Michel Strubin Group
Department of Microbiology and Molecular Medicine - Faculty of Medicine, University of Geneva
Project at a glance
Our research focuses on two main objectives.
- Taking advantage of the technology available in the yeast Saccharomyces cerevisiae to address fundamental questions about the mechanisms by which eukaryotic gene transcription is regulated.
- Understanding the mechanisms by which the HBx protein of hepatitis B virus contributes to viral infection and the pathogenesis of liver cancer.
Regulation of gene expression in eukaryotes
The regulation of gene expression is a fundamental aspect of most biological processes.
Our past and ongoing work aims at using yeast as a model system to explore the molecular mechanisms whereby genes are transcribed in a controlled fashion.
We are particularly interested in understanding how the basal transcription machinery, a large complex that contains many proteins in addition to the RNA polymerase, assembles at the promoter of genes and how this event is regulated.
More recently, we became interested in studying the dynamics and epigenetic modifications of nucleosomes, the structural unit of chromatin, that are associated with transcriptional activity.
The HBx protein of hepatitis B virus
Chronic infection by hepatitis B virus (HBV) is a leading cause of liver cancer.
HBV encodes a small protein, known as HBx, which is essential for viral infection and has been implicated in HBV-associated liver cancer.
The basis for HBx function in either process remains elusive and is the focus of our studies.
We obtained strong evidence that HBx promotes viral gene expression by an unusual mechanism that affects only extrachromosomal DNA templates and that requires HBx to function as a substrate receptor for a cellular E3 ubiquitin ligase complex.
We now aim to identify the substrate(s) recruited by HBx to the E3 ligase and further explore the mechanisms whereby HBx promotes viral gene expression under experimental conditions closer to natural HBV infection.
Because of its uncommon property and key role in viral transcription, HBx represents an attractive target for new antiviral therapies.