Baron Chanda, Ph.D.

Professor
Anesthesiology

Biochemistry, Biophysics, and Structural Biology Program
Neurosciences Program

  • bchanda@wustl.edu

  • https://chandalab.wustl.edu

  • Mechanisms and Design Principles of Ion Channel Function and Gating

Research Abstract:

Research in the Chanda Lab focuses on structural mechanisms that underlie gating of members of the voltage-dependent ion channel family. Our overarching goal is to understand the interrelationships between structure, function and dynamics in order to develop an integrated view of how ion channels work. If we are successful in this endeavor, we will be able to engineer new ion channels that exhibit exotic behavior or create small molecules that may selectively repair defective ion channels. Defects in ion channels underlie diseases such as cardiac arrhythmias, generalized epilepsies, cystic fibrosis and polycystic kidney disease to name a few.

Our approach combines cutting edge electrophysiological methods such as voltage-clamp fluorimetry and single channel recordings with high‑resolution structural analysis such as x-ray crystallography. More recently, we have invested considerable effort to develop new single molecule fluorescence methods to study ligand dependent modulation of voltage-gated ion channels. Our research is constantly evolving but very broadly our research effort is directed towards these central questions.

1. How do ion channels sense temperature? What are molecular and structural determinants of temperature-sensing?

2. What are the mechanisms of voltage-gating? Despite overall conserved structure, why do some channels open when the membrane is hyperpolarized whereas others open upon depolarization?

3. What are the mechanisms of ligand-dependent activation in voltage-gated ion channels? How does a structurally symmetric ion channel exhibit both positive and negative cooperativity?

Selected Publications:

White, D.S., Goldschen-Ohm, M.P., Goldsmith, R.H., Chanda, B. Top-down machine learning approach for high-throughput single-molecule analysis eLife, April 8, 2020, DOI: 10.7554/eLife.53357

Kasimova, M.A., Tewari, D., Cowgill, J.B., Ursuleaz, W.C., Lin, J.L., Delemotte, L. and Chanda, B. Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating eLife, November 27, 2019, DOI: 10.7554/eLife.53400

Chen, H., Pan, J., Gandhi, D.M., Dockendorff,C., Cui, Q., Chanda, B., Henzler-Wildman,K.A. NMR structural analysis of isolated Shaker voltage-sensing domain in LPPG micelles, Biophysical Journal, June 25th, 2019, DOI: 10.1016/j.bpj.2019.0.20

White, D.S., Goldschen-Ohm, M.P., Goldsmith, R.H., Chanda, B. High-Throughput Single-Molecule Analysis via Divisive Segmentation and Clustering. bioRxiv, 603761 (2019).DOI: 10.1101/603761

Chowdhury, S., Chanda, B. Sodium channels caught in the act. Science, March 22, 2019, 363 (6433) 1278-1279, DOI: 10.1126/science.aaw8645

Cowgill, J., Klenchin, V.A., Alvarez-Baron, C.P., Tewari, D., Blair, A., Chanda, B.; Biploar switching by HCN voltage sensor underlies hyperpolarization activation, Proceedings of the National Academy of Sciences (USA), January 2018, 2019 116 (2) 670-678, DOI: 10.1073/pnas.1816724116

Last Updated: 5/18/2021 9:56:00 PM

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