Senior Research Scientist I- CRISPR Screening

The Broad Institute’s Genomics Platform seeks a highly motivated and specialized Senior Research Scientist to lead our high-throughput CRISPR screening efforts. This role is designed for a scientist with deep expertise in functional genomics, specializing in the design, execution, and analysis of pooled CRISPR screens across diverse cellular models, with a primary focus on induced pluripotent stem cells (iPSCs).

In this role, you will bridge the gap between complex genetic engineering and large-scale screening. You will be responsible for the entire screening lifecycle: from custom library design and transduction to the differentiation of iPSCs into specialized lineages (e.g., neurons, cardiomyocytes and other lineages) and the final readout via scRNA-seq, NGS, or imaging (OPS). This is a high-impact role requiring a blend of innovative experimental design, meticulous laboratory management, and collaborative leadership.
Characteristic Duties

· Screen Design & Execution: Serve as the primary architect for pooled CRISPR (knockout, activation, interference, base editing) screens. This includes target gene composition and gRNA library design for different readouts, oversight of library cloning and virus production, and determining optimal transduction parameters in complex cell types (e.g. iPSCs, primary cells, and others).

· iPSC Screening Platform Management: Lead the maintenance, expansion, and 3D culture, and high-efficiency differentiation of iPSC lines into biologically relevant models (e.g., neurons, cardiomyocytes, immune cells) specifically for screening applications (CRISPR screening, drug screening).

· Technical Leadership: Direct the development of screening protocols, including the optimization of "cell-to-data" workflows that integrate with automated liquid handling and high-throughput sequencing.

· Stakeholder Collaboration: Partner with internal and external investigators to translate biological questions into robust screening assays, providing expert guidance on library selection and phenotypic readouts.

· Data Oversight: Work closely with computational biologists to interpret screening results, ensuring high-quality data generation and validating "hits" through secondary assays and arrayed validation.

· Team Mentorship: Lead and mentor a dedicated team of Research Associates, fostering a culture of scientific rigor, innovation, and career development.

· Platform infrastructure and scaling: Oversee laboratory logistics for the screening pipeline, including reagent scaling (large-scale DNA and virus prep), equipment maintenance, and safety compliance.

Experience and Requirements

· Education: PhD in Molecular Biology, Genetics, Bioengineering, or a related field with 5+ years of postdoctoral or industry experience; OR a Master’s degree with 8+ years of specialized experience.

· Core Expertise: Proven track record in pooled CRISPR screening is mandatory. This includes hands-on experience with library cloning, lentiviral production, and screen execution.

· Cellular Expertise: Deep familiarity with iPSC culture and differentiation protocols. Experience with long-term cultures required for differentiation in 2D and 3D is highly preferred.

· Molecular Skills: Expert proficiency in molecular cloning (Gibson assembly, Golden Gate, etc.), NGS library preparation, and qPCR/ddPCR for library quantification.

· Analytical Mindset: Comfortable with basic bioinformatics tools for gRNA design and initial screening data QC; ability to work fluidly with data scientists for complex hits analysis.

· Automation (Optional/Preferred): Familiarity with liquid handling platforms (e.g., Hamilton, Beckman, Agilent) and their integration into high-throughput screening workflows is a significant plus.

· Adaptability: Ability to thrive in a fast-paced environment, managing multiple screening projects simultaneously without compromising quality.

· Communication: Exceptional ability to present complex functional genomics data to stakeholders and contribute to high-impact scientific publications.