Understanding and engineering of complex biological systems are key challenges to the scientific community for addressing health problems, especially diseases. Studies of biological systems can vary in scale from molecules, cells, to entire organisms. Cells, as the basic building blocks of life, compose various biological entities of higher order and precisely control both structures and functions. Therefore, it is of vital importance to understand how cell functions and behaviors are regulated in order to engineer and manipulate cell behaviors. Recently, advances in molecular imaging technologies and synthetic biology approaches have enabled us to better detect and manipulate cell signals and behaviors, and provide a broad set of tools to influence and revolutionize basic research, medicine and therapy. In my dissertation, a general high-throughput platform has been established to systematically optimize biosensors and a new Src biosensor with high sensitivity has been developed accordingly. Combining fluorescence/Förster resonance energy transfer microscopy and laser scissors technology, the signaling transmission between neighboring cells and the underlying mechanism could thus be revealed, which could provide a cell model to understand intercellular communications and wound healing process. Furthermore, I have successfully developed, characterized and demonstrated specific molecular machineries to program cell behaviors by rewiring molecular signaling pathways, specifically immune responses in immune cells against cancer cells. These new tools and understanding may open a new avenue towards cancer therapy and lead to potential therapeutic strategies
