Mechanisms of Epstein-Barr virus-driven cellular reprogramming and transformation
The research in our laboratory is focussed on deciphering the mechanisms involved in B-cell transformation by the cancer-associated herpesvirus, Epstein-Barr virus (EBV).
EBV is associated with the pathogenesis of numerous lymphoid tumours including Burkitt’s lymphoma, Hodgkin’s disease, post-transplant lymphoma and certain T-cell and natural killer cell lymphomas, in addition to the epithelial-cell tumour nasopharyngeal carcinoma. The oncogenic properties of the virus are reflected by its ability to immortalise resting B-cells in vitro generating permanently proliferating lymphoblastoid cell-lines (LCLs). Like other members of the herpesvirus family, EBV has a biphasic life cycle involving a latent and lytic phase. In infected B-cells EBV establishes a latent infection where the 172 kb double-stranded DNA viral genome is maintained as a closed circular episome and expresses a limited set of latent gene products. These include the Epstein-Barr nuclear antigens (EBNAs) 1, 2, 3A, 3B, 3C, LP and latent membrane proteins (LMPs) 1, 2A and 2B, the untranslated Epstein-Barr-encoded RNAs EBER 1 and EBER 2 and numerous microRNAs. EBNA 1, 2, 3A, 3C and LMP1 play essential roles in B-cell infection and immortalisation since loss of each of these genes renders viruses incapable of establishing permanently proliferating LCLs in vitro.
Despite its cancer-promoting properties, effective immune control combined with restricted expression of only subsets of latent proteins during viral persistence in vivo, enables over 95% of the world’s population to carry EBV as a lifelong asymptomatic infection. EBV infection via the exchange of saliva usually passses unnoticed in early childhood, but if delayed until early adulthood, primary infection can result in the benign lymphoproliferative disease, infectious mononucelosis (glandular fever).
All of the EBNAs function as transcriptional regulators and a key aspect of our research aims to define the molecular mechanisms involved in the regulation of viral and cellular gene transcription by EBV-encoded factors, with a specific focus on the EBNA 2 and 3C proteins. We are particularly interested in the regulation of transcription elongation, RNA polymerase II pausing and the role of EBV-encoded factors in reprogramming B-cell transcription and gene expression in transformed cells.
We welcome enquiries from self-funding PhD students and other researchers interested in joining our laboratory. Please e-mail Dr Michelle West with your CV and details of your research interests.
We have a vacancy for a post-doctoral research scientist in the West group available from September 2013:
Post-doctoral research position details
We are very grateful to have received funding from the following organisations to support our research:
