Senior Scientist - Protein and Genome Engineer

Genentech•Los Angeles, CA

16d

About The Position

A healthier future. It’s what drives us to innovate. To continuously advance science and ensure everyone has access to the healthcare they need today and for generations to come. Creating a world where we all have more time with the people we love. That’s what makes us Genentech! Genentech San Diego's Department of Genetic Medicine Technology is seeking a highly skilled and motivated Senior Scientist to join our Precision Gene Editing team. This unique opportunity involves spearheading the engineering and optimization of genome editing technologies for diverse biomedical applications. The ideal candidate is an exceptional molecular biologist with demonstrated proficiency in protein engineering with deep expertise in cutting-edge approaches for the development of novel proteins for specific DNA insertion and manipulation of mammalian genomes. The core focus of this role will be the discovery and development of novel enzymes,including transposases, recombinases, and genome editing nucleases (CRISPR-associated proteins, TALEN’s, ZFs) to enhance the efficiency, precision, and safety of DNA manipulation for our proprietary gene insertion platforms. Experience with rational design, structure guided, computational prediction methods, directed evolution and high-throughput screening in diverse biological systems approaches is highly desirable. The successful candidate may be responsible for managing lab Scientist and will thrive in a highly cross-functional, matrixed environment, collaborating closely with multiple teams across the organization to conceive and test new hypothesis and drive the genome engineering enzyme platform forward towards applications within Genentech’s gene and cell therapy programs

Requirements

Ph.D. in Protein Engineering, Structural Biology, Molecular Biology, or a closely related field.
Successful candidates will possess a minimum of two years of productive experience following their Ph.D., whether through postdoctoral training or in an industry setting. A strong record, demonstrated by high-impact publications, patents, and/or successful project transitions, is required.
Demonstrated expertise in protein engineering techniques (e.g., directed evolution, library design, deep mutational scanning). Deep knowledge and demonstrated applications of structural biology and computational prediction tools is required. This encompasses experience with biochemical, molecular, and/or cell biology approaches. Extensive expertise in the engineering and biochemical characterization of DNA-modifying enzymes, such as transposases, recombinases, or CRISPR, TALs, ZFs proteins, is required.
A highly collaborative spirit and excellent written and verbal communication skills are essential, coupled with exceptional creativity and a drive for innovation, and a proven ability to work effectively with multidisciplinary teams.

Nice To Haves

Extensive proficiency in the culture and genetic manipulation of mammalian cell lines and primary cells.
Previous experience engineering chimeric fusions (eg., Prime Editors, based Editors, site-specific transposases) is ideal.
Previous experience with high-throughput protein screening methods and library design and construction is highly desired.
Demonstrated Experience with computational biology approaches, including structure prediction (e.g., AlphaFold) and/or machine learning applied to protein evolution, is preferred.
Hands-on experience with functional molecular assays used for measuring success of genome engineering enzyme activity (e.g. via reporter assays, ddPCR and NGS).
Ability to interpret and manipulate 3D protein structures to guide engineering, utilizing tools like Pymol, ChimeraX, or MOE to visualize protein DNA interfaces is essential.

Responsibilities

Advancing our genome engineering enzyme platform from the bench, driving the rational design and directed evolution of next-generation gene-editing enzymes for optimal activity and specificity.
Develop and implement strategies for rational protein design and directed evolution, utilizing computational tools (e.g., Rosetta, AlphaFold) to predict structure-function relationships.
Establish high-throughput screenings, design and analyse large-scale combinatorial libraries to identify high-activity/high-specificity variants. Integrate bioinformatics pipelines to map genotype-phenotype linkages and utilize machine learning models to predict optimal sequence mutations. Analysis of large sequencing data (Illumina/PacBio).
Utilize structural biology insights (Cryo-EM, X-ray crystallography) to identify and modify key DNA/Protein interaction residues.
Establish and perform cell based assays and protein biochemical assays (protein expression and purification, DNA binding affinity).
Collaborate closely with colleagues and internal experts across different teams in a highly cross-functional setting and ensure that data-driven insights are effectively translated into actionable drug discovery and clinical strategies.
Lead and execute high-quality, hypothesis-driven, and screening-based original research. Drive these projects to early feasibility and proof of concept decision points for potential integration into our in vivo gene and cell therapy pipelines