Membrane modulation in crucial virus-host interactions. (360G-Wellcome-107806_Z_15_Z)

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 and machineries work as highly effective molecular devices to mediate membrane traversal to transfer viral genomes and accessory proteins into and out of cells and their sub-compartments. I here address dynamic interactions of viral and cellula r protein complexes leading to perturbations of the curvature of membranes. Our analyses will emphasize interactions in their native context using electron cryo-tomography and complementary approaches. We will concentrate on three major themes: (i) Membrane fusion of an enveloped virus, (ii) Cellular entry of a non-enveloped virus, and (iii) Nuclear egress of large viral cargoes. Moreover, image analysis tools will be further advanced to ensure a validated analysis of the data. Each theme will target a particular aspect of membrane curvature modulation and will cover different levels of detail and complexity. The programme builds on our recently established series of dedicated experimental systems for studying membrane proteins in their native environment. Combining these with a hybrid approach, integrating imaging of dynamics with interaction mapping and high-resolution structural information, we aim to unravel the underlying mechanisms of membrane remodelling. A common theme in all three lines of research is membrane fusion. We will take advantage of the properties and specificities of the individual systems and integrate the results to generalise common features and to elucidate some of the pivotal questions in this basic cellular process.