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Principal Scientist, Genome Engineering

Cambridge, Massachusetts, United States

About Stylus Medicine:

Stylus Medicine is developing transformative in vivo genetic medicines to unlock cures. Stylus combines engineered recombinases with non-viral delivery to specifically encode therapeutics. The company’s approach is versatile and modular, with potential therapeutic application across oncology, autoimmune, genetic diseases, and beyond.

About the Role:

Stylus Medicine is seeking a collaborative and creative Principal Scientist, Genome Engineering to join our Genome Sciences & Engineering team. This key role will drive discovery and engineering efforts - leading multiple high-throughput screening campaigns, advancing discovery and engineering approaches, and collaborating across diverse R&D teams. Reporting to the Director, Genome Engineering, this role is ideal for an individual who thrives in a fast-paced environment and enjoys tackling complex problems to expand the frontiers of genome editing with recombinases.

Key Responsibilities & Accountabilities:

  • Lead genome engineering initiatives to enhance enzyme activity and performance in support of Stylus' therapeutic pipeline
  • Design and execute high-throughput arrayed and pooled screening campaigns for de novo discovery, engineering, and mechanistic characterization of recombinases
  • Develop rigorous frameworks for evaluating and prioritizing engineered variants, guiding candidate selection through validation and into preclinical development
  • Integrate diverse molecular readouts - including dPCR, RT-qPCR, flow cytometry, and NGS to drive data-informed decision-making across programs
  • Build and scale screening capabilities by mentoring scientists and establishing best practices in mutagenesis, variant characterization, and high-throughput workflows
  • Identify and implement emerging technologies that strengthen Stylus' recombinase platform and expand its therapeutic reach

Qualifications & Skills:

  • PhD in Molecular Biology, Biochemistry, Synthetic Biology, Chemical Biology, or a related discipline, with 6+ years of relevant experience in high-throughput screening and protein engineering
  • Demonstrated hands-on experience developing or optimizing genome editing tools (e.g., CRISPR nucleases, recombinases, polymerases, or transcriptional effectors)
  • Proven ability to design and execute arrayed and pooled high-throughput screening workflows across diverse cell types, including primary cells (T cells, hepatocytes) and standard cancer cell lines
  • Familiarity with pooled screening library generation and next-generation sequencing platforms (Illumina, Nanopore, or PacBio)
  • Familiarity with structural modelling tools like AlphaFold, RoseTTAFold, Boltz-2 etc. is a plus
  • Experience mentoring scientists and managing complex engineering projects is strongly preferred
  • Exceptional organizational skills and ability to manage complex datasets and overlapping projects as well as strategically plan projects to maximize scientific impact
  • Excellent communication skills, with the ability to translate concepts for diverse audiences
  • Collaborative mindset with a team-first attitude

Pay Range: $172,500 - $187,500

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