Baron Chanda

Baron Chanda

Associate Professor

(Also Neuroscience)

9457 Wi Institute for Medical Research

1111 Highland Ave.

Madison, WI 53705

Phone: (608) 265-3936

Email: chanda@wisc.edu


 
Education
• 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

 

Research Interests

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).


chanda 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.

Figure 2. Design of a temperature-sensitive ion channel from Chowdhury et. al. (2014) Cell 158, 1148-1158.


 

Publications of Note

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• Goldschen-Ohm, MP, and Chanda, B. (2015) More than S4? How to open a proton pore. Nature Structural and Molecular Biology, in press.

• Chowdhury, S., Haehnal, BM, and Chanda, B. (2014) A self-consistent approach for determining pairwise interactions that underlie channel activation. Journal of General Physiology 144: 441-455.

• Chowdhury, S, Jarecki, BW, and Chanda, B. (2014) A molecular framework for temperature-dependent gating of ion channels. Cell 158, 1148-1158. Highlighted in “Building a temperature-sensitive ion channel” by Ming-Feng Tsai and Christopher Miller. A video abstract was featured as PaperFlick in the online issue.

• Oelstrom KM, Goldschen-Ohm, MP, Holmgren, M, and Chanda, B. (2014) Evolutionarily conserved intracellular gate of voltage-gated sodium channels. Nature Communications 5:3420. doi:10.1038/ncomms4420.

• Jarecki, B.W., Zheng, S.L., Zhang, L., Li, X., Zhou, X., Cui, Q., Tang, W., and Chanda, B. (2013) Tethered spectroscopic probes estimate dynamic distances with sub-nanometer resolution in voltage-dependent potassium channels. Biophysical Journal 105(12) 2724-2732. Highlighted in “New rule(r)s for FRET” by Frank Bosmans (ibid. Pgs. 2619-2620). Also featured in research highlights in Nature Chemical Biology vol. 10, March 2014 (Pg. 169).

• Goldschen-Ohm, MP, Capes, DL, Oelstrom, K, and Chanda, B. (2013) Multiple pore conformations driven by asynchronous movements of voltage-sensors in a eukaryotic sodium channel. Nature Communications 4:1350. doi: 10.1038/ncomms2356.

• 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.Highlighted in “Model-free energy for voltage-gated ion channels” by Christopher Miller (ibid. Pgs 1-2)

• Capes, D., Arcisio-Miranda, M., Jarecki, B.W., French, R., and Chanda, B. (2012) Gating transitions in the selectivity filter region of a sodium channel are coupled to domain IV voltage-sensor. Proceedings of the National Academy of Sciences (USA) 109(7): 2648-53.

• Muroi, Y., Arcisio-Miranda, M., Chowdhury, S., and Chanda, B. (2010) Molecular determinants of coupling between the domain III voltage-sensor and pore of a sodium channel. Nature Structural and Molecular Biology 17(2): 230-217.

• Chowdhury, S., and Chanda, B. (2010) Deconstructing thermodynamic parameters from site-specific observables in a coupled system. Proceedings of the National Academy of Sciences (USA) 107(44): 18856-18861.