Principal / Senior Principal Scientist, Small Molecule Therapeutics

About the role

Lila Sciences is seeking a Senior Principal Scientist, Small Molecule Therapeutics to define and execute the protein science and structural biology strategy that underpins small molecule therapeutic discovery. The successful hire will own the end-to-end management of recombinant protein construct design, engineering, expression, purification, and structural biology workflows that directly enable screening, hit validation, and structure-guided optimization across the platform. This role requires strategic oversight of external partnerships and internal capability building while maintaining deep, hands-on engagement in experimental design, data interpretation, and cross-functional decision-making. The position holder will act as the central point of expertise for ensuring that high-quality, functionally validated protein reagents are delivered on time to unblock chemistry, assay biology, and structural teams. Close collaboration with screening, assay development, computational chemistry, and medicinal chemistry will define how protein science de-risks target tractability and enables efficient compound progression. The individual will also own the roadmap for progressively bringing key expression and purification capabilities in-house while establishing rigorous quality standards for all protein reagents. Ultimately, this role shapes the structural biology output that determines whether programs advance with high-confidence mechanistic insights and optimized chemical starting points.

Key facts

What you'll do

Lead the protein science strategy for small molecule programs, ensuring timely delivery of high-quality protein reagents for screening, assay development, biophysics, crystallography, Cryo-EM, and downstream validation.

Oversee recombinant protein expression and purification efforts across external partners and CROs, including vendor selection, scope definition, protocol review, troubleshooting, quality assessment, and timeline management.

Develop and execute a roadmap to bring recombinant protein expression and purification capabilities in-house over time, including recommendations on infrastructure, workflows, staffing, instrumentation, and quality standards.

Lead construct design and protein engineering efforts to enable soluble, stable, active, and structurally tractable protein reagents across diverse target classes.

Design construct strategies including domain boundaries, truncations, tags, mutations, fusion partners, stabilizing variants, ortholog selection, and expression system selection.

Partner with assay biology, screening, chemistry, computational chemistry, and translational teams to ensure protein reagents are fit-for-purpose for biochemical, biophysical, cellular, and structural applications.

Lead outsourced X-ray crystallography activities, including construct and ligand complex strategy, crystallization campaign design, CRO management, structure review, and integration of structural insights into medicinal chemistry.

Manage external Cryo-EM activities where appropriate, including feasibility assessment, sample preparation strategy, vendor coordination, and interpretation of structural results.

Establish quality-control expectations for protein reagents, including purity, identity, activity, stability, aggregation state, binding competence, post-translational modifications, and lot-to-lot consistency.

Troubleshoot protein production, purification, stability, and structural biology challenges in collaboration with internal teams and external partners.

Build scalable processes for managing external protein science and structural biology work, including statements of work, decision criteria, data packages, documentation, and knowledge transfer.

Serve as a subject-matter expert in protein expression, purification, construct engineering, X-ray crystallography, and structural biology across the small molecule therapeutics portfolio.

Contribute to target assessment and program strategy by evaluating protein tractability, reagent feasibility, structural enablement, and risk mitigation plans.

Mentor and develop future team members as internal protein science capabilities expand.

Maintain awareness of emerging technologies, vendors, platforms, and best practices in recombinant protein production, structural biology, and structure-enabled drug discovery.

Requirements

PhD in biochemistry, structural biology, molecular biology, protein engineering, or a related discipline, with 10+ years of relevant drug discovery experience; or an MS/BS with 15+ years of industry experience focused on protein chemistry and structural biology.

Deep expertise in recombinant protein expression and purification across multiple expression systems, such as bacterial, insect, and mammalian systems.

Demonstrated experience designing and engineering protein constructs for biochemical assays, biophysical characterization, crystallography, and/or Cryo-EM.

Strong track record supporting small molecule drug discovery programs, including hit identification, hit-to-lead, and lead optimization through protein-based approaches.

Proven ability to manage external vendors and CRO relationships, including negotiation, scope definition, timeline management, and quality oversight.

Experience establishing and maintaining quality control frameworks for protein reagents, including activity assays, stability studies, and lot release criteria.

Thorough understanding of protein expression challenges across diverse target classes and strategies to overcome solubility, stability, and post-translational modification issues.

Comfort using structural biology data to inform and iterate on medicinal chemistry strategies and compound prioritization.

Practical notes

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