Senior/Principal Scientist, Small Molecule Therapeutics
Cambridge, MA$148k - $208kfull-timePosted 3mo ago
About the role
Senior/Principal Scientist who leads early hit identification efforts using DNA-encoded libraries (DEL) and complementary screening technologies to discover and validate novel chemical matter, partnering with Chemistry, Computational, and Automation teams to build and scale a small molecule screening platform and drive hits through optimization.
Responsibilities
- Build and continuously improve DNA-encoded library (DEL) screening capabilities, tightly integrated with 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.
Qualifications
- 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.
- Demonstrated success designing, executing, and delivering impactful DNA-encoded library (DEL) screening campaigns, from selection strategy through validated hits that enable downstream chemistry.
- 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.
- Experience developing and optimizing biochemical and biophysical assays to triage, validate, and characterize screening hits, including assay quality metrics and troubleshooting.
- 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.
- 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.
- 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.
- Ability to establish and optimize activity assays to prioritize binding hits, probe mechanism of action, and guide follow-up experiments and medicinal chemistry decisions.
- Strong record of operating in interdisciplinary environments across chemistry, biology, automation, and computational teams, with excellent scientific communication and stakeholder alignment skills.
Skills
Required:DNA-Encoded Libraries (DEL) screeningHit identification and validationBiochemical & Biophysical assay developmentBiophysics techniques (SPR, BLI, DSF, ITC, MST, etc.)Automation & robotics in the labProtein construct design & collaborationCross-functional collaboration & communication
Benefits
- Full-time U.S. benefits package including medical, dental, and vision; employer-paid life and disability insurance; flexible time off with generous holidays; paid parental leave; educational assistance; commuter benefits; bike-share memberships; subsidized lunch program.
Last updated Jul 8, 2026. Interested? Apply on the company site.
About Lila Sciences
Pioneering Scientific Superintelligence
Pioneering Scientific Superintelligence to solve humankind’s greatest challenges.
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