Lead TCR Optimization Scientist

Initial Therapeutics, Inc.; Cambridge (MA); On-site; USD 143,000 - 257,000; Full time

Benefits offered by this job

Healthcare benefits

Fitness and mindfulness programs

Family planning benefits

Generous paid time off

Savings and investments

Location-specific perks

Job summary

Moderna seeks a Principal Scientist to lead TCR optimization workflows for next-generation TCR-based therapeutics. The role emphasizes scalable experimental platforms to improve affinity, specificity, stability, and developability across multiple therapeutic formats.

You will direct end-to-end optimization campaigns, partner with computational teams, and deliver high-quality data to advance candidates through iterative wet-lab and computational design.

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.

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 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.

Skills

TCR engineering

Directed evolution

Protein engineering

Data interpretation

Cross-functional collaboration

Education

PhD in immunology, protein engineering, molecular biology, biochemistry, biophysics, cell biology, or related disciplines

Tools

Display technologies

Sequence analysis

NGS

Biophysical characterization

Job description

Moderna seeks a Principal Scientist to lead TCR optimization workflows for next-generation TCR-based therapeutics. The role emphasizes scalable experimental platforms to improve affinity, specificity, stability, and developability across multiple therapeutic formats.

You will direct end-to-end optimization campaigns, partner with computational teams, and deliver high-quality data to advance candidates through iterative wet-lab and computational design.