Dissecting robustness mechanisms via signalling adaptation and trafficking plasticity during developmental and pathological cell migration

Robustness mechanisms are ubiquitous in biological systems where they act to ensure a stable outcome despite intrinsic (genetic) and extrinsic (environmental) variabilities. However, the underlying mechanisms are often unclear. In my proposed research, I will investigate the mechanistic basis of how systems deal with change in the context of cell migration during development, immune responses, and cancer invasion. Cell migration models I will use for my study include: the posterior lateral line primordium (pLLP) migration in development and macrophage recruitment during wound immune response in zebrafish, and invasion of cultured cancer cells. The main goals of the proposed original project are: (1) Characterizing the molecular mechanisms and network architectural designs that enable robust adaptation during cell migration in a multicellular organism, (2) Analysing the requirement of regulated membrane trafficking switching during chemotactic adaptation, and (3) Quantitatively defining the role of dynamic buffering in breast cancer spreading. To achieve these goals, an interdisciplinary approach will be taken, combining live imaging, genetics, biochemistry and phosphoproteomics. I will generate datasets bridging molecular, cellular, and tissue scales to obtain a systems level understanding of adaptive responses. This work will have broad implications for understanding chemotactic adaptation in development, physiology and disease.