The Role

The Therapeutics Research group at Moderna is seeking a talented, experienced, and highly motivated Principal Scientist to build, optimize, and execute T cell receptor optimization workflows for next-generation TCR-based therapeutics.

This individual 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. The successful candidate will apply deep expertise in display-based protein engineering, TCR biology, biophysical characterization, cross-reactivity screning, and functional assays to advance TCR candidates through iterative wet-lab and computational optimization.

This candidate will work closely with cross-functional partners in TCR discovery, protein engineering, computational biology, AI/ML, functional assay development, translational science, and preclinical development. The role is well suited for a hands-on scientist who can execute complex experimental workflows, interpret multi-parameter datasets, and contribute to the generation of optimized TCR candidates with the potency, specificity, and developability required for therapeutic advancement.

Here's What You'll Do

• 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 that connects 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 that balance 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 that can 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.

Here's What You'll Need (Basic 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.

Here's What You'll Bring to the Table (Preferred 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.

Pay & Benefits

At Moderna, we believe that when you feel your best, you can do your best work. That's why our benefits and well-being resources are designed to support you-at work, at home, and everywhere in between.

• Competitive healthcare, plus voluntary benefit programs to support your unique needs
• A holistic approach to well-being, with access to fitness, mindfulness, and mental health support
• 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 you plan for the future
• Location-specific perks and extras

The salary range for this role is $142,500.00 - $256,500.00. This is the lowest to highest salary we in good faith believe we would pay for this role at the time of this posting. An individual's position within the salary range will be based on several factors including, but not limited to, specific 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.

Our Working Model

As we build our company, we have always believed an in-person culture is critical to our success. Moderna champions the significant benefits of in-office collaboration by embracing a 70/30 work model. This 70% in-office structure helps to foster a culture rich in innovation, teamwork, and direct mentorship. Join us in shaping a world where every interaction is an opportunity to learn, contribute, and make a meaningful impact.

Moderna is a smoke-free, alcohol-free, and drug-free work environment.