Associate Scientist I, Biochemistry

Pliant Therapeutics; South San Francisco (CA); On-site; USD 125,000 - 138,000; Full time

Job summary

Pliant Therapeutics in South San Francisco is seeking an Associate Scientist I to develop, optimize, and run biochemical binding assays (AlphaScreen/AlphaLISA) for medium- to high-throughput screening, generating potency and selectivity data to guide medicinal chemistry decisions.

This hands-on role reports to the Senior Vice President, Research and requires expertise in assay development, screening formats, and data analysis, with a focus on robust signal windows and reproducibility.

Qualifications

• BS in Biochemistry/ Biology/ Chemistry with 7+ years in pharma, or MS with 5+ years.
• Hands-on AlphaScreen/AlphaLISA assay development and troubleshooting.
• Experience in 384- and 1536-well HTS formats.
• Proficiency with liquid handling and plate readers for Alpha detection.
• Familiarity with high-content imaging (Operetta CLS).
• Strong data analysis and curve-fitting skills.
• Excellent ELN documentation and independent collaboration.

Responsibilities

• Design, develop and optimize biochemical binding assays, with a focus on AlphaScreen/AlphaLISA proximity formats (e.g., protein–protein and protein–ligand interaction and competition assays).
• Miniaturize and transfer assays to 384- and 1536-well formats; validate them for screening using Z′, signal-to-background, CV and reference‑compound reproducibility.
• Support cell-based assays, including mammalian cell culture, plating and compound treatment, cell density and workflow optimization, acquire and analyze images on high-content imaging systems.
• Execute medium-to high-throughput screening campaigns and dose-response (IC50/EC50) profiling to support hit identification and SAR.
• Identify and triage assay interference using counter-screens and orthogonal formats.
• Manage compound and sample workflows, including plate preparation and retrieval from automated sample storage systems.
• Analyze, QC and report data in Scilligence; maintain complete, contemporaneous ELN records.
• Write and maintain SOPs and assay reports; present results and issues clearly at project team meetings.
• Qualify critical reagents (proteins, antibodies, tagged constructs) in partnership with protein sciences.

Skills

AlphaScreen/AlphaLISA

HTRF/TR-FRET

Data analysis

Cell culture

Automation scripting

Education

BS in Biochemistry/ Biology/ Chemistry

MS with 5+ years

Tools

i5 BIOMEK

Tempest

EnVision

PHERAstar

Operetta CLS

GraphPad Prism

Genedata Screener

KNIME

Python

R

Job description

At Pliant, we believe differentiated science can make a meaningful impact. We see our success as a direct result of the central role that each team member plays in advancing our mission to develop therapies that target the disease at its source. We are seeking creative, curious and collaborative individuals who dare to succeed, are committed to making an important impact on patient’s lives and will help us build one Pliant!

Description

We are seeking an Associate Scientist I to develop, optimize and run biochemical binding assays that screen compounds in medium- to high-throughput format. You will own AlphaScreen/AlphaLISA assays from reagent qualification through routine screening, generating the potency and selectivity data that drive our medicinal chemistry decisions. This is a hands-on laboratory role reporting to Senior Vice President, Research based in South San Francisco.

Responsibilities

• Design, develop and optimize biochemical binding assays, with a focus on AlphaScreen/AlphaLISA proximity formats (e.g., protein–protein and protein–ligand interaction and competition assays).
• Optimize assay conditions — bead and reagent titrations, cross‑titration of binding partners, buffer, DMSO tolerance, incubation time and light/temperature sensitivity — to deliver robust signal windows.
• Support cell-based assays, including mammalian cell culture, plating and compound treatment, cell density and workflow optimization, acquire and analyze images on high-content imaging systems.
• Miniaturize and transfer assays to 384- and 1536-well formats; 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 SAR.
• Identify and triage assay interference (e.g., singlet-oxygen quenchers, color quenchers, biotin mimetics, metal chelators) using counter-screens and orthogonal formats.
• Manage compound and sample workflows, including plate preparation and retrieval from automated sample storage systems.
• Analyze, QC and report data in Scilligence; maintain complete, contemporaneous ELN records.
• Write and maintain SOPs and assay reports; present results and issues clearly at project team meetings.
• Qualify critical reagents (proteins, antibodies, tagged constructs) in partnership with protein sciences, and track lot-to-lot performance.

Qualifications

To perform this job successfully, an individual must be able to perform each essential duty. The requirements listed below are representative of the knowledge, skill, abilities, and prior experience required.

• BS in Biochemistry, Biology, Chemistry or a related field with 7+ years of relevant biopharmaceutical industry experience, or an MS with 5+ years.
• Direct, hands‑on experience developing and running AlphaScreen and/or AlphaLISA assays, including troubleshooting signal window, hook effect and compound interference.
• Demonstrated track record of 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 (e.g., i5 BIOMEK, Tempest or similar) and multimode plate readers capable of Alpha detection (e.g., EnVision, PHERAstar).
• Familiarity with high-content imaging equipment such as the Operetta CLS.
• Sound understanding of binding kinetics and pharmacology: Kd, Ki, IC50, Cheng–Prusoff, and the assumptions behind them.
• Strong data analysis skills, including curve fitting and assay statistics (e.g., GraphPad Prism, Genedata Screener or equivalent).
• Excellent documentation practices in an electronic lab notebook.
• Experience with cell culture and cell‑based assays supporting drug screening.
• Strong attention to detail and scientific rigor, including catching data‑quality issues early and questioning unexpected results before reporting them.
• Proactive, transparent communicator who works independently day to day while collaborating closely with chemistry and biology teams.

Required Qualifications

• Experience operating and maintaining automated compound/sample storage systems (e.g., Brooks/Azenta, Hamilton Storage, or similar), including inventory management, cherry-picking and plate reformatting.
• Experience with orthogonal binding and proximity formats — 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 (e.g., Python, R, or KNIME).

The annual base salary for this role is $125K – $138K. Individual pay may vary based on additional factors, including, and without limitation job‑related skills, experience, work location and relevant education or training. Pliant’s compensation package also includes benefits, equity, and annual target bonus for fulltime positions.

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