PPHPI · Physical principles in host-pathogen interactions

In recent breakthrough publications, I developed quantitative models of accurate chemo-sensing in biological cells, as well as obtained important insights into how cells engulf and eat other cells and particles. The novelty of these works is the merging of the natural sciences of physics and biology for discovering general, overarching principles in biology. Now I propose to bring my research to a new level by tackling host-pathogen interactions, irrespective of established disciplinary boundaries.While individual signalling pathways are often well characterised in different cell types, an integrative view is largely missing. For instance, the chemical environments of pathogens are generally uncharacterised such as occurring in complex bacterial communities in an host organism. Furthermore, the strategies of how our immune cells sense and hunt their bacterial prey remain unknown. Specifically, how do they sense minute chemical signatures left by bacteria? Once an immune cell encounters a bacterium, what are the determinants of successful engulfment and destruction of the pathogen? To address these questions, I will investigate how bacteria perceive their environment with cell-surface receptors, including what chemical stimuli and gradients their sensory systems have adapted to by evolution. I will identify the strategies of cells for achieving highly accurate sensing, and study the dependence of engulfment on bacterial cell shape, stiffness, and ligand density. Answering these questions is of fundamental importance since it would identify how infections arise, spread and are cleared, with pharmaceutical applications in near sight.To conduct this research, the ERC Starting Grant would allow me, by assembling a cutting-edge and creative research team, to consolidate my research interests into one major stream for maximal impact. I would finally establish myself as an independent researcher, who delivers predictive and quantitative biology in Europe.""