• BS 1991, University of Delhi, India
• MS 1993, University of Poona, India
• PhD 2000, National Center for Biological Sciences, Bangalore, India (M.K. Mathew)
• Postdoctoral, 2000-06, University of California, Los Angeles (Francisco Bezanilla)
Honors & Awards
• Scientist Development Grant, American Heart Association, 2005
• Shaw Scientist Award, 2008
• UW-Madison Vilas Associate Award, 2012
• Cranefield Award, Society of General Physiologists, 2013
• UW-Madison Romnes Award, 2015
The voltage-activated ion channel superfamily (VGICs) constitutes a large class of membrane proteins that are primarily responsible for sensory transduction and electrical signaling. The members of this superfamily respond to a variety of stimuli that range from voltage and temperature on one hand to calcium, cyclic nucleotides and phosphoinositides, on the other. Our goal is to understand at a fundamental level how the interplay of structure and dynamics determines the function of these ion channels and ultimately defines electrical excitability of biomembranes. We employ an array of biophysical techniques that includes but limited to electrophysiology, fluorescence spectroscopy, single-molecule methods and crystallography to address the molecular mechanisms of gating and modulation. Along with these experimental approaches, we are also developing analytical tools to quantify and measure energetics of ion channel activation.
One broad area of research in the Chanda lab is to understand the origin of molecular forces that drive conformational changes responsible for coupling a sensing domain to the ion pore. A protein is described as a complex meshwork of interactions where only some of which are involved in conformational coupling. We have recently described a set of mathematical equations that enables us to calculate activation and coupling energies in a model-independent manner. Early work from Chanda lab resulted in identification of the molecular determinants of conformational coupling in voltage-activated sodium channels (see Figure 1).
Figure 1. Voltage-clamp fluorimetry to identify mutants that are involved in coupling voltage-sensor to pore opening in two interfaces (marked boxes). This approach simultaneously tracks channel opening and voltage-sensor movement in response to voltage jumps. (Adapted from Muroi et. al. (2010) Nature Structural and Molecular Biology).
Some members of this superfamily are exquisitely sensitive to temperature stimulus and are considered to be the primary thermosensors in the human body. We want to understand the physiochemical basis of temperature-sensitivity of these ion channels. We have recently described the design principles of a heat-sensitive and a cold-sensitive ion channels.
. Design of a temperature-sensitive ion channel from Chowdhury et. al. (2014) Cell 158, 1148-1158.