Senior - Principal Scientist - Antibody Optimization and Engineering Berkeley, CA

Position Summary: We are seeking a Senior / Principal Scientist — Antibody Optimization and Engineering to join our High Throughput Discovery group. You will be responsible for: Establishing Prellis's yeast / phage display platform as the backbone of our antibody optimization engine, owning the scientific strategy, and standing up end-to-end workflows. Leading and executing display-based optimization and engineering campaigns, including library design, affinity maturation, and property improvement. Applying computational engineering to design and engineer antibodies using structural, generative, and sequence-function models; partnering with Data Science / AI/ML to generate training data and close the design-build-test-learn (DBTL) loop. This role sits within a highly cross-functional High Throughput Discovery group, working closely with NGS / Bioinformatics, Protein Sciences, and Data Science / AI/ML. The ideal candidate will thrive in a dynamic, hands-on environment and play a critical role in delivering life-changing therapeutics.

Responsibilities: Lead antibody optimization and engineering with a strong emphasis on affinity maturation and liability engineering to refine and advance lead candidates toward development. Core activities: Build out the yeast/phage display platforms across scFv, Fab, IgG, and VHH formats: strains, vectors, induction and labeling protocols, FACS sorting, and QC.Lead biopanning campaigns for affinity maturation and property improvement; design focused and diversified libraries (alanine scanning, site-saturation, CDR-focused, oligo-pool); apply DMS, TITE-Seq, and NGS-based enrichment to drive sequence-function understanding. Partner with the computational liability team on developability polishing: design experimental approaches and focused libraries to remove sequence / chemical liabilities, mitigate aggregation and immunogenicity, and humanize when needed. Drive computational design with Data Science / AI/ML: apply structural tools (PyMOL, Schrödinger, AlphaFold / AlphaFold-Multimer) and PLM / generative models (ESM, AbMAP, RFdiffusion, RFAntibody, ProteinMPNN); generate ML training data and move manual workflows to automation. Manage CRO / CDMO partnerships for biologics production, library construction, and characterization.

Benefits: In addition to the base salary, Prellis offers compelling benefits based on eligibility, comprising health and welfare plans for staff and eligible dependents, financial plans with opportunities to save toward retirement or other goals, work/life balance, and career development opportunities that may include:

• A competitive employee benefits package, including group medical, dental, and vision coverage, life and disability insurance, flexible spending accounts, and a 401(k) plan
• Stock-based long-term incentives
• Holiday package including a 1+ week winter shutdown
• Flexible work models, including remote and hybrid working arrangements, where possible
• Application Deadline

Equal Opportunity: Prellis Bio is an equal opportunity employer. All applicants will be considered for employment without attention to race, color, religion, sex, sexual orientation, gender identity, national origin, veteran, or disability status. We believe diversity, equity, and inclusion need to be at the foundation of our culture. We work hard to bring together diverse teams, grounded in a wide range of expertise and life experiences, and work even harder to ensure those teams thrive in inclusive, growth-oriented environments supported by equitable company and team practices. All candidates can expect equitable treatment, respect, and fairness throughout the interview process.