Influenza and herpes viruses hijack a cell’s gene-reading machinery by blocking the normal “stop” signal that ends transcription, causing the cell to churn out long, useless RNA strands. This matters because scientists know viruses do this, but they do not understand exactly how. The mechanism is a blind spot in our knowledge of how these common pathogens evade immune defences. Without that detail, it is hard to design drugs that target the viral strategy directly. This project is fundamental science. It will use biochemistry, structural biology, and genetics to map the molecular interactions between influenza virus and the host’s transcription-termination system. The researcher will also run parallel experiments in yeast to uncover general principles of how termination factors can be modulated. If successful, the work will reveal a new layer of host–virus conflict. That knowledge could eventually point to antiviral targets that restore proper termination in infected cells. But the immediate payoff is a deeper understanding of a basic cellular process that viruses have learned to corrupt—the kind of insight that has historically opened unexpected routes to therapy.
View original technical description
Viruses employ various approaches to avoid host cell defence-mechanisms. In Herpes Simplex Virus 1 (HSV1) and Influenza A Virus (IAV) these include strategies to inhibit transcription termination. This leads to non-terminated readthrough transcripts, likely nuclear retained and untranslated. Exactly how viruses inhibit transcription termination, and how this promotes their survival and efficacy is currently unclear. Using my experience and expertise in transcription termination, I propose to systematically analyse the mechanism by which IAV alters 3’ end processing transcription termination and determine how this affects host gene expression. I will use biochemistry, molecular biology and structural biology, to identify the termination components affected by IAV, and reverse genetics to identify the IAV-component effecting termination inhibition. I will also employ sequencing of fractionated, cellular and ribosome-associated RNA to examine how virally-induced termination defects perturb mRNA-export and translation, as well as cell biology and genetics to identify the mechanisms and signalling cascades through which this change is realised. Finally, I will perform orthogonal studies in budding yeast to identify molecular mechanisms that can modulate the activity of transcription termination and RNA processing factors. Overall, my programme will scrutinize an under-explored yet fascinating mechanism to alter gene expression through modulation of transcription termination.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know