Biophysics

Cells in our body communicate with each other with complex signaling events.

Although these signaling events involve a multitude of signal transduction molecules, they are usually triggered by interactions between a ligand and a receptor in the plasma membrane. Investigation of spatiotemporal interactions between the signaling components in the membrane has so far been hampered by the complex structure of the cell membrane. The processes driving signaling in the plasma membrane involve not only the core protein components (such as receptors and ligands), but also membrane lipids, the underlying actin cytoskeleton, glycocalyx covering the membrane, intracellular protein scaffolds, and downstream interactors. This complexity is a major technical challenge in attempting to discern the impact of each individual component on the various steps of immune cell signaling. Related to this, in this vast complexity, it is very challenging to deduce insights on the physicochemical principles behind these processes.  Moreover, early phases of signaling where the ligands meet the receptors occur at very fast temporal (milliseconds) and small spatial (nanometers) scales, which further hampers thorough elucidation of these processes. Therefore, studies aiming at a mechanistic understanding of immune signaling processes require both advanced imaging techniques with nanometer and microsecond spatiotemporal resolution and well-defined biomimetic systems that can provide tuneable molecular specificity and complexity to pinpoint the role of each functional component as well as physical principles of signaling processes.

In our lab, we solve these problems by developing and using advanced imaging and synthetic biology tools to reveal the molecular mechanisms governing the cellular signaling.