Studying biophysical mechanisms of T cell activation at the single molecule level

In the laboratory for Molecular and Cellular Biophysics at the Racah Institute of Physics, we aim to develop a fundamental understanding of critical mechanisms of cell activation in health and disease in single molecule detail. Ultimately, such a level of understanding could serve to identify novel and efficient ways of intervening in aberrant signaling pathways and cellular malfunctions. To overcome current limitations in research techniques, we rely on cutting-edge microscopy techniques at the single molecule level of intact cells on functionalized interfaces, advanced statistical methods and quantifiable models based on physics of complex systems. Research in our lab is currently focused on the activation of T cells, which play a central role in mounting adequate immune responses to foreign pathogens.

In our lab, we develop and apply photoactivated localization microscopy (PALM) in multiple colors. This method permits the study of signaling complexes in single molecule detail in intact cells with resolution down to ~20nm. Previous work has resulted in several intriguing findings, such as that signaling complexes at the plasma membrane of T cells have nanoscale structure and organization that facilitate intact cell activation. PALM imaging of three molecular species in locations of high molecular densities will further allow us to study the complexity of molecular interactions, including potential cooperativity or competition in molecular binding.