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The overall goal of our laboratory is to understand the process of information flow in cell signaling systems at atomic detail. Specifically, we see two fundamental biological problems that must be solved to enable further progress in understanding general principles of cell signaling.
- How do complex energetic properties of proteins (allostery and binding specificity) arise from properties of their 3-dimensional structure? Information transfer and exchange in signaling networks amounts to an ordered series of regulated localized binding and catalyzed reactions. At the single protein level, these molecular interactions typically cause a local free energy change at a specific site that then propagates through the structure to impact distant sites that mediate downstream signaling. The central unsolved problem is to understand how energetic perturbations distribute in protein structures by discovering the principles that operate in the process of evolution to establish reliable communication channels between functional surfaces.
- How are networks of proteins designed in cells to deliver efficient regulated signaling? We use the Drosophila photoreceptor cell as the model system, largely due to the availability of excellent high-resolution methods for genetic, physiological and biochemical dissection of visual transduction, a G protein-coupled phosphoinositide signaling system. The current challenge is to understand the macroscopic principles of assembling signaling components into functional modules. Our approach has been to isolate small sub-networks of signaling proteins and to understand how these act as modular units in providing for the impressive functional properties of the photoreceptor cell.
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