Daniel L. Minor
Molecular Evolution of Novel Ion Channel Inhibitors and ActivatorsWe run on electricity. Brains, muscles, hearts, and senses all require electrical signals to function properly. Our research aims to understand the basic components of excitable cells that are responsible for generating electrical activity. To this end, we focus on understanding the structure, function, and regulation of ion channels from a high-resolution viewpoint. Our lab is multidisciplinary and combines approaches that include X-ray crystallographic studies, biochemistry, molecular biology, selection from combinatorial libraries, and electrophysiology to understand the basic mechanisms of how these proteins function and are regulated.
Ion channels are membrane proteins that allow cells to generate electrical signals. They are found not only in excitable cells like neurons and muscle, but are ubiquitous in biological systems. These proteins act as gates, specifically controlling the flux of ions across the cell's membrane in the response to a variety of stimuli including transmembrane voltage changes, ligand binding, and second messenger stimulation. Generally, channel proteins exist in one of two conformations, open or closed. In the open state, ion channels form a pathway that allows ions flow down their electrochemical gradients from one side of the cell membrane to the other. Control of ion flux in response to external stimulation, generates the fundamental signaling step that forms the basis for many biological processes such as the regulation of heartbeat, movement of muscle, regulation of hormone release from pancreatic cells, and the generation of thought. Many types of ion channels are known. Channels that specifically conduct potassium ions constitute the largest, most diverse family of ion channels and play key roles in the regulation of cell excitability. We are interested in understanding the mechanisms by which these proteins act. What are principal rules that govern ion channel structure? What is the nature of the conformational changes that accompany channel activation? How does a cell modulate channel activity through the action of proteins like kinases and GTPases? Can we develop new methods to modulate ion channel function in vivo? Addressing the molecular basis of these issues will be critical to understanding the roles of ion channels in larger signaling networks, like the brain, as well as understanding their misfunction in various human diseases.