Senior/Principal Scientist, Small Molecule Therapeutics

Your Impact at LILA

The Senior/Principal Scientist, Small Molecule Therapeutics will lead early hit identification efforts, leveraging their expertise in DNA-encoded libraries (DEL) and complementary screening technologies to discover and validate novel chemical matter.  This role will partner cross-functionally with Lila’s Chemistry, Computational, and Automation teams to develop and scale a best-in-class small molecule screening platform.  The Senior/Principal Scientist will also drive the progression of hits through optimized biochemical and biophysical assay cascades, while identifying and securing fit-for-purpose protein sources to enable robust characterization and follow-up.  

What You'll Be Building

• Build and continuously improve DNA-encoded library (DEL) screening capabilities, tightly integrated with Lila’s AI-enabled chemistry design engine and automated/robotic synthesis platform.
• Design and execute DEL screening campaigns, including selection strategy, experimental execution, data interpretation, and translation into robust hit validation and hit-to-lead workflows.
• Develop, optimize, and run fit-for-purpose biochemical and biophysical assays to validate and characterize hits emerging from Lila’s screening platform.
• Evaluate, implement, and operationalize complementary screening modalities (e.g., fragment, affinity-based, functional, and other relevant approaches) to expand hit-finding coverage and diversify chemotypes.
• Establish and manage collaborations (internal and external) to secure high-quality protein supply suitable for high-throughput screening and assay development.
• Define, produce, and triage optimal protein constructs (including construct design and quality criteria) to enable reliable screening performance and confident downstream hit validation.

What You'll Need to Succeed

• Education & experience: PhD in Biology, Chemical Biology, Biochemistry, or a related field with 6–8 years of relevant drug discovery experience; or MS/BS with 10+ years of industry experience in small molecule discovery, screening, and hit finding.
• DEL expertise: demonstrated success designing, executing, and delivering impactful DNA-encoded library (DEL) screening campaigns, from selection strategy through validated hits that enable downstream chemistry.
• Hit identification breadth: strong working knowledge of complementary screening approaches (e.g., fragment-based, affinity-based, functional/phenotypic, and other relevant modalities) to diversify hit sources and chemotypes.
• Assay development & validation: experience developing and optimizing biochemical and biophysical assays to triage, validate, and characterize screening hits, including assay quality metrics and troubleshooting.
• Biophysics proficiency: hands-on experience with affinity/biophysics methods used in hit confirmation and ranking (e.g., SPR, BLI, DSF, ITC, MST, or comparable techniques), with the ability to interpret data critically.
• Automation-forward mindset: experience operating in automation- and robotics-enabled labs, including liquid handling integration, assay automation, and designing scalable, reproducible experimental workflows.
• Protein partnership: proven ability to collaborate closely with protein science collaborators to enable screening, spanning construct strategy, expression system selection, purification requirements, and quality criteria for assay readiness.
• Comprehensive hit-to-lead understanding: clear understanding of the full hit identification and validation funnel, including orthogonal confirmation, selectivity/counterscreens, artifact mitigation, and translation into hit-to-lead-enabling data packages.
• Mechanism-driven assay design: ability to establish and optimize activity assays to prioritize binding hits, probe mechanism of action, and guide follow-up experiments and medicinal chemistry decisions.
• Cross-functional effectiveness: strong record of operating in highly interdisciplinary environments across chemistry, biology, automation, and computational teams, with excellent scientific communication and stakeholder alignment skills.

Bonus Points For

• Deep expertise in large-scale screening approaches, including DNA-encoded libraries (DEL), fragment-based screening, and other contemporary small molecule discovery technologies.
• Strong command of screening data analysis, interpretation, and stewardship of large experimental datasets (including clear data QC, hit calling, and prioritization frameworks).
• Hands-on experience across multiple biophysical modalities (e.g., SPR, BLI, DSF, MST, ITC, MS-based methods) and the ability to select fit-for-purpose methods for confirmation and ranking.
• Extensive understanding of biochemical activity assays, including development, optimization, and interpretation across common readouts (luminescent, colorimetric, fluorometric, and label-free formats).
• Experience designing, producing, and evaluating protein constructs that enable robust, scalable high-throughput screening and downstream validation.
• Familiarity operating in AI-enabled drug discovery environments and/or integrating machine learning outputs into experimental design, prioritization, and iterative learning cycles.
• Experience building screening capabilities end-to-end, including instrumentation evaluation/selection, workflow design, and lab automation implementation.
• Ability to thrive in a fast-paced, highly innovative environment.
• Excellent communication skills, with the ability to synthesize and explain complex datasets to diverse audiences across chemistry, biology, automation, and computational teams.