Spatiotemporal control of cytoskeletal remodeling in lymphocytes

To effectively combat infections and malignant cells, T cells must rapidly migrate through tissue, efficiently scan targets for abnormalities, and kill. These functions all depend on the concerted remodeling of their actin cytoskeleton. Actin remodeling is highly complex, influenced by many internal and external signals, and it remains unclear how T cells integrate this information to achieve these key functions and ensure a successful immune response. In this proposal, I aim to visualise and manipulate signaling cascades and external signals that control actin dynamics, and relate this to functional outputs involving T-cell migration, target cell scanning, and activation. This will be achieved using a combination of tuneable reconstituted environments, biosensors, optogenetic manipulation, cutting-edge light-sheet microscopy, and computer vision approaches. Understanding the signaling networks that regulate cytoskeletal remodeling may uncover novel ways to control T-cell function for therapeutic benefit.