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Goldschen-Ohm Lab

Ion Channels • Biophsycial Mechanisms • Disease Variants • Drugs and Therapeutics
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Department of Neuroscience
Open-state dynamics and allosteric modulation of the α1β3γ2 GABAA receptor stabilized by L9'T/S substitutions
Molecular dynamics simulation of asymmetric pore closure.
A single main-chain hydrogen bond required to keep GABAA receptors closed
A single H-bond keeps GABAA receptors closed
Bioelectricity and Molecular Signaling in honor of Richard Aldrich
Special issue of Biophysical Journal 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
Goldschen-Ohm Lab Photo 2025

News

2026
  • Cecilia Borghese presents her discovery of an ancient hydrogen bond essential to inhibitory neurotransmission at the Ion Channels Gordon Research Conference.
  • Netrang Desai was invited for a summer research internship at Pfizer.
  • Cecilia Borghese and coworkers discover an ancient hydrogen bond essential to inhibitory neurotransmission. Read about it on bioRxiv.
  • Tapas Haldar and coworkers resolve single-molecule binding dynamics to a CNG channel in nanophotonic waveguides. Read about it on bioRxiv.
  • Draegan Watson and coworkers investigate the functional consequence of a GABAA receptor α subunit variant of unknown significance found in an individual with epilepsy. Read about it in microPublication.
  • Netrang Desai and coworkers investigate the functional significance of a conserved proline in the M2-M3 linker of GABAA receptors found only in β subunits. Read about it on bioRxiv.
  • In a collaboration between the labs of Senthil Natesan and Marcel Goldschen-Ohm, Ayobami Diyaolu and Cecilia Borghese combine to study spontaneously active GABAA receptor mutants both in cells and in silico. Accelerated molecular dynamics simulations of mutants show open-like conformations paralleling electrophysiological measures, and docking of an antagonist induces bottom-up asymmetric pore closure. These simulations provide atomistic insight into the open-closed conformational transition. Read about it on bioRxiv and now peer-reviewed in Journal of Chemical Information and Modeling.
  • A new undergraduate student Arjun Rajagopal joins the lab. Welcome Arjun!
2025
  • Marcel Goldschen-Ohm was elected to the Society of General Physiologists council.
  • Marcel Goldschen-Ohm and Blair Johnson were awarded an APX grant from the University of Texas at Austin to develop an automated patch clamp combining custom fluidics with common electrophysiology equipment to enable rapid ion channel variant diagnosis and drug screening at low cost for individual research labs.
  • Marcel Goldschen-Ohm and Andres Jara-Oseguera were awarded a Catalyst 2.0 grant from the University of Texas at Austin College of Natural Sciences to lay the foundation for a new collaborative project designed to screen every possible single residue variant in a synpatic GABAA receptor with a high throughput unbiased approach involving fluorescence detection of channel activity and next generation sequencing.
  • Cecilia Borghese and coworkers uncover a new part of the activation mechanism coupling binding to gating in GABAA receptors that involves backbone hydrogen bonding resistant to genetic mutation. Read about it in Nature Communications. This work was a collaboration with Jason Galpin and Chris Ahern from the University of Iowa and Samuel Eriksson Lidbrink, Reba Howard, and Erik Lindahl from Stockholm University.
  • Darren Lopez recieves an Outstanding Teaching Assistant Award for his phenomenal job as an undergraduate teaching assistant in Marcel Goldschen-Ohm's course Programming and Data Analysis for Modern Neuroscience.
  • Khadeeja Shah wins an award for her outstanding poster presentation of her research at the Technology & Science Undergraduate Research Forum.
  • Netrang Desai was awarded an Undergraduate Summer Training Fellowship for his project on GABAA receptor structure-function.
  • Marcel Goldschen-Ohm has been promoted to Associate Professor with Tenure.
  • Marcel Goldschen-Ohm presents the lab's latest work in a special symposium "Best of Biophysics" at the Biophysical Society annual meeting.
  • Our recent paper was selected as the Paper of the Year by the Biophysical Journal and Biophysical Society which annually recognizes a single outstanding paper from an early career investigator. For this award, Marcel Goldschen-Ohm was invited to speak in the Best of Biophysical Journal symposium at the Biophysical Society annual meeting.
2024
  • Cecilia Borghese and coworkers uncover a new part of the activation mechanism coupling binding to gating in GABAA receptors that involves backbone hydrogen bonding resistant to genetic mutation. Read about it in bioRxiv.
  • Marcel hosts Jorge Contreras for the department of Neuroscience seminar series at the University of Texas at Austin.
  • Marcel hosts Chen Zhao for the department of Neuroscience seminar series at the University of Texas at Austin.
  • A new undergraduate student Khadeeja Shah joins the lab. Welcome Khadeeja!
  • Netrang Desai was awarded an Undergraduate Research Fellowship for his project on GABAA receptor structure-function.
  • 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.
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.
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 nature's transistors/transducers in biological circuits. They are essential for rapid signaling between neurons and other excitable cells throughout the body, and are major drug targets for treating aberrant behavior associated with human disorders. An overarching goal of the Goldschen-Ohm lab is to understand the molecular mechanisms by which channels operate and the physical basis by which small molecule binding regulates their activity.

We have a long-standing interest in pentameric ligand-gated ion channels (pLGICs) such as the GABAA receptor, which is the major inhibitory neurotransmitter receptor in the mammalian central nervous system. We are currently focused on addressing major gaps in both biophysics and personalized medicine including:

  1. Resolving the paradox of why gain-of-function (GOF) variants in GABAA receptors are associated with epilepsy, a disorder of hyperexcitability, when GOF variants should naively reduce excitability.
  2. Uncovering the contribution of backbone hydrogen bonding (H-bonding) to channel gating and drug modulation. Very little is known about backbone interactions in pLGICS, likely due to the fact that these interactions cannot be directly probed with conventional mutagenesis which does not alter the chemistry of the backbone. Using unnatural amino acids, we have recently discovered that backbone H-bonds within gating loops are essential for GABAA and Glycine receptor activation by neurotransmitters. Furthermore, we have show that disruption of one of these H-bonds can explain pathogenic variants linked to epilepsy, neurodevelopmental disorders including intellectual disability, and hyperekplexia (startle disease). Read about it on bioRxiv. These findings suggest that backbone H-bonds within gating loops are a largely unexplored area for highly specific drug modulation.
  3. Developing new approaches for high-throughput screening of variants and drugs to enable realistic personalized medicine. We currently collaborate with clinicians where we help to functionally characterize variants of unknown significance found in individuals with disorders such as epilepsy. However, conventional approaches are limited in their ability to screen large numbers of variants and drugs. We are currently collaborating to develop new approaches enabling high-throughput screening of variants and drugs to realize true personalized medicine at scale.
  4. Disecting the molecular mechanisms underlying the asymmetric functional contributions of subunits in heteromeric pLGICs. We have recently discovered that the M2-M3 linkers, which are essential for coupling neurotransmitter binding to channel gating, have highly asymmetric functional contributions in GABAA receptors. Read about it in Biophysical Journal.

Ion channels are natures transistors/transducers

Cell Attached Single Channel

Single-molecule fluorescence imaging

Lasers Overlay

Software

  • xarray-graph: PyQt UIs for Xarray DataTree including tree view and DataArray slice graphing and processing. This aims to be a complete signal processing and visualization tool for 1-D slices of N-dimensional array data as is common in many scientific domains such as electrophysiology (i.e., time series recordings).
  • 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.
  • 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).

Resources

Publications

2026

2025

2024

2023

2022

2021

2020

2019

Prior Publications

2017

2016

2015

2014

2013

2011

2010