ULELAB

In particular, we focus on the roles of dynamic protein-RNA condensates, which form through large numbers of weak links. We wish to understand how these links enable selective RNA regulation, how they are rapidly modulated in response to cellular signals, how cross-regulation between proteins and RNAs in condensates contributes to cellular homeostasis, and how loss of such homeostasis contributes to neurodegenerative diseases... Many neurodegenerative diseases are associated with formation of toxic aggregates of TDP-43, which result from the strong propensity of TDP-43 for molecular condensation. We addressed the long-standing question of whether TDP-43 condensation is required for its RNA binding specificity and function. We created variants of TDP-43 with a gradient of condensation properties as evident by in vitro phase separation, and by imaging the condensates of TDP-43 in cells. We then used comparative iCLIP to find that the condensation of TDP-43 is required for its efficient..