Influenza A viruses (IAV) are serious threats to human health, causing a contagious respiratory disease. I study the interaction between IAV polymerase and a cellular protein Rab11a, which is needed for successful transport of the IAV genome to the cell plasma membrane, where new virions assemble.
We use cryo-3D-SIM to observe the location of fluorescently tagged IAV polymerase in the cytoplasm of infected cells expressing fluorescently tagged Rab11a. We also study how IAV remodels the cytoplasmic architecture of infected cells using cryo-soft X-ray tomography. Together these techniques will ultimately expand our knowledge of host and virus biology both at the level of cell ultrastructure and in molecular detail.
Ninety percent of people that possess a life-long herpes simplex virus (HSV) infection are completely unaware of it. The other ten percent exhibit mild or severe symptoms of viral inflammation. Our research aims to uncover the mechanisms behind virus production in human cells. We are specifically interested in how the virus remodels cellular architecture to assemble its envelope (the outer layer of the virus).
The multi-modal imaging capabilities at B24 are central to our research strategy. We use cryo-3D-SIM to observe the localization of the virus in different organelles at super resolution and we study alterations in the structure of these organelles using cryo-soft X-ray tomography. Together these techniques provide a new method to study the complicated interplay between viral and cellular machinery during virus propagation.
This PhD project is a collaboration between B24 and the Department of Pathology, University of Cambridge (Dr Stephen Graham and Dr Colin Crump).
Patrick is currently completing his masters year in industry at Diamond. His research is focused on understanding Chlamydia via correlative light and X-ray microscopy. This involves cryo-SIM and cryo-soft X-ray tomography (cryo-SXT) of infected cells at B24. He has also been improving methods for the reconstruction and segmentation of tomograms (IMOD, SuRVoS and ImageJ).
His aim is to achieve semi-automated segmentation of tomograms with the aid of macros which obtain statistics on the volume and distribution of Chlamydia. In parallel, he has performed cryo-electron tomography on his samples at eBIC to test how this cryo-bioimaging method can be best integrated with cryo-SXT.
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