Principal Scientist, Genome Engineering

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