Robust workflow for sub-volume averaging of tomographic data. (360G-Wellcome-090895_Z_09_A)

Viruses and their interactions with host cells provide attractive model systems for studying macromolecular interactions. The structural design of viruses provides a remarkable example of simplicity and functionality in biological systems. Viral particles work as highly effective molecular devices in the transfer of the viral genome and accessory proteins from infected to non-infected cells. I intend to address dynamic interactions of viral and cellular protein complexes leading to membrane curv ature perturbations in their native environment using cryo electron tomography and complementary approaches. We will concentrate on three major systems - (i) Viral and eukaryotic fusion proteins, (ii) cell-cell-transmission of retroviruses and (iii) cellular membrane coats - and study for each of them a particular aspect of membrane curvature modulation at various levels of detail and complexity. We will take advantage of the properties and specificities of the individual systems to understand t he underlying mechanistic properties of membrane remodelling. Furthermore, computational and imaging tools will be developed for the efficient analysis of the structural interactions of the macromolecules. The combination of systems and approaches ultimately aims to integrate high resolution structural information with live cell imaging to achieve a spatio-temporal description of complex biological processes thereby revealing native structure-function relationships.