Baron Chanda

Biophysical mechanisms of gating and regulation of voltage-gated ion channels: Structure, dynamics and function

 The primary focus of the Chanda lab is to understand the structure and dynamics of voltage-gated ion channels (VGICs). VGICs are a large superfamily of ion channels involved in key biological processes ranging from nerve action potential to immune response in animal cells. In higher eukaryotes, members of this superfamily also serve as primary biosensors of external stimuli such as heat, cold, mechanical touch and membrane potential. In general, the biophysical mechanisms that determine function of VGICs and their response to stimuli remains poorly understood.

Previous studies from our group have led to development of quantitative formalisms to estimate free energy of channel activation in a model independent manner and measure interaction energies involved in channel gating (1,2). Much of our current research utilizes single molecule methods such as single channel electrophysiology, single molecule fluorescence spectroscopy and single particle cryo-EM techniques to understand how structural dynamics of these ion channels determine their biological function. These studies will ultimately provide new insights into the fundamental mechanisms that underlie channel gating. These emerging ideas help design ion channels with novel function (3, 4) and may someday lead to development of new class of therapeutics.

Lab website: http://bclab.neuro.wisc.edu/

Representative publications:

Chowdhury, S., and Chanda, B. (2012) Estimating the voltage-dependent free energy change of ion channels using the median voltage of activation. Journal of General Physiology 139 (1): 3-17.

Chowdhury, S., Jarecki, B.W., and Chanda, B. (2014) A molecular framework for temperature-dependent gating of ion channels. Cell 158, 1148-1158.

Fernández-Mariño, A.I., Harpole, T., Oelstrom, K., Delemotte, L., Chanda, B. (2018) Gating interaction maps reveal a noncanonical electromechanical coupling mode in the Shaker K+ channel. Nature Structural and Molecular Biology 25:320-326. doi:10.1038/s41594-018-0047-3.

Cowgill, J., Klenchin, V.A., Alvarez-Baron, C., Tewari, D., Blair, A., Chanda, B. (2019) Bipolar switching by HCN voltage-sensor underlies hyperpolarization activation. Proceedings of the National Academy of Sciences (USA) 116(2) 670-678.