Principal Scientist, TCR Optimization

BioSpace; Cambridge (MA); Hybrid; USD 143,000 - 257,000; Full time

Benefits offered by this job

Healthcare benefits

Well-being programs

Paid time off

Job summary

Moderna is seeking a Principal Scientist to lead TCR optimization workflows for next-generation therapeutics. You will build scalable experimental platforms to improve affinity, developability, expression, and functional potency, working closely with discovery, computational biology, AI/ML, and preclinical teams.

You will lead end-to-end optimization campaigns, design libraries informed by biology, and interpret complex datasets to advance optimized TCR candidates for TCR-T and related

Qualifications

• PhD with 5+ years in TCR engineering, protein engineering, or related therapeutic discovery field.
• Experience executing TCR optimization workflows linking binding, developability, and potency.
• Hands-on with display technologies, library design, and affinity maturation.
• Ability to lead complex workflows and deliver datasets on timelines.

Responsibilities

• Build and optimize scalable TCR optimization workflows using display technologies and directed evolution.
• Establish end-to-end pipelines from design to lead selection and validation.
• Design rational/semi-rational TCR libraries informed by biology and developability.
• Lead multi-parameter optimization campaigns balancing affinity, stability, and potency.
• Collaborate with computational scientists to integrate data into decisions.
• Interpret complex screening and biophysical datasets to prioritize candidates.
• Deliver optimized binders for therapeutic evaluation including TCR-T and TCR engager platforms.
• Adopt new display/screening/automation technologies to improve throughput.
• Communicate results, risks, and recommendations to cross-functional teams.

Skills

TCR engineering

Protein engineering

Directed evolution

Display technologies

Cross-functional collaboration

Data interpretation

AI/ML collaboration

Education

PhD in immunology or related

Tools

NGS platforms

Biophysical characterization

Molecular biology

Sequence analysis

Job description

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 screening, 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.

About Moderna

Since 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 Opportunities

Moderna 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.

Accommodations

We’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 [e-mail].

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.