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.

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.

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 develop ability 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, Alpha Fold / Alpha Fold‑Multimer) and PLM / generative models (ESM, AbMAP, RF diffusion, RF Antibody, ProteinMPNN); generate ML training data and move manual workflows to automation.
• Manage CRO / CDMO partnerships for biologics production, library construction, and characterization.

• 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…