Many biological processes, ranging from gene expression, apoptosis, cell proliferation to higher-order processes such as vision, memory, and learning, necessitate that a cell "be" aware of its environment. These processes involve transmission of signals across the plasma membrane. These signals are often transmitted through membrane protein receptors that connect the inside of the cell to the extracellular "world". There exist many classes of membrane receptors that have evolved to recognize a variety of signaling entities (ligands) such as ions, hormones, or even photons.
Ligands generally interact with their target receptor on or near the extracellular side of the plasma membrane. This recognition event elicits in turn one or more structural changes in the receptor. The structural changes are allosteric and lead to the activation of other protein receptors. In this way a complex intracellular signaling cascade is initiated until the intended biological response has been produced.
Our lab is interested in elucidating how some of these receptors, accomplish the transmission of the extracellular signal. Specifically, we seek to understand and to characterize what conformational changes a receptor undergoes following the recognition of the ligand, how these conformational changes support the transmission of the signal across the membrane, and how the conformational changes and putative downstream interactions of the receptor affect its interaction with the ligand. To this end, we apply and develop a variety of bioinformatics, theoretical and computational approaches. The objective is to obtain meaningful mechanistic hypotheses that can then be tested experimentally.
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Key Words: Membrane proteins, Molecular recognition, Allostery, Signal Transduction, Disease