Associate Scientist I, Biochemistry

Pliant Therapeutics, Inc.•South San Francisco, CA

2d•$125,000 - $138,000•Onsite

About The Position

Pliant is seeking an Associate Scientist I to develop, optimize, and run biochemical binding assays for medium- to high-throughput compound screening. The role owns AlphaScreen/AlphaLISA assays from reagent qualification through routine screening and generates potency and selectivity data to guide medicinal chemistry decisions. It is a hands-on laboratory position based in South San Francisco and reports to the Senior Vice President, Research.

Requirements

Bachelor’s degree in Biochemistry, Biology, Chemistry, or a related field and 7+ years of relevant biopharmaceutical industry experience, or a master’s degree and 5+ years of relevant experience.
Direct hands-on experience developing and running AlphaScreen and/or AlphaLISA assays, including troubleshooting signal windows, hook effect, and compound interference.
Demonstrated experience developing and validating biochemical binding assays for medium- to high-throughput screening in 384- and/or 1536-well formats.
Proficiency with liquid handlers and plate-based workflows, such as i5 BIOMEK, Tempest, or similar, and multimode plate readers capable of Alpha detection, such as EnVision or PHERAstar.
Familiarity with high-content imaging equipment such as the Operetta CLS.
Sound understanding of binding kinetics and pharmacology, including Kd, Ki, IC50, Cheng–Prusoff, and their underlying assumptions.
Strong data analysis skills, including curve fitting and assay statistics, using tools such as GraphPad Prism, Genedata Screener, or equivalent.
Excellent electronic lab notebook documentation practices.
Experience with cell culture and cell-based assays supporting drug screening.
Strong attention to detail and scientific rigor, including identifying data-quality issues and questioning unexpected results before reporting.
Proactive and transparent communication skills, with the ability to work independently day to day and collaborate closely with chemistry and biology teams.
Experience operating and maintaining automated compound/sample storage systems, including inventory management, cherry-picking, and plate reformatting.
Experience with orthogonal binding and proximity formats such as HTRF/TR-FRET, fluorescence polarization, SPR, or BLI for hit confirmation.
Experience with integrated robotic screening systems and scheduling software.
Experience screening against integrins, other cell-surface receptors, or protein–protein interaction targets.
Scripting or automation skills for data processing, such as Python, R, or KNIME.

Responsibilities

Design, develop, and optimize biochemical binding assays, particularly AlphaScreen/AlphaLISA proximity assays for protein–protein and protein–ligand interactions and competition.
Optimize assay conditions, including bead and reagent titrations, binding-partner cross-titrations, buffer, DMSO tolerance, incubation time, and light and temperature sensitivity.
Support cell-based assays, including mammalian cell culture, plating, compound treatment, cell-density and workflow optimization, and image acquisition and analysis using high-content imaging systems.
Miniaturize and transfer assays to 384- and 1536-well formats and validate them for screening using Z′, signal-to-background, CV, and reference-compound reproducibility.
Execute medium- to high-throughput screening campaigns and dose-response (IC50/EC50) profiling to support hit identification and structure–activity relationship (SAR) work.
Identify and triage assay interference, including singlet-oxygen quenchers, color quenchers, biotin mimetics, and metal chelators, using counter-screens and orthogonal formats.
Manage compound and sample workflows, including plate preparation and retrieval from automated sample storage systems.
Analyze, quality-check, and report data in Scilligence, and maintain complete, contemporaneous electronic lab notebook records.
Write and maintain standard operating procedures and assay reports; clearly present results and issues at project team meetings.
Qualify critical reagents, including proteins, antibodies, and tagged constructs, in partnership with protein sciences, and track lot-to-lot performance.