Cryo-electron tomography to study virus or vesicle assembly.
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We are improving and applying methods for cryo-electron tomography, correlative light and electron microscopy and image processing. These methods have the power to reveal the 3D structures of proteins and membranes under close-to-native conditions, in heterogeneous environments, including inside cells: “in-situ” structural biology!
In the group we are interested both in methods development, and in using these methods in two areas of biology. The first area is the assembly and maturation of important enveloped viruses such as HIV-1 and influenza. How do the viral components interact to assemble a new virus particle? How does the virus particle mature to become infectious? How does the mature particle enter a new cell? The second is the formation of coated membrane trafficking vesicles such as clathrin and COPI. These are extraordinary self-assembling machines: the protein building blocks must interact with one another to collect all relevant components and the cargo together at the budding site, they must reshape a lipid bilayer to form the bounding membrane of the vesicle, and they must drive membrane scission to release the vesicle from the donor membrane. For viruses and vesicles we wish to obtain a mechanistic understanding of these processes by visualizing them as in vitro and in cells, where possible obtaining atomic detail.
Depending on the experience and interests of the student, the focus of the project could be directed towards the biological, technical, or computational aspects. The methods used will include cryo-focussed ion beam milling, electron tomography and computational image processing, as well as other complementary techniques. This project will address either HIV-1 or membrane trafficking vesicles. The PhD student will study the assembly process and the subsequent structural changes required for function.
Mattei, S., Glass, B., Hagen, W.J., Kräusslich, H.G. and Briggs, J.A (2016)
The structure and flexibility of conical HIV-1 capsids determined within intact virions.
Science 6318: 1434-1437.
Schur, F.K., Obr, M., Hagen, W.J., Wan, W., Jakobi, A.J., Kirkpatrick, J.M., Sachse, C., Kräusslich, H.G. and Briggs, J.A. (2016)
An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.
Science 353(6298): 506-508
Dodonova, S.O., Diestelkoetter-Bachert, P., von Appen, A., Hagen, W.J., Beck, R., Beck, M., Wieland, F. and Briggs, J.A. (2015)
VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly.
Science 349(6244): 195-198