The Roslin Institute
Functional analysis of viral microRNAs.
The recent discovery of a new class of regulatory genes known as microRNAs (miRNAs) has resulted in a paradigm shift in gene regulation research. miRNAs are small single-stranded RNA species of approximately 20-24 bases in length that regulate gene expression through post transcriptional mechanisms. miRNAs are thought to be ubiquitously expressed by plants and animals and play integral roles in diverse biological processes including host pathogen interactions. To date more than 100 viral miRNAs have been identified, almost all of which are expressed by herpesviruses. The focus of my research is to determine the role of microRNAs in host pathogen interactions and, in particular, the role of herpesvirus encoded miRNAs during viral infection.
Our current research has focused on Human cytomegalovirus (HCMV). HCMV is an enveloped, double-stranded DNA virus that establishes a systemic persistent infection of the host. Although in the majority of cases infections are asymptomatic, HCMV can cause a number of diseases including birth abnormalities, vascular diseases and significant morbidity in immunocompromised individuals. Like all herpesviruses, HCMV has the ability to maintain life long persistent infections, resulting in infection rates as high as 100% of the population. In order to persist in the host, herpesviruses establish a latent infection characterized by severe restriction of viral gene expression and production of infectious virus, allowing the virus to “hide” from the host immune response.
HCMV encodes at least 11 miRNA genes. The use of cutting edge technologies such as RISC immunoprecipitation and the ability to rapidly manipulate viral genomes through BAC technology has allowed us to identify numerous cellular and viral miRNA targets. This research has already led to novel insights into the role of viral miRNAs as well as the function of miRNAs in general (Grey et al PLoS Pathog. 2010 Jun 24;6(6):e1000967; 2007 Nov;3(11):e163). In addition previously unknown host virus interactions have been discovered through miRNA target identification. Because miRNAs can potentially target any cellular gene, and therefore any biological process, the research has the potential to impact on diverse aspects of virus biology and host virus interaction. The challenge for future research in this area is to develop a more detailed understanding of how these genes are involved in virus biology and why viruses target certain genes by miRNA regulation.
If you are interested in this research and would like to join the group as an MSc or PhD student please contact Finn Grey direct.