Principal Scientist, Genome Engineering

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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