Principal Scientist, TCR Optimization

Moderna’s Therapeutics Research group is seeking a Principal Scientist to build, optimize, and execute T cell receptor (TCR) optimization workflows for next-generation TCR-based therapeutics. This role will lead the development of scalable experimental platforms to improve key TCR properties, including affinity, cross-reactivity, stability, expression, developability, functional potency, and compatibility with mRNA-expressed therapeutic formats.

Responsibilities

• Build, optimize, and execute scalable TCR optimization workflows using display technologies and directed evolution approaches to improve affinity, specificity, stability, expression, developability, and therapeutic-format compatibility.
• Establish an end-to-end TCR optimization pipeline connecting library design, display-based screening, candidate recovery, sequence analysis, molecular characterization, functional validation, and lead selection.
• Design rational and semi-rational TCR libraries informed by sequence, structure, pHLA biology, cross-reactivity risk, developability considerations, and therapeutic-format requirements.
• Lead multi-parameter and iterative optimization campaigns balancing affinity, specificity, stability, expression, developability, functional potency, and safety-related risk.
• Partner with computational scientists to incorporate TCR cross-reactivity, structural modeling, sequence-function relationships, and developability data into iterative optimization decisions.
• Interpret complex screening, binding, biophysical, and functional datasets to prioritize candidates and recommend optimization strategies.
• Support current and future TCR therapeutic programs by delivering optimized binders suitable for therapeutic evaluation, including TCR-T, TCR engager, and other TCR-based modalities.
• Evaluate and implement new display, screening, automation, and protein engineering technologies to improve throughput, specificity, scalability, or candidate quality.
• Collaborate with AI/ML, NGS, functional assay, reagent generation, preclinical, and external partner teams to ensure optimization workflows generate high-quality, decision-ready data.
• Communicate scientific strategy, experimental results, technical risks, tradeoffs, and recommendations to multidisciplinary project and platform teams.

Requirements

• 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 connecting 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.
• 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.

Preferred Qualifications

• Strong understanding of TCR-pMHC recognition, T cell biology, therapeutic TCR formats, and 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.
• Desire to make an impact as part of a high-growth, transformational company.

Benefits

• Competitive healthcare, plus voluntary benefit programs to support unique needs.
• Holistic well-being support, including fitness, mindfulness, and mental health resources.
• Family planning benefits, including fertility, adoption, and surrogacy support.
• Generous paid time off, including vacation, volunteer days, sabbatical, global recharge days, and a discretionary year-end shutdown.
• Savings and investments to help plan for the future.
• Location-specific perks and extras.

Pay

The salary range for this role is $142,500.00 - $256,500.00. An individual’s position within the salary range will be based on competencies, relevant education, qualifications, certifications, experience, skills, performance, and business or organizational needs. The successful candidate may be eligible for an annual discretionary bonus, other incentive compensation, or equity award, subject to company plan eligibility criteria and individual performance.

Schedule

Moderna embraces a 70/30 work model, with 70% in-office collaboration to foster innovation, teamwork, and direct mentorship.

About the Company

Since our founding in 2010, Moderna has aspired to build the leading mRNA technology platform, reimagining how medicines are created and delivered. We believe in giving our people a platform to change medicine and an opportunity to change the world. By living our mission, values, and mindsets daily, our team drives scientific progress and fosters a culture of belonging.