Yes, No, Maybe – decision-making in immunological signalling pathways

Abstract

Cellular signalling – the transmission and processing of information by cells – is an essential feature of life and critical to coordinating the immune response. Although the key molecular players in many pathways have been identified, we still often know very little about the mechanisms by which the same cell surface receptor can not only bind different ligands but also, most importantly, evoke a specific response to each of them. In my talk, I will discuss some of my previous work showing that cell topography influences T-cell receptor (TCR) signalling, pointing to a previously overlooked cellular mechanism ensuring receptor specificity. At AMOLF, my group now wants to explore whether similar mechanisms are also at the heart of other immunological pathways. To do so, we reconstitute signalling processes in model membranes, ultimately aiming to build a ‘minimal immune cell’: we want to learn how cells shape their membranes not only in response to signals, but also to detect and discriminate them. By combining this synthetic biology approach with tools from single-molecule biophysics and microfabrication, we can study signalling ligand-receptor interactions in lipid membranes using quantitative microscopy to generate data for new mathematical models. I will give a flavour of the projects that we have already started in the past months, in particular on ligand discrimination in cytokine (interleukine-2/-15) signalling and membrane remodelling in phagocytosis.