Associate Principal Scientist, Mammalian Cell Line Engineering and Expression Optimization

Associate Principal Scientist

As an Associate Principal Scientist in Oncology Bioscience, you will provide scientific and strategic leadership for mammalian cell line engineering and expression optimization to accelerate discovery of antibody–drug conjugates (ADCs) and bispecific antibodies. A central focus is advancing our in‑house non‑natural amino acid (nnAA) expression system, driving step‑change improvements in productivity, stability, and product quality through host, vector, and process innovations.

You will architect and integrate modern vector designs, site‑specific genomic integration, and process‑aware molecular engineering in CHO and HEK platforms, partnering closely with protein engineering, conjugation chemistry, analytics, and translational teams to deliver differentiated biologics for oncology.

• Scientific leadership and strategy:
  Define and execute the roadmap for cell line engineering and expression optimization for ADCs and bispecifics across CHO and HEK platforms, spanning stable pools and clonal lines, host adaptation, and process‑compatible expression.
• Platform ownership—nnAA expression:
  Own the evolution of our nnAA expression system, driving enhancements in vector architecture, genomic context, secretory pathway tuning, and process parameters to improve titer, consistency, and cell‑line stability; champion adoption across oncology programs.
• Vector and construct design:
  Design and refine expression constructs using advanced elements (e.g., UCOE, MARs/STARs, insulators, enhanced promoters, optimized signal peptides, introns) to strengthen transcriptional robustness, secretion efficiency, and product quality.
• Targeted genomic integration:
  Implement site‑specific integration and scalable stable expression using transposon systems (e.g., Piggy Bac, Sleeping Beauty); evaluate and deploy landing‑pad/CRISPR approaches to reduce clone‑to‑clone variability and enhance long‑term stability.
• Expression optimization:
  Lead transient and stable optimization using media/feed screening, temperature and pH shifts, chemical chaperones/additives, and DoE‑driven experiments to improve titer, viability, and critical quality attributes (CQAs).
• Clonal selection strategies:
  Establish and harmonize clonal selection workflows (limiting dilution, FACS, imaging‑based screening) aligned with CQAs for bispecifics and ADC‑ready antibodies.
• Analytics partnership and workflows:
  Set robust protein quantitation and purification workflows (ELISA/Octet, HPLC/UPLC; affinity, IEX, SEC) and partner with analytics to profile aggregation, glycosylation, charge variants, and stability, feeding insights back into design.
• Cross‑functional influence:
  Collaborate with antibody engineering on bispecific format selection (e.g., knob‑in‑hole) and with chemistry on ADC conjugation readiness (site‑specific tags, engineered cysteines, glycan‑based strategies) to ensure expression suitability and DAR control.
• Automation and scale‑out:
  Deploy and scale automation and high‑throughput screening (liquid handlers, plate readers, mini‑bioreactors) to accelerate construct/condition evaluation and enable data‑driven decisions.
• Data integrity and decision packages:
  Maintain meticulous records, ensure data integrity, and deliver concise decision packages on expression performance, stability, and CQAs to guide portfolio progression.
• People leadership and mentoring:
  Provide day‑to‑day technical mentorship for junior scientists and contribute to capability‑building, best‑practice dissemination, and continuous improvement of platform and nnAA workflows.

• PhD with 3+ years, or Master’s with 6+ years, or Bachelor’s with 8+ years of substantial, relevant industry experience in Cell Biology, Molecular Biology, Biochemistry, Bioengineering, or a related field.
• Proven expertise in mammalian cell line engineering and protein expression, with hands‑on experience in CHO and/or HEK systems.
• Track record of leading projects and mentoring scientists to milestones in a multidisciplinary R&D environment.
• Demonstrated ability to collaborate cross‑functionally with protein engineering, chemistry, analytics, and process…