Structure, Function and Modulation of Ion Channels.
Ion channels are the proteins that create the electricity in all living cells. Although a solitary ion channel protein possesses the machinery to generate an electrical signal, cells have evolved membrane-embedded partner proteins that associate with and fine-tune the electrical currents of ion channels to achieve the appropriate physiological function for that particular cell. The rhythmicity of the heart beat, maintenance of arterial tone and insulin release by b cells in the pancreas are all physiological processes that require a healthy association between ion channel and partner protein.
Our laboratory is investigating the structural motifs of these membrane-embedded protein-protein interactions as well as the molecular basis for the dramatic changes in ion channel function due to this association. Armed with this structural data, we aim to construct novel partner proteins and potentially small organic molecules designed to modulate ion channel function. One basic question the lab is interested in is how do two hydrophobic proteins selectively associate in the greasy confines of the membrane where the "hydrophobic effect" that usually brings water-soluble proteins together presumably cannot operate? By studying the ion channel/partner protein complex at the molecular level we hope to improve our current primitive understanding of membrane-embedded protein-protein interactions.
Because the study of membrane proteins poses unique challenges in protein biochemistry, the lab is developing lipomimetic reagents that specifically target proteins in the cellular membrane. We also rely on the powerful techniques of electrophysiology including single-channel recording, two-electrode voltage-clamp and the Xenopus ooctye expression system to address these structural, biophysical and physiological questions.
William Kobertz received his Ph.D. (1997) from the Department of Chemistry at MIT. He was a Howard Hughes postdoctoral fellow with Christopher Miller at Brandeis University from 1998-2001. Following his postdoctoral work, he joined the Department of Biochemistry and Molecular Pharmacology at the University of Massachusetts Medical School as a faculty member and is also a recipient of a Burroughs Wellcome Career Award in the Biomedical Sciences (2001-2005).