BioHETER

Every biological system, whether it is a protein, a lipid bilayer, a nucleic acid or a receptor-ligand bond, can exist in a number of different forms or states. Therefore, a biological system is heterogeneous in nature. The origin of this heterogeneity can be due to differences in structure, conformational dynamics, and molecular nature of the individual components. Often hidden in ensemble average measurements, only the advent of single molecule techniques allowed us to directly explore and quantify this heterogeneity by observing molecules one at a time. The aim of this project is to decipher the nature of this heterogeneity. To reach this goal, we will measure the forces required to perturb individual biological systems. The force signature will provide information about the state of the system, allowing us to quantify heterogeneity. We will use nanotools to probe the forces required to unfold proteins, break bonds and punch membranes at high temporal resolution, first on isolated systems and then on living cells. This will require state-of-the-art nanotechnology with advanced control techniques and novel data analysis and mining algorithms. Theoretical modelling and simulations will allow us to interpret the results and re-configure the experiments to better understand the origins of the heterogeneity of each system. The expected results will shed light on almost all biological processes, from immune recognition during infection to pathologies involving protein aggregation.