Influenza viruses are important human and animal pathogens; they cause widespread clinical and veterinary disease and have a considerable economic impact. Our laboratory focuses on the fundamental molecular mechanisms of influenza virus replication, aiming to understand the molecular determinants of host range and virulence of influenza viruses.
Specifically, we address questions ranging from how the influenza virus RNA polymerase transcribes and replicates the segmented negative-sense viral RNA genome in the nucleus of the infected cell to how the RNA genome is exported from the nucleus and assembles into infectious progeny virus particles. We are also interested in the role of host factors in viral replication as well as in understanding the effects of virus infection on the host cell, the molecular mechanisms of innate immune sensing and host cell responses to viral infection. Our group collaborates with structural biologists, physicists, chemists and immunologists using an interdisciplinary approach including molecular and cell biology, proteomics, single molecule and super-resolution microscopy, structural biology (x-ray crystallography and cryo-electron microscopy), and virology (reverse genetics).
This project builds on our recent success in expressing and purifying large amounts of recombinant influenza virus RNA polymerases from type influenza A, B and C viruses and their structural analysis by x-ray crystallography and cryo-electron microscopy (Fan et al Nature 2019), our progress in understanding the structure of the influenza virus RNA genome and its assembly into virions (Dadonaite et al Nat Microbiol 2019), and our discovery that defects in viral RNA genome replication result in the generation of aberrant viral RNAs that lead to the activation of innate immune responses via detection by the cellular sensor RIG-I (te Velthuis et al Nat Microbiol 2018). Depending on the experience and interests of the student, the focus of the project could be directed towards the structural and functional aspects of the RNA polymerase or the interplay between the RNA polymerase and the host cell.
4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See https://www.path.ox.ac.uk/content/prospective-graduate-students for full details and to apply.
Fan H, Walker AP, Carrique L, Keown JR, Serna Martin I, Karia D, Sharps J, Hengrung N, Pardon E, Steyaert J, Grimes JM and Fodor E (2019) Structures of influenza A virus RNA polymerase offer insight into viral genome replication. Nature 573(7773):287-290.
Dadonaite B, Gilbertson B, Knight M, Trifkovic S, Rockman S, Laederach A, Brown L, Fodor E, Bauer DLV (2019) The Structure of the Influenza A Virus Genome. Nat Microbiol 2019 Jul 22 [Epub ahead of print].
te Velthuis AJW, Long JC, Bauer DLV, Fan RLY, Yen HL, Sharps J, Siegers JY, Killip MJ, French H, Oliva-Martín MJ, Randall RE, de Wit E, van Riel D, Poon LLM, Fodor E (2018) Mini viral RNAs act as innate immune agonists during influenza virus infection. Nat Microbiol 3(11):1234-1242.
te Velthuis AJW, Fodor E (2016) Influenza virus RNA polymerase: insights into the mechanisms of viral RNA synthesis. Nat Rev Microbiol 14(8):479-493.
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FTE Category A staff submitted: 223.80
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