Principal / Sr. Principal Scientist - Molecular Biology & Protein Expression

Lilly•San Diego, CA
•$110,250 - $189,200•Onsite

About The Position

The Principal Scientist / Senior Principal Scientist in Molecular Biology & Protein Expression will join a centralized molecular biology and protein expression platform team within Lilly Small Molecule Discovery (LSMD). The role focuses on molecular biology and recombinant expression of diverse protein targets, including challenging targets such as membrane proteins, across multiple host systems. The scientist will own complex expression challenges, mentor less experienced colleagues, and drive platform development, including automation and higher-throughput workflows. This is a full-time, on-site laboratory/bench role in San Diego, California. The position requires the ability to lift up to 25 pounds, with or without reasonable accommodation. The anticipated wage is $110,250–$189,200. Full-time employees are eligible for a company bonus, depending in part on company and individual performance, and a comprehensive benefits program, subject to eligibility.

Requirements

  • B.S. or M.S. in Biological Sciences, Biochemistry, Molecular Biology, Chemistry, Biophysics, or a related discipline, with typically 5 or more years of relevant hands-on molecular cloning and recombinant protein expression experience, or equivalent demonstrated impact.
  • Proficiency with molecular cloning techniques, including Gibson, Golden Gate, In-Fusion, and site-directed mutagenesis, and ability to design constructs for structurally and biochemically diverse targets.
  • Hands-on proficiency across the stated host systems and experience selecting an appropriate host for a given target.
  • Strong organizational skills and attention to detail.
  • Effective written and verbal communication skills.
  • Proficiency with standard laboratory and office software.
  • At the Senior Principal Scientist level, experience with membrane protein expression, such as GPCRs, transporters, or ion channels.
  • Ability to meet the physical requirements of the position, including lifting up to 25 pounds, with or without reasonable accommodation.

Nice To Haves

  • Experience with yeast expression and large-scale mammalian expression, such as CHO or HEK293.
  • Experience with bioreactor process development, including dissolved oxygen, pH, and feeding strategy, and Wave/rocker bag scale-up workflows.
  • Experience with large-scale (≥10 L) purification workflows, including AKTA FPLC.
  • Experience with laboratory automation and high-throughput cloning or expression workflows, such as liquid handling and colony picking.
  • Familiarity with cell-free protein synthesis systems or other specialized expression strategies.
  • Demonstrated experience mentoring and providing technical guidance to junior scientists.
  • Experience with electronic laboratory notebooks, such as Benchling, LIMS, or protein sample tracking databases.

Responsibilities

  • Independently design and execute molecular cloning strategies, including Gibson assembly, Golden Gate, In-Fusion, restriction/ligation cloning, SLIC, and site-directed mutagenesis; design constructs with appropriate tags, truncations, fusion partners, and codon optimization.
  • Perform small-scale recombinant protein expression across E. coli, baculovirus/insect cells, and mammalian cells, using transient transfection, baculovirus infection, and adherent or suspension cell culture workflows to screen constructs, hosts, and expression conditions.
  • Execute large-scale recombinant protein expression in E. coli and insect cells using shake flasks, Wave/rocker bag systems, and stirred-tank bioreactors.
  • Assess expression and small-scale material using SDS-PAGE, Western blot, capillary electrophoresis, analytical SEC, and UV spectroscopy to support construct triage and expression optimization.
  • Develop and improve platform workflows through parallelization, standardization, and automation of cloning and expression screening to increase throughput and reproducibility.
  • Collaborate with purification, structural biology, and project teams to align construct design and expression strategies with downstream needs.
  • Maintain accurate and timely experimental records in a Laboratory Information Management System (LIMS) and electronic laboratory notebooks, upholding scientific rigor and data integrity.
  • Communicate experimental progress, key results, risks, program status, and proposed next steps clearly to project stakeholders and team leadership.
  • Mentor less experienced colleagues and provide technical guidance.

Benefits

  • Company bonus, depending in part on company and individual performance.
  • Eligibility to participate in a company-sponsored 401(k).
  • Pension.
  • Vacation benefits.
  • Eligibility for medical, dental, vision, and prescription drug benefits.
  • Flexible benefits, such as healthcare and/or dependent day care flexible spending accounts.
  • Life insurance and death benefits.
  • Certain time off and leave of absence benefits.
  • Well-being benefits, including an employee assistance program, fitness benefits, and employee clubs and activities.
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