Principal Scientist, TCR Optimization

The RoleThe 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 DoBuild, 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 & BenefitsAt 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 needsA holistic approach to well-being, with access to fitness, mindfulness, and mental health supportFamily planning benefits, including fertility, adoption, and surrogacy supportGenerous paid time off, including vacation, volunteer days, sabbatical, global recharge days, and a discretionary year-end shutdownSavings and investments to help you plan for the futureLocation-specific perks and extrasThe 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.About ModernaSince our founding in 2010, we have aspired to build the leading mRNA technology platform, the infrastructure to reimagine how medicines are created and delivered, and a world-class team. 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 every day, our people are the driving force behind our scientific progress and our culture. Together, we are creating a culture of belonging and building an organization that cares deeply for our patients, our employees, the environment, and our communities. We are proud to have been recognized as a Science Magazine Top Biopharma Employer, a Fast Company Best Workplace for Innovators, and a Great Place to Work in the U.S. If you want to make a difference and join a team that is changing the future of medicine, we invite you to visit modernatx.com/careers to learn more about our current opportunities. 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. Equal OpportunitiesModerna is committed to equal employment opportunity and non-discrimination for all employees and qualified applicants without regard to a person's race, color, sex, gender identity or expression, age, religion, national origin, ancestry or citizenship, ethnicity, disability, military or protected veteran status, genetic information, sexual orientation, marital or familial status, or any other personal characteristic protected under applicable law. Moderna is a place where everyone can grow. If you meet the Basic Qualifications for the role and you would be excited to contribute to our mission every day, please apply!Moderna is an E-Verify Employer in the United States. We consider qualified applicants regardless of criminal histories, consistent with legal requirements. AccommodationsWe’re focused on attracting, retaining, developing, and advancing our employees. By cultivating a workplace that values diverse experiences, backgrounds, and ideas, we create an environment where every employee can contribute their best. Moderna is committed to offering reasonable accommodations to qualified job applicants with disabilities. Any applicant requiring an accommodation in connection with the hiring process and/or to perform the essential functions of the position for which the applicant has applied should contact the Accommodations team at View email address on click.appcast.io. Export Control Notice This position may involve access to technology or data that is subject to U.S. export control laws, including the Export Administration Regulations (EAR). As such, employment is contingent upon the applicant’s ability to access export-controlled information in accordance with U.S. law. Due to the nature of the work and regulatory requirements, only individuals who qualify as U.S. persons (citizens, permanent residents, asylees, or refugees) are eligible for this position. For this role Moderna is unable to sponsor non-U.S. persons to apply for an export control license. #LI-NH1-SummaryLocation: Cambridge, Massachusetts; ResearchType: Full time