Viruses hijack the machinery that bends and fuses cell membranes, and this project will use advanced cryo-electron microscopy to watch them do it in real time, in their natural environment. This matters because membrane fusion is the critical step that allows enveloped viruses like influenza and HIV to enter cells, and non-enveloped viruses to break in without a lipid coat. It also governs how large viral cargoes escape the nucleus. Current structural methods often freeze viruses in artificial conditions, missing the dynamic, curved shapes membranes take during infection. This programme will capture those shapes directly, using three model systems: an enveloped virus fusing with a cell, a non-enveloped virus entering a cell, and a herpesvirus exiting the nucleus. If successful, the research will reveal the fundamental mechanical principles of membrane remodelling—a process that underpins not just viral infection but also cell division, neurotransmitter release, and hormone secretion. This is primarily curiosity-driven fundamental science. A deeper understanding of how proteins deform lipid bilayers could, in the longer term, inform the design of antiviral drugs that block fusion, or synthetic biology tools that control membrane shape on demand.
View original technical description
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.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know