Principal Scientist, TCR Optimization
$142,500–$256,500 year
On-siteCambridge, Massachusetts, United States or Research, Victoria, Australia
Job Summary
Build and execute scalable TCR optimization workflows using display technologies and directed evolution to improve affinity, specificity, stability, and therapeutic-format compatibility. Establish an end-to-end pipeline connecting library design, screening, candidate recovery, and functional validation to deliver optimized binders for TCR-T and TCR engager modalities. Lead multi-parameter campaigns that balance potency, developability, and safety risks while partnering with computational, AI/ML, and preclinical teams to integrate structural modeling and NGS data into iterative decisions. Interpret complex binding and biophysical datasets to prioritize candidates and recommend optimization strategies. Evaluate new automation and protein engineering technologies to enhance throughput and candidate quality.
Required Qualifications
- PhD in immunology, protein engineering, molecular biology, biochemistry, biophysics, cell biology, or related disciplines
- At least 5 years of post-PhD experience in TCR engineering, protein engineering, directed evolution, display-based screening, or a closely related therapeutic discovery discipline
- Demonstrated experience executing TCR or TCR-mimetic optimization workflows that connect binding, stability, expression, developability, and functional potency data
- Hands-on experience with display technologies, rational or semi-rational library design, affinity maturation, specificity engineering, and developability optimization
- Experience designing and interpreting binding, stability, expression, functional potency, or biophysical characterization assays
- Demonstrated ability to lead complex experimental workflows, troubleshoot technical challenges, and deliver high-quality datasets under active program timelines
- Experience collaborating with computational biology, AI/ML, NGS, reagent generation, functional assay, preclinical, or external partner teams
- Ability to independently make and communicate key decisions based on experimental data and stakeholder feedback
- Excellent written, presentation, and interpersonal communication skills, including the ability to communicate scientific results, risks, tradeoffs, and recommendations to cross-functional teams
- 70% in-office structure
- Smoke-free, alcohol-free, and drug-free work environment
- U.S. person status (citizens, permanent residents, asylees, or refugees)
- Ability to access export-controlled information in accordance with U.S. law
Desired Qualifications
- Strong understanding of TCR-pMHC recognition, T cell biology, therapeutic TCR formats, and the tradeoffs among affinity, specificity, stability, expression, developability, and potency
- Experience in TCR cross-reactivity assessment and off-target risk considerations
- Experience integrating computational predictions and wet-lab screening data into practical engineering decisions
- Experience using sequence analysis, NGS datasets, structure-guided design, or sequence-function modeling to inform protein optimization
- Experience evaluating or implementing new display, screening, automation, or protein engineering technologies
- Demonstrated ability to operate as both a hands-on scientific contributor and a cross-functional project leader in a fast-paced, program-driven environment
- A desire to make an impact as part of a high-growth, transformational company that is Bold, Relentless, Curious, and Collaborative
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