Jay Groves in Marseille @LAI
Published:
Jay Groves (U. Berkeley, USA) is visiting Marseille and LAI following the invitation that, together with the CiNAM, we extended to give a Centuri Seminar… link
… it is a real pleasure to host him and to have such insightfull and stimulating discussions about T cell activation, condensates, biophysics… immunobiophysics in a word !
His lab website : link
Hosted by: Kheya Sengupta (CINaM) and Pierre-Henri Puech (LAI).
Title: Phase transitions, mechanics, and stochastic timing in signal transmission form single T cell receptors
Abstract: The T cell receptor (TCR) signaling system is on the front line of the adaptive immune system’s ability to recognize foreign antigens. At the same time, TCR signaling mechanisms are a gold mine of interesting physics in molecular signaling processes. It has long been known that TCRs discriminate foreign from self antigen based on a kinetic proofreading process. More recent work has revealed that T cells are single molecule sensors and that the entire signaling process operates deep in the stochastic limit of molecular discreteness. My lab has been broadly focused on using imaging experiments to directly resolve the TCR signaling process–down to the single receptor level–and build a quantitative understanding of its mechanisms from this. These efforts have revealed an important role for a type of protein condensation phase transition to provide noise suppression and signal amplification. Perhaps most surprisingly, we have recently determined that these LAT condensates (as we and some others call them) consist of complete, yet entirely isolated, signaling systems. Individual LAT condensates form in response to single antigen-TCR binding events, and each condensate faithfully translates a successful TCR activation event into a single, cell-wide calcium spike. I will discuss these observations and our interpretation of how they provide a signaling mechanism with unique capabilities to suppress noise while achieving single molecule sensitivity. I will also discuss even newer results from our efforts to track the process of condensate nucleation by activated TCR–essentially watching the cellular decision to activate in real time.