The laboratory of Immunology (Department of Virology, Parasitology, Immunology) of the Faculty of Veterinary Medicine at Ghent University (Salisburylaan 133, 9820 Merelbeke, Belgium) is seeking a highly motivated and enthusiastic PhD student to join our dynamic research team and to initiate his/her PhD research from September 2020 onwards.
Profile of the candidate
Herpesviruses are extremely successful pathogens, causing lifelong infections of their host. Evolution has shaped fascinating interactions between these pathogens and their host and host cells. Alphaherpesviruses represent the largest subfamily of the herpesviruses, and include important and closely related pathogens of man (e.g. herpes simplex virus 1 and 2 (HSV1&2) and varicella zoster virus (VZV)) and animal (e.g. pseudorabies virus in pigs (PRV)).
Protein synthesis in eukaryotic cells is carefully regulated. Epigenetic changes (e.g. histone modifications and DNA methylation) affect transcription efficiency. Over the past years, it has become clear that another layer of regulation of protein synthesis consists of chemical modifications of mRNA, collectively called the epitranscriptome. The epitranscriptome regulates e.g. mRNA export from the nucleus, mRNA degradation rates and mRNA translation efficiency. The most abundant internal mRNA modification is m6A methylation, which is carried out by the m6A writer complex (including METTL3, METTL14 and WTAP) and which can be removed via m6A erasers like ALKBH5. Particular proteins (including YTH proteins) serve as m6A readers, recognizing m6A modifications in RNA and subsequently affecting RNA biology.
Recently, our research team at Ghent University has discovered that alphaherpesvirus infection has a dramatic and unprecedented impact on m6A methylation of mRNA and on the fate of m6A-methylated host cell mRNA. In brief, we discovered that infection of cells with alphaherpesviruses like HSV1 and PRV leads to rapid and massive degradation of m6A-methylated host transcripts and, at the same time, to modification of the m6A writer complex. We have identified different viral and cellular proteins involved in these processes. These findings shed entirely new light on the interaction of (herpes)viruses with host cells and our understanding of m6A mRNA methylation and open up completely novel avenues towards the development of antiviral strategies.
The aim of the PhD research is (i) to unravel the complexity and mechanisms of the impact of alphaherpesvirus infection on the host cell epitranscriptome, (ii) to understand the consequences of these virus-induced changes of the epitranscriptome for virus and host and (iii) to design strategies to interfere with these viral modifications of the epitranscriptome. The data of this PhD research will generate novel insights in the domains of virology, molecular biology, cell & RNA biology and immunology and will provide valuable information with regard to the development of new antiviral strategies.
How to apply
Send your motivational letter and CV via email to Prof. H. Favoreel ([email protected] ) and ir. Robert Jansens ([email protected] ) at the latest by Monday June 1, 2020 (job opening may close early whenever a successful candidate is selected).
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