tackle these issues to better predict diverse patient outcomes and support better treatment.
About the Project
In the proposed project, the applicant will characterise an HBV variant (for example, a particular strain or genotype, or viruses that carry specific mutations). To do so, following infection in hepatocytes, they will study (1) viral parameters: HBV DNA (qPCR), RNA (RT-qPCR) and secreted viral protein HBsAg/HBeAg (ELISA) and (2) impact on hepatocyte biology, including their immune response: activation/repression of immune pathways (RT-qPCR) and secretion of messenger proteins (multiplex ELISA). By doing this, we hope to gain insight into differential replication efficiency (i.e is one variant capable of replicating more/less than the reference one?), as well as its interaction with the hepatocytes (i.e: is this variant detected by the hepatocytes? Is it activating a specific response by the cells?) and compare it to real-world observations of this variant.
About You
This project would suit a candidate studying biology, with a specific focus/interest on host-pathogen interaction, and genomics, genetics, immunology, infectious diseases, and microbiology. As the lab also works with advanced sequencing and associated bioinformatics, this area could be explored by interested applicants during their placement.
References
1. Revill, P.A., Tu, T., Netter, H.J., Yuen, L.K.W., Locarnini, S.A. and Littlejohn, M. (2020)
The evolution and clinical impact of hepatitis B virus genome diversity.
Nat Rev Gastroenterol Hepatol 17: 618-634. PubMed abstract
2. Delphin, M., Faure-Dupuy, S., Isorce, N., Rivoire, M., Salvetti, A., Durantel, D. and Lucifora, J. (2021)
Inhibitory effect of IL-1beta on HBV and HDV replication and HBs antigen-dependent modulation of its secretion by macrophages.
Viruses 14: 65. PubMed abstract
