Principal Scientist, TCR Optimization at ModernaTX, Inc. in Cambridge, Massachusetts

Principal Scientist, Therapeutics Research

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, develop ability, 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 develop ability 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, develop ability, 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, develop ability considerations, and therapeutic-format requirements.
• Lead multi-parameter and iterative optimization campaigns that balance affinity, specificity, stability, expression, develop ability, functional potency, and safety-related risk.
• Partner with computational scientists to incorporate TCR cross-reactivity, structural modeling, sequence-function relationships, and develop ability 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, develop ability, and functional potency data.
• Hands-on experience with display technologies, rational or semi-rational library design, affinity maturation, specificity engineering, and develop ability 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, develop ability, and potency.
• Experience in TCR cross-reactivity assessment and off-target risk considerations.
• Experience integrating computational predictions and wet-lab screening data into practical…