MRC National Institute for Medical Research, London
Science for Health
This project is now closed
Structural studies of influenza virus by cryomicroscopy
Project supervisor: Peter Rosenthal (Physical Biochemistry)
Our laboratory uses electron microscopy and other physical and structural techniques to understand problems in virology and virus interactions with cells. We are interested in understanding how influenza virus enters the cell by binding to cell surface receptors and how the virus membrane fuses with host membranes. We have recently performed high resolution studies of influenza virus ultrastructure by cryomicroscopy which has shown us the internal architecture of the virus as well as the structure of envelope glycoproteins in situ (Calder et al, 2010).
The main focus of the student project is to directly image influenza virus and cell architecture during infection of mammalian cells in culture. Virus-infected cells will be plunge-frozen and studied by electron cryotomography (using procedures developed in our laboratory as described in Berriman et al, 2009) providing three-dimensional maps of the periphery of the infected cell. In our previous study, we have observed structural changes in the virus at the low pH normally encountered in endosomes. Specifically, we are interested in imaging the role played by the influenza haemagglutinin in membrane fusion and the concomitant changes in the internal structure of the matrix layer that facilitate fusion and release of RNP segements into the cell. Our understanding of the infection processing in vivo will be complimented by parallel studies of entry steps in vitro using model membranes and subcellular fractionation.
We are part of the Division of Physical Biochemistry, which possesses a state-of-the art cryomicroscopy facility and interact with research groups employing single molecule imaging techniques including light and force microscopy. We have close collaborations studying related problems with the Divisions of Structural Biology, Infections and Immunity, and Neurosciences.
References
- Calder, LJ; Wasilewski, S; Berriman, JA and Rosenthal, PB (2010)
Structural organization of a filamentous influenza A virus.
Proceedings of the National Academy of Sciences of the United States of America 107, 10685-10690 PubMed abstract - Berriman, JA; Li, S; Hewlett, LJ; Wasilewski, S; Kiskin, FN; Carter, T; Hannah, MJ and Rosenthal, PB (2009)
Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells.
Proceedings of the National Academy of Sciences of the United States of America 106, 17407-17412 PubMed abstract
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