What are the responsibilities and job description for the Postdoctoral Research Fellow – Ion Channel Ligand Screening & Discovery position at Washington University School of Medicine in St. Louis?

Postdoctoral Research Fellow – Ion Channel Small Molecule Screening & Discovery

Lab Overview

The Chamessian Laboratory at Washington University in St. Louis is dedicated to discovering novel ion channel modulators to treat pathologic pain. Our lab integrates neuroscience, pharmacology, and chemical biology in a highly collaborative environment, working closely with experts in medicinal chemistry and computational modeling. We are part of the Washington University Pain Center (WUPC) in the Department of Anesthesiology.

Position Description

We are seeking a highly motivated postdoctoral researcher to lead a project focused on developing and performing small molecule screening assays aimed at discovering novel ion channel-binding ligands for targeted protein degradation (TPD). The postdoc will be responsible for designing, optimizing, and implementing screening assays to identify compounds that modulate specific ion channel targets of interest. This includes establishing robust high-throughput workflows and assay protocols (e.g., fluorescence / voltage readouts, ligand-binding assays) to enable efficient screening of small-molecule libraries. This project builds on the exciting work described in our preprint Small molecule-mediated targeted protein degradation of voltage-gated sodium channels involved in pain (Chamessian et al 2025)

In addition, the successful candidate will utilize an automated patch clamp electrophysiology platform to characterize hits in detail. By applying automated patch clamp techniques, the postdoc will be able to rapidly assess the electrophysiological effects of candidate compounds on ion channel function, obtaining high-fidelity data on compound potency and mechanism. Hit compounds emerging from primary screens will then be progressed into secondary biological assays for validation. These include testing in heterologous cell lines expressing the ion channel target, as well as in human iPSC-derived sensory neurons to confirm efficacy in a physiologically relevant system. Through these studies, the postdoc will help advance the most promising hits toward lead compounds with therapeutic potential.

The postdoctoral fellow will be expected to take a leading role in this research project – from assay development and optimization, through high-throughput screening and data analysis, to hit validation and lead optimization. They will design experiments, interpret results, and troubleshoot technical challenges largely independently, while receiving guidance from the principal investigator and collaborating with the broader team. This is a full-time position (initially for 1 year with the possibility of extension) that offers an opportunity to make a significant impact in ion channel drug discovery. The postdoc will also be encouraged to contribute intellectually to project strategy. This project will offer the opportunity to engage in entrepreneurial and commercialization efforts to turn our research into real-world impact.

Primary Duties & Responsibilities

Develop and optimize screening assays : Design, develop, and refine small-molecule screening assays (in 96- or 384-well plate format) to discover ion channel ligands. This includes assay selection (fluorescence-based, luminescence, calcium influx, electrophysiological readouts, etc.), optimization of experimental conditions, and validation of assay robustness (e.g., Z' factor, signal-to-noise).
Implement automated patch clamp studies : Utilize an automated patch clamp (APC) system to conduct medium- to high-throughput electrophysiological recordings. Optimize APC protocols for the ion channel targets in question, perform compound screening on the APC platform, and analyze electrophysiological data to identify and characterize hit compounds’ effects on ion channel function.
High-throughput screening & analysis : Conduct high-throughput screening (HTS) campaigns using chemical libraries to identify hit compounds. This includes preparing reagents, managing compound libraries, running plate reader or APC experiments, and using software tools to analyze large datasets. Interpret screening results to select top candidate compounds for follow-up.
Hit validation in biological assays : Test and validate hit compounds in secondary biological assays . This will involve treating relevant cell lines (expressing the ion channel of interest) with hit compounds and measuring functional outcomes (e.g., ionic currents, calcium signaling, or reporter activity). Additionally, perform assays in iPSC-derived sensory neurons to evaluate compound efficacy in human neuron models, confirming target engagement and assessing potential off-target effects on neuronal function.
Lead refinement collaboration : Collaborate with medicinal chemists to discuss structure-activity relationships (SAR) and guide chemical optimization of lead compounds. Work with computational modelers as needed to understand binding interactions and refine compound design (if applicable). Incorporate feedback from these collaborators to prioritize compounds for next-round testing and development.
Data recording and dissemination : Maintain detailed experimental records of all procedures, protocols, and results in electronic lab notebooks. Analyze and compile data into figures and tables. Contribute to writing manuscripts for publication in peer-reviewed journals, and prepare abstracts, posters, or talks for scientific conferences. Ensure that results are communicated clearly to the team and broader community.
Teamwork and independent research : Work independently to drive the project forward on a day-to-day basis, demonstrating strong problem-solving skills and initiative. At the same time, actively collaborate with lab colleagues and external partners; participate in group meetings, share expertise, and help foster a positive, multidisciplinary team environment. Mentor junior lab members (e.g., graduate students or technicians) as opportunities arise, and contribute to the overall functioning and success of the lab’s research endeavors.

Required Qualifications

Education : Ph.D. (or equivalent doctoral degree) in neuroscience, pharmacology, molecular biology , biochemistry, or a related field. Candidates who have completed all requirements for the PhD and are awaiting graduation may also be considered.

Assay Development Expertise : Strong background in assay development and screening methodologies . Hands-on experience designing and optimizing biological or biochemical assays, preferably for drug / ligand screening purposes.

Cell-Based Screening Experience : Experience with plate-based assays and cell-based high-throughput screening. Proficiency in executing experiments in multi-well formats (96 / 384-well plates), using plate readers or imaging systems to collect assay readouts, and managing the technical aspects of screening large compound sets.

Analytical & Data Skills : Strong analytical skills with the ability to interpret large datasets from screening experiments. Experience with data analysis software (e.g., Excel, GraphPad Prism) and preferably some experience with programming or scripting (e.g., R or Python) for handling high-volume data.

Scientific Communication : Excellent scientific writing and communication skills. Demonstrated ability to write clear research reports or publications, and to effectively present data and conclusions in meetings or conferences. Fluent in discussing scientific concepts with both specialists and broader audiences.

Preferred Qualifications

Assay Development : Prior experience with developing, optimizing and performing biomolecular assays for drug discovery is highly desired.

Stem Cell Neuron Experience : Experience working with induced pluripotent stem cell (iPSC)-derived neurons , particularly sensory neurons or nociceptors. Hands-on expertise in culturing iPSC-derived cells and performing assays on neuronal cultures will be advantageous.

Electrophysiology Skills : Prior experience with automated patch clamp systems or other electrophysiological techniques (e.g., manual patch-clamp, multielectrode arrays). Familiarity with analyzing electrophysiological data and an understanding of ion channel biophysics is a strong plus.

Drug Discovery Knowledge : Knowledge of medicinal chemistry principles or experience working closely with chemists in a drug discovery setting. Familiarity with computational modeling or virtual screening for ligand discovery is a bonus.

Project Leadership : Demonstrated ability to lead research projects to completion, evidenced by independent project management, publications, or significant contributions to multi-disciplinary projects. Proven track record of effective collaboration across disciplines , showing aptitude to work with chemists, biologists, and data scientists as part of an integrated team.

Application Process

Interested candidates should apply by submitting the following documents :

Cover Letter : A brief cover letter describing your research background, relevant skills, and interest in this position. Please highlight how your experience aligns with the project and what you hope to achieve during the postdoctoral fellowship.

Curriculum Vitae (CV) : A detailed CV including your educational qualifications, research experience, technical skills, publications, and contact information for at least two references.

Research Summary (optional) : (If requested) A summary of past research accomplishments or a brief proposal of how you would approach the project.

References : Contact information (phone and email) for 2-3 academic or professional references who can speak to your qualifications and research experience. Alternatively, you may include letters of recommendation with your application if already available.

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Postdoctoral Research Fellow – Ion Channel Ligand Screening & Discovery

What are the responsibilities and job description for the Postdoctoral Research Fellow – Ion Channel Ligand Screening & Discovery position at Washington University School of Medicine in St. Louis?

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