Computational Microscopy of Cells

As an integral part of cell architecture, cell membranes are central to cell functioning. Comprising a heterogeneous mixture of proteins and lipids, cell membranes are constantly adapting their structural organization to regulate cellular processes. Malfunction at the level of lipid-protein interaction is implicated in numerous diseases , and hence, understanding cell membrane organization at the molecular level is of critical importance. Unfortunately, our current understanding is limited, which is due to the lack of methods for studying these fluctuating nanoscale assemblies in vivo at the required spatiotemporal resolution. An important tool for studying cellular processes is through molecular simulation, denoted computational microscopy. Computational microscopy has been used to study small membrane patches in isolation, but until now, cell membranes have not been simulated in their ‘natural’ context. I intend to apply computational microscopy at the whole-cell level, to study complex membrane structures and their function within the cellular environment. This requires challenging methodological innovations at the crossroads of biology, life sciences, physics, and chemistry. In this project, I will use advanced computational microscopy to study the interplay of membranes with their surroundings in a realistic cellular environment. The main goal is to establish a framework for the simulation, at molecular resolution, of entire cells and cell organelles.