Associate Principal Scientist, Mammalian Cell Line Engineering and Expression Optimization for ADCs and Bispecifics, with Focus on Non Natural Amino Acid Expression Systems

AstraZeneca • Gaithersburg, MD

4d • $142,378 - $213,566

About The Position

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.

Requirements

• 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 development.

Nice To Haves

• Depth in molecular cloning and expression optimization: vector architecture, promoter/enhancer selection, codon and signal peptide optimization, intron/UCOE utilization.
• Experience building stable expression systems, including transposons, UCOE elements, and evaluation of CRISPR‑based landing pads; familiarity with engineering relevant to nnAA expression (e.g., orthogonal promoters, engineered tRNAs/aaRS, noncanonical secretion tags/trafficking signals).
• Proven track record in antibody expression and purification; familiarity with bispecific formats and ADC design principles (linker/payload strategies, site‑specific conjugation readiness).
• Strong background in protein quantitation and purification (ELISA/Octet, spectrophotometry, HPLC/UPLC; affinity, IEX, SEC) with attention to aggregation, glycosylation, charge heterogeneity, and stability.
• Demonstrated experience optimizing and troubleshooting using DoE and statistical approaches; ability to interpret data from mini‑bioreactors and fed‑batch systems, including scalability assessments for novel expression modalities.
• Familiarity with automation and high‑throughput screening; experience with FACS‑based clone selection or imaging‑enabled screening is a plus.
• Willingness to engage with conjugation methods and chemistry to ensure expression products are suitable for ADC payload attachment and downstream characterization.
• Excellent organizational skills, rigorous record keeping, and compelling data presentation tailored to portfolio decision‑making.
• Ability to multitask and manage shifting priorities in a fast‑paced oncology research environment.

Responsibilities

• 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., PiggyBac, 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.

Benefits

• Our positions offer eligibility for various incentives—an opportunity to receive short-term incentive bonuses, equity-based awards for salaried roles and commissions for sales roles.
• Benefits offered include qualified retirement programs, paid time off (i.e., vacation, holiday, and leaves), as well as health, dental, and vision coverage in accordance with the terms of the applicable plans

What This Job Offers

• Job Type: Full-time
• Career Level: Mid Level
• Education Level: Ph.D. or professional degree