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Goldschen-Ohm Lab

Ion Channels • Single-Molecule Spectroscopy • Dynamics
Bioelectricity and Molecular Signaling in honor of Richard Aldrich
Bioelectricity and Molecular Signaling in honor of Richard Aldrich
M2-M3 linkers
Subunit-specific roles for M2-M3 linkers
State-dependent potentiator
State-dependent energetics of allosteric potentiators
OTOP Zinc gating
Zinc gating of OTOP sour taste receptors
GABA & DZ sites
Benzodiazepines: A Mechanistic Perspective
Ligand Depletion
The surprising difficulty of "simple" equilibrium binding measurements
smBEVO Trace
smBEVO: A computer vision approach to single-molecule drift correction
TAX4 Nanovesicle
Single-molecule ligand binding to CNG channels in nanovesicles
svm Boundary
AutoDISC: Automated single-molecule idealization
M23 Linker
Benzodiazepine drug mechanisms

News

2024
  • Marcel Goldschen-Ohm was selected to receive a 2024 College of Natural Sciences Teaching Excellence Award for his outstanding teaching in the Department of Neuroscience at the University of Texas at Austin.
  • Marcel Goldschen-Ohm presents Cecilia Borghese's work on backbone hydrogen bonding in GABAA receptor activation at the Ion Channels Gordon Research Conference. This work was a collaboration with Jason Galpin and Chris Ahern from the University of Iowa and Samuel Lidbrink, Reba Howard, and Erik Lindahl from Stockholm University.
  • Marcel Goldschen-Ohm and Baron Chanda wrote an editorial for the special issue Bioelectricity and Molecular Signaling in honor of Richard Aldrich. Read about it in Biophysical Journal
  • Zachary Endres and Joseph (Wagner) Nors show that the central hydrophobic residues in GABAA receptor M2-M3 linkers have highly asymmetric subunit-specific roles in gating and drug modulation. Read about it in Biophysical Journal
  • Cecilia Borghese and Marcel Goldschen-Ohm discuss a new and notable article on the energetics of GABAA receptor allosteric potentiators. Read about it in Biophysical Journal
  • Cecilia Borghese presents her work on backbone hydrogen bonding in GABAA receptor activation at the Biophysical Society 2024 annual meeting.
  • New undergraduate students Rohith Gajjala, Vignesh Sadasivan, and Vineeth Murugan join the lab. Welcome Rohith, Vignesh, and Vineeth!
2023
  • A new undergraduate student Netrang Desai joins the lab. Welcome Netrang!
  • A new postdoc Tapas Haldar joins the lab. Welcome Tapas!
  • Marcel Goldschen-Ohm was invited to speak at the Sophion Bioscience Ion Channel Modulation Symposium in Irvine, CA on October 18-19 2023.
  • Marcel Goldschen-Ohm serves as editor for a special issue in Biophysical Journal honoring the scientific contributions of Richard Aldrich: Bioelectricity and Molecular Signaling.
  • A new graduate student Myles Joyce rotates in the lab. Welcome Myles!
  • A new research scientist Cecilia Borghese joins the lab. Welcome Cecilia!
  • In collaboration with Emily Liman we investigate gating of OTOP sour tast receptors by Zinc. Read about it in eLife
  • Marcel Goldschen-Ohm's review of the molecular mechanisms of benzodiazepines was chosen as an Editor's Choice Article in the journal Biomolecules for its high quality and high amount of downloads.
  • Marcel Goldschen-Ohm gives invited seminar at the University of Iowa Deparment of Molecular Physiology & Biophysics.
  • Marcel Goldschen-Ohm invited to speak at the Biophysical Society 2023 annual meeting workshop on high-throughput single-molecule spectroscopy.
  • A new postdoc Zubayer Ibne Ferdous joins the lab. Welcome Zubayer!
2022
  • The lab was awarded an R01 from the NIH.
  • The lab was awarded an R03 from the NIH.
  • Marcel Goldschen-Ohm reviews molecular mechanisms of benzodiazepines, one of the most widely prescribed class of psycotropic drugs today. Read about it in Biomolecules.
  • Marcel Goldschen-Ohm joins the editorial board at Frontiers in Pharmacology.
  • Marcel Goldschen-Ohm joins the steering group at Biophysics Colab.
  • Started a new collaboration with Dr. Susanne Ressl that I'm super excited about!
  • Thomas Middendorf and Marcel Goldschen-Ohm discuss a new article from Godellas and Grosman about the surprising difficulty of equilibrium binding measurements for ligand-gated ion channels. Read about it in the Journal of General Physiology.
  • Argha Bandyopadhyay awarded the prestigious honor of becoming a Deans Honored Graduate, a distinction only given to a few of the very top students at the University.
  • Marcel Goldschen-Ohm May 5th seminar for UT Biochemistry.
  • Marcel Goldschen-Ohm invited to speak at the Ion Channels 2022 Gordon Research Conference.
  • Joseph (Wagner) Nors presents his work on drug modulation in GABAA receptors in a platform presentation at the Biophysical Society 2022 annual meeting. Vishal Patel and Argha Bandyopadhyay also give poster presentations of their work at the meeting.
2021
  • Khue Tran and Argha Bandyopadhyay develop smBEVO which leverages computer vision algorithms for best in class baseline drift correction in single-molecule time series. Read about it on bioRxiv
  • Vishal Patel, Mohamed Salinas, Darong Qi and coworkers use cell-derived nanovesicles and single-molecule optical tracking of individual ligand binding events to show that cyclic nucleotide binding in a CNG channel is followed by a conformational change of the binding domain(s) that preceeds pore opening. These observations also reveal that binding of the second of four cyclic nucleotides is either independent of the first or at most a weakly positive cooperative process. Read about it in Nature Communications and also check out the Biophysics Colab peer reviews
  • Argha Bandyopadhyay spearheads development of AutoDISC which optimizes DISC for completely automated model-free idealization of single-molecule time series with state-of-the-art accuracy and performance. Read about it in Biophysical Journal and download AutoDISC for MATLAB
  • Khue Tran recieves TIDES fellowship for summer research.
  • Joseph (Wagner) Nors and coworkers identify a critical residue mediating coupling between the benzodiazepine drug site and the channel pore in a neurotransmitter-gated GABAA receptor. Read about it in eLife
  • Argha Bandyopadhyay presents a video and poster at the Capital of Texas Undergraduate Research Conference about his work on a novel algorithm for automated single-molecule time series analysis. Watch the video
2020
  • Marcel Goldschen-Ohm joins the board of reviewing editors at eLife.
  • Joseph (Wagner) Nors presents a poster at the Biophysical Society annual meeting about his work on coupling between the benzodiazepine binding site and channel pore in GABAA receptors.
  • Argha Bandyopadhyay presents a poster at the American Physician Scientists Association (APSA) conference about his work on a novel algorithm for automated single-molecule time series analysis.
  • David White spearheads developement of DISC for model-free idealization of single-molecule time series with state-of-the-art accuracy and performance. Read about it in eLife
2019

Research

Ion channels are critical for rapid signaling between neurons and other excitable cells throughout the body. Drug binding to specific recognition sites allows tuning channel behavior to treat aberrant behavior associated with human disorders. An overarching goal of the lab is to understand the molecular mechanisms by which channels operate and the physical basis by which small molecule ligand/drug binding regulates their activity. Understanding these mechanisms will provide a necessary framework for rational development of novel therapeutic strategies to improve treatments that impact human health.

The lab utilizes a variety of approaches such as fluorescence spectroscopy, electrophysiology and biochemistry at both single-molecule and ensemble levels to probe the dynamic motions of proteins that underlie their biological function. As part of this process, we are also interested in developing new approaches or workflows to resolve the molecular forces and interactions involved in drug binding and modulation.


Ion channels are natures transistors/transducers.

Cell Attached Single Channel

Single-molecule fluorescence imaging.

Lasers Overlay

  • Cell-derived nanovesicles for single-molecule fluorescence
  • Single-molecule ligand binding dynamics
  • FRET-based approaches to probe conformational dynamics
  • Unnatrual Amino Acids
  • Click Chemistry for site-specific fluorescence
  • Cryo-EM structural analysis of ion channels

People

Marcel Goldschen-Ohm
Marcel Goldschen-Ohm, PhD, Assistant Professor
goldschen-ohm@utexas.edu  •  GitHub  •  LinkedIn
Cecilia Borghese
Cecilia Borghese, PhD
Tapas Haldar
Tapas Haldar, PhD
Pranavi Garlapati
Pranavi Garlapati
Netrang Desai
Netrang Desai
Rohith Gajjala
Rohith Gajjala
Vignesh Sadasivan
Vignesh Sadasivan
Vineeth Murugan
Vineeth Murugan


Past Lab Members

Zachary Endres
Zachary Endres, BS
UT Austin Deans Honored Graduate
Applying to medical school
Joseph Wagner
Joseph (Wagner) Nors, BS
Joined the Molecular and Cellular Physiology PhD program at Stanford
Argha Bandyopadhyay
Argha Bandyopadhyay, BS
UT Austin Deans Honored Graduate
Joined the MD/PhD program at NYU Langone
Shipra Gupta
Shipra Gupta, PhD
Joined Lawrence Berkeley National Laboratory
Vishal Patel
Vishal Patel, BS
Joined the MD program at Dell Medical School at the University of Texas at Austin
Khue Tran
Khue Tran, BS
Joined the Neurobiology and Behavior PhD program at Stony Brook University

Software

  • napari-cosmos-ts: Napari plugin for colocalization single-molecule spectroscopy (CoSMoS) time series (TS) analysis. Find molecules and extract and visualize their one-dimensional time series.
  • xarray-graph: GUI for visualizing and analyzing one-dimensional time series slices from a tree of xarray datasets. Includes regions, measurement, curve fitting, and more.
  • pyDISC: GUI for idealizing one-dimensional time series using the DIvisive Segmentation and Clustering (DISC) algorithm plus tools for adjusting number of levels or generic HMM optimizaiton. An excellent tool for idealizing time series, tested primarily on fluorescence data. In many cases automated idealization is very good, but otherwise manual refinement by adding/removing levels and/or HMM optimization does the trick.
  • AutoDISC: MATLAB UI extending the DIvisive Segmentation and Clustering (DISC) algorithm for completely automated model-free idealization of single-molecule piecewise constant time series in the presence of per-molecule variability as often observed in high-throughput fluorescence imaging paradigms such as TIRF. Read about it in Biophysical Journal
  • smBEVO: Single-molecule time series baseline estimation via visual optimization. smBEVO leverages computer vision algorithms for best in class baseline drift correction in single-molecule time series. Read about it on bioRxiv
  • Kinetic Model Builder: HMM model building and optimization GUI for patch-clamp electrophysiology (or other time series) data. MacOSX only.
  • EigenLab: C++ utility for parsing/evaluating matrix math equations input at run time in a format similar to MATLAB (requires Eigen for matrix math).

  • single-molecule-imaging-toolbox: A suite of programs for single-molecule image analysis in MATLAB.
  • PlotXRegionsUITool: MATLAB tool for interactive plot x-axis region selection and analysis/manipulation of plotted data based on selected regions. Supports plotBig_Matlab for fast plotting of large data traces (e.g. single channel records).
  • PatchMeister: MATLAB graphical user interface for electrophysiology (or other time series) analysis. Note, in the future PlotXRegionsUITool will either supercede or merge with this package.

Resources

  • bioRENDER: Images and clip art for biology.

Publications

2024

2023

2022

2021

2020

2019


Prior Publications

2017

2016

2015

2014

2013

2011

2010