Senior - Principal Scientist - Antibody Optimization and Engineering

Prellis Biologics, Inc; Berkeley (CA); Hybrid; USD 141,000 - 216,000; Full time

Benefits offered by this job

Medical coverage

401(k) plan

Flexible work model

Job summary

Prellis Biologics, Inc. seeks a Senior / Principal Scientist in Antibody Optimization and Engineering to lead high-throughput discovery initiatives. You will own display platforms, drive affinity maturation, and integrate computational design with ML/data science to accelerate lead candidates toward development.

The role involves CRO/CDMO partnerships, cross-functional collaboration with NGS, Bioinformatics, and Protein Sciences, and hands-on lab leadership in a fast-paced environment.

Qualifications

• Ph.D. in Biochemistry, Bioengineering, Molecular Biology, Protein Engineering, or related field (Senior Scientist: 3–5 yrs; Principal Scientist: 5+ yrs).
• Proven track record optimizing antibody leads: affinity maturation and liability engineering.

Responsibilities

• Lead optimization and engineering with emphasis on affinity maturation and liability engineering.
• Build and lead yeast/phage display platforms for antibody formats (scFv, Fab, IgG, VHH).
• Drive computational design using structure-based tools and ML to move DBTL loop forward.

Skills

Antibody optimization

Yeast display

Phage display

Affinity maturation

Computational design

Python / ML

Leadership

Education

PhD in Biochemistry or related

Tools

PyMOL

Schrödinger

AlphaFold/AlphaFold-Multimer

NGS / library prep

Job description

Senior - Principal Scientist - Antibody Optimization and Engineering

Full Time

The heart of Prellis Bio’s strategy is the combination of novel, cutting‑edge methods in machine learning, biology at scale, and next‑gen antibody discovery that address long‑standing industry‑wide problems in the drug development pipeline. Prellis Biologics uses proprietary technology to 3D print human lymph node organoids, enabling the rapid & diverse discovery of human antibody therapeutic candidates for a range of applications. To drive this forward, we are assembling an incredible team of discovery biologists, computational scientists, and protein scientists who want to make a difference to this important problem.

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.

Qualifications

• Ph.D. in Biochemistry, Bioengineering, Molecular Biology, Protein Engineering, or related field: Senior Scientist (PhD + 3‑5 yrs); Principal Scientist (PhD + 5+ yrs).
• Proven track record optimizing antibody leads: affinity maturation and liability engineering (sequence / chemical liability removal, aggregation and immunogenicity mitigation, humanization).
• Hands‑on with yeast and / or phage display across multiple formats (scFv, Fab, IgG, VHH); TITE‑Seq, DMS, or comparable sequence‑function methods.
• Strong molecular cloning, mutagenesis, and library construction (Gibson, SSM, EP‑PCR, oligo‑pool); NGS library prep and enrichment analysis.
• Hands‑on with high‑throughput flow platforms (iQue, MACSQuant, or comparable) and FACS‑based screening cascades.
• Computational fluency: PyMOL, Schrödinger (BioLuminate / Maestro), AlphaFold / AlphaFold‑Multimer, MD, or equivalent; Python (PyTorch, pandas, NumPy), R, and HPC.
• Experience applying protein language models and / or generative models (ESM, AbMAP, RFdiffusion, RFAntibody, ProteinMPNN, or equivalent); transfer learning / fine‑tuning on experimental data.
• Experience managing CRO / CDMO partnerships for biologics production and characterization.
• Leadership experience, including mentoring junior scientists; strong scientific communication; publications, presentations, or patents; thrives in cross‑functional collaboration.

Bonus Experience

• Biologics reformatting, multispecific assembly, and Fc engineering.
• Continuous directed evolution (OrthoRep, PACE) or alternative display platforms.
• Liquid‑handling automation and LIMS / ELN.
• Antibody expression and QC support (production, analytics, biophysical characterization).

About Prellis Biologics

At Prellis we integrate human biology with machine learning. We aim to revolutionize drug discovery by harnessing the power of the human immune system with tightly integrated machine learning to develop next‑generation antibody therapeutics with unparalleled speed, precision, and safety. We are committed to empowering our pharmaceutical partners with access to the most promising fully human antibody candidates rapidly identified from the human immune repertoire, enabling them to bring life‑changing treatments to patients faster than ever before. Prellis Biologics is a pre‑IPO biotech located in Berkeley, CA with a team‑oriented, inclusive, and family‑friendly culture. Our growing pipeline targets high unmet

patient needs across therapeutic areas including metabolic disease, inflammation, and oncology. Prellis has raised funding from top investors, including Celesta, Khosla Ventures, SOSV, and Avidity Partners.

What You Can Expect Of Us

As we work to develop treatments that take care of others, we also work to care for your professional and personal growth and well‑being. From our competitive benefits to our collaborative culture, we’ll support your journey every step of the way.

Actual salary will vary based on several factors including, but not limited to, relevant skills, experience, and qualifications.

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

Prellis does not have an application deadline for this position; we will continue accepting applications until we receive a sufficient number or select a candidate for the position.

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.

$141,000 - $216,000