Valiyaveetil Lab -- Research

MOLECULAR MECHANisMS OF POTASSIUM CHANNELS

We study K⁺ channels, which are integral membrane proteins that catalyze the selective conduction of K⁺ ions across biological membranes. While a great deal of research has been focused on these channels, fundamental questions regarding the mechanism of ionic selectivity and gating remain. We have developed a unique combination of methods to address these questions. Our methods include the use of chemical synthesis to introduce precise chemical changes in the channels, x-ray crystallography to determine the structural effects and electrophysiology to determine the functional effects of these changes.

Using this multidisciplinary approach we are presently investigating the mechanism of K⁺ selectivity and the process of slow inactivation.

CHEMICAL BIOLOGY OF POTASSIUM CHANNELS

Potassium channels play critical roles in a number of physiological processes including neuronal excitability, cellular signaling, neurotransmitter release and regulation of heartbeat. Molecules that target potassium channels are useful tools for investigations of the structure and physiological functions of these channels. We use our expertise in the chemical synthesis of K⁺ channels to develop K⁺ channel based biosensors for high throughput screening of molecule libraries to identify molecules that target these channels.

Our present focus is on the human voltage gated K⁺ channel, K_v1.3.  The K_v1.3 channels play an important role in the activation of human lymphocytes and inhibition of the K_v1.3 channel is regarded as a promising strategy for the treatment of T-cell mediated auto-immune diseases like multiple sclerosis.  The molecules that we identify using the biosensors that we will develop should therefore serve as lead compounds for the development of therapeutics for multiple sclerosis.