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

Eli Lilly and Company • San Diego, CA

4d • 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. The role focuses on molecular biology and recombinant expression of diverse protein targets, including challenging 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.

The position is based full-time on site in a laboratory/bench setting in San Diego, California. The anticipated wage is $72,000–$189,200. Full-time employees are also eligible for a company bonus, depending in part on company and individual performance, and a comprehensive benefits program for eligible employees.

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 such as Gibson, Golden Gate, In-Fusion, and site-directed mutagenesis, and ability to design constructs for structurally and biochemically diverse targets.
• Hands-on proficiency across E. coli and baculovirus/insect host systems, with experience selecting an appropriate host for a target.
• Strong organizational skills and attention to detail.
• Effective written and verbal communication skills.
• Proficiency with standard laboratory and office software.

Nice To Haves

• Experience with yeast expression and large-scale mammalian expression, such as CHO or HEK293.
• Experience with membrane protein expression, such as GPCRs, transporters, or ion channels; required at the Senior Principal Scientist level.
• 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; this is highly valued and may indicate suitability for the more senior level.
• 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 target-specific constructs using 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 expression of recombinant proteins in E. coli and insect cells using shake flasks, Wave/rocker bag systems, and stirred-tank bioreactors to provide material for purification and project needs.
• 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 in writing and verbally to project stakeholders and team leadership.
• Mentor and provide technical guidance to less experienced colleagues, as appropriate to the level of the role.

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, including 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.
• Employee resource groups (ERGs), which offer support networks and are open to all employees.

What This Job Offers

• Job Type: Full-time
• Career Level: Senior