Structural Biology Program in Physiology
Every cell, prokaryotic and eukaryotic alike, is subject to its environment. A cell needs to continuously respond to chemical, physical and biological extra-cellular stimuli. This is achieved by proteins that reside within the membrane, and that are responsible for how a cell exchanges information with the outside. For example, there are channels that regulate the flux of ions or nutrients across the membrane, and receptors that are activated by specific ligands to elicit an intra-cellular response.
A snapshot of any and every one of such molecules at the atomic level is of invaluable importance in understanding how the protein in question works in both physiological and pathological states of the cell.
Membrane proteins constitute 30% of all human proteins and ~60% of drug targets. Yet, they only represent less than 1% of protein structures determined to date. Obtaining a macromolecular structure typically entails measuring X-ray diffraction data from suitable protein crystals. Producing crystals sufficiently ordered to yield quality X-ray diffraction thus allowing structural investigation, is the key and most problematic step. This is especially difficult for membrane proteins because they naturally reside in the cellular membrane, and therefore have to be extracted by detergents for purification and crystallization. Detergents are a poor substitute of the lipid bilayer and often lead to protein destabilization and denaturation.
The Structural Biology Program within the Department of Physiology and Cellular Biophysics strives to determine high-resolution structures of the main protein components involved in cellular signaling events. The program brings together the expertise of Dr Wayne A. Hendrickson, Dr Filippo Mancia, and Dr Ming Zhou and their respective laboratories.
Wayne A. Hendrickson, University Professor, HHMI investigator and Violin Family Professor of Physiology and Cellular Biophysics, has a deep and long withstanding interest in determining protein structure through X-ray crystallography. Membrane receptors, and proteins involved in signal transduction cascades are amongst many of the areas he investigates.
Filippo Mancia, Assistant Professor of Physiology & Cellular Biophysics, primarily studies the structure and function of membrane proteins involved in both the physiology and pathology of neurobiologically-relevant processes. His main interest lies in understanding the neuronal response triggered by the release of neurotransmitters.
Ming Zhou, Assistant Professor of Physiology & Cellular Biophysics, studies physiological functions of ion channels and transporters that are important for cardiac and neuronal functions.
Qualified graduate students and postdoctoral scientists are encouraged to apply for positions
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