Cells constantly send and receive signals through an organelle centrally involved in communication, the plasma membrane. A quantitative understanding of these phenomena is currently lacking. Indeed cell signaling has been mostly investigated qualitatively, mainly focusing on the components and interactions within signaling networks. The innovative concept of the INFORM (INformation Flow and ORganization at the Membrane) project lies in its effort to jointly explore signaling mechanisms at the quantitative level and establish their functional/physiological relevance in vivo. To achieve this highly innovative and ambitious program, in the framework of INFORM we have built an interdisciplinary network on campus, gathering biologists, physicists and mathematicians in order to broaden and deepen our understanding of cell signaling. New experimental assays, imaging tools and mathematical models will be developed to specifically address signaling issues in their quantitative aspect.
Specific projects address the quantitative phenomenology of signalization (organization and dynamics, aim 1). Other projects address the regulation of signaling by mechanics (aim 2) and by trafficking (aim 3):
• Research aim 1: Quantitative phenomenology of signaling. How proteins involved in biochemical and mechanical signaling (signaling complexes) are organized at the cell surface? How is their dynamics involved in signaling? We will define and correlate several quantitative features of signaling complexes such as molecular structure, density, clustering, interaction with ligands, or diffusion with specific cellular models and imaging tools.
• Research aim 2: Signaling regulation according to mechanics. How mechanical stimuli modify signaling organization and dynamics? We will measure forces involved in adhesion (E-cadherin), migration (integrins) or T cell receptor activation. We will measure the impact of applied forces on signal organization.
• Research aim 3: Signaling regulation according to trafficking. How trafficking mechanism regulate signaling? We aim at linking receptor complex trafficking and downstream signaling by studying the role of ubiquitination and how pathogens manipulate innate immune receptors.