Epigenetic Regulation of Viruses

Viruses are posing one of the biggest threats to human existence and their potential to influence public health depends on multiple factors e.g. cellular interactions of viruses with the susceptible hosts. Recent advances in cellular epitranscriptome (biochemical modifications of the RNA within a cell) have unravelled that genomes of several medically important viruses such as influenza, HIV and ZIKA carry m6A (addition of a methyl group to the N6 position of adenosine) epigenetic motif. The m6A is the most prevalent epigenetic mark of cellular mRNA and viral RNA, and up to 10 m6A motifs can be identified in highly regulated RNAs.

The m6A modifications play crucial roles in the regulation of mRNA function at multiple steps, including splicing, stability, translation, and secondary structure. Our recent work has identified enrichment of m6A marks at crucial sites of viral and host RNA, highlighting their roles beyond RNA metabolism. In this project, we will apply cutting-edge molecular biological approaches to map the epigenetic landscape of influenza viral RNA at single-nucleotide resolution. Since influenza virus carry zoonotic potential (transmission of viruses from animal to human), we will evaluate the roles of m6A in the influenza virus pathobiology in chicken, pig, bats and human and draw structural and functional differences among these hosts.

The generated knowledge will provide a new framework for understanding the relationship of epigenetics with viral pathogenesis and transmission, and will lay foundation to exploit host/viral epigenetics in designing novel vaccines and therapeutics.

Training Potential:

The student will develop a broad range of technical skills in molecular virology, reverse genetics, genome editing (CRISPR/Cas9), novel RNA-tagging through C2c2/Cas13a, bioinformatics and functional genomics.

Applicants are invited from a range of infection biology/cell biology/biomedical backgrounds; although an enthusiastic approach to the proposed research, area is essential. Laboratory experience covering any of the techniques mentioned above is desirable. For informal enquiries, which are encouraged, please email Dr Muhammad Munir at [Email Address Removed].

Environment:

Research at Dr Munir’s Lab at Lancaster University focused on viral pathobiology, viral antagonism of immune responses and host factors that limit virus replication in diverse hosts with primary aim to understand molecular mechanisms of inter-species pathogenesis of viruses (i.e. zoonotic viruses, viruses that transmit from animal to human). Specifically, using model influenza viruses we are aiming to explore host and viral RNA biology (sensing – interferon responses, epigenetics and gene regulation) and define structural and functional differences in human and animals (e.g. birds and bats), which determine the transmission dynamics of animal viruses to human

Applications are made by completing an application for PhD Biomedical and Life Sciences starting in January 2019 through our online application system. Closing date: midnight 23rd November 2019.