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Our ultimate goal is to understand how cells, the basic units of life, sense changing environments and orchestrate specific responses to carry out life processes. The past decades have seen tremendous progress in identifying the molecular components that constitute the structural, biochemical and mechanical networks that control various life processes. Less well developed is our understanding of how these components are precisely regulated to achieve the functional specificity within a living cell, which may be simultaneously reacting to multiple inputs from the changing environment. It has been increasingly clear that the key lies in the spatiotemporal information encoded in a particular cellular context.
We are investigating the molecular mechanisms and functional roles of such spatiotemporal regulation by taking a “native biochemistry” approach. This allows us to unravel chemical mechanisms of life processes in the framework of cellular time and space, where molecular changes can be directly linked to functional effects. Combing genetically encoded fluorescent biosensors, superresolution imaging, targeted biochemical perturbations and mathematic modeling, the Zhang laboratory is investigating the spatiotemporal regulation of cAMP/PKA, Ca2+/calcineurin, PI3K/Akt/mTOR, Ras/ERK and AMPK pathways, in the context of energy metabolism, axon polarization and genesis, insulin secretion by β cells as well as tumorigenesis.