AI-Enabled iPSC Disease Modeling & Functional Genomics

Job Title and Location AI-Enabled iPSC Disease Modeling & Functional Genomics – Cambridge, MA Job Overview Sanofi is building a next‑generation neuroscience research engine focused on defining the molecular mechanisms of neurodegenerative disease—including Alzheimer’s, ALS, frontotemporal dementia, Parkinson’s, and multiple sclerosis—through high‑resolution interrogation of human models and tissue. The Senior Research Associate II will develop and deploy human iPSC‑derived cellular models and CRISPR‑based functional genomics to interrogate TDP‑43 biology and other priority pathways, building assays that drive internal discovery programs and partnering with computational biologists, neuropathologists, and program teams to translate cellular insights into actionable drug‑discovery hypotheses. Main Responsibilities Maintain, expand, and quality‑control human iPSC lines; generate and validate isogenic disease‑relevant lines using CRISPR/Cas9, base editing, and prime editing (knock‑in, knock‑out, tagged reporter alleles). Differentiate iPSCs into disease‑relevant CNS cell types—microglia, astrocytes, oligodendrocyte‑lineage cells, motor and cortical neurons—using established and emerging protocols; develop and optimize co‑culture and tri‑culture systems as needed. Build and validate fit‑for‑purpose cellular assays to interrogate TDP‑43 biology and other priority mechanisms, including cryptic exon readouts (STMN2, UNC13A, HDGFL2), TDP‑43 mislocalization and aggregation, cellular stress responses, and disease‑relevant functional endpoints. Develop high‑content imaging and plate‑based assays (96‑ and 384‑well formats) suitable for compound screening, target validation, and mechanism‑of‑action studies; partner with screening and ADME groups to qualify assays for internal use. Apply AI/machine‑learning based image analysis approaches for cellular phenotyping and high‑content readouts in partnership with computational team members. Contribute to the design, execution, and analysis of pooled and arrayed CRISPR screens (CRISPRko, CRISPRi, CRISPRa) in iPSC‑derived models, handling library preparation, lentiviral packaging, transduction, FACS‑ or imaging‑based selection, and single‑nucleus RNA and ATAC‑seq sample preparation. Generate and maintain stable cell lines, lentiviral reporter systems, and inducible expression systems to support discovery programs. Maintain rigorous electronic lab notebook records, contribute to internal data reviews, present results at group and cross‑functional meetings, and contribute to publications, posters, and patent filings. Develop, optimize, and document standard operating procedures; train junior team members on established assays and platforms. Coordinate with external academic collaborators and CRO partners on cell line generation, screen execution, and assay transfer. Education BS with 4+ years OR MS with 2+ years of relevant laboratory experience in stem cell biology, neuroscience, molecular biology, cell biology, or a related discipline. Experience & Technical Skills Hands‑on proficiency in human iPSC culture, banking, karyotype/STR/pluripotency QC, and directed differentiation into at least one CNS cell type (microglia, astrocytes, oligodendrocyte‑lineage cells, or neurons). Experience developing plate‑based and/or high‑content imaging assays, including assay miniaturization, Z‑factor and reproducibility assessment, and basic statistical interpretation of phenotypic data. Familiarity with high‑content imaging platforms (Opera Phenix, ImageXpress, IN Cell, Yokogawa CV8000) and image analysis tools (Harmony, Columbus, CellProfiler, QuPath). Experience with CRISPR/Cas9 genome editing in human iPSCs: guide design, delivery (RNP, lentiviral, or transfection), clone isolation, and validation of edited lines. Direct experience executing pooled or arrayed CRISPR screens, including library handling, transduction, selection strategy, NGS sample preparation, and first‑pass analysis (MAGeCK or comparable tools). Working knowledge of R or Python sufficient to perform QC, generate exploratory plots, and interface with computational collaborators. Familiarity with AI/machine‑learning based image analysis for cellular phenotyping. Experience with CRISPR activation/interference systems. Prior pharmaceutical or biotechnology industry experience and exposure to GLP/GxP‑adjacent documentation practices. Co‑authorship on peer‑reviewed publications. Soft Skills Strong organizational skills, meticulous record‑keeping, and ability to manage multiple parallel workflows in a deadline‑driven environment. Excellent written and verbal communication; comfortable presenting data to scientific audiences. Preferred Qualifications Experience with co‑culture, tri‑culture, or organoid systems modeling neuron–glia interactions. Background in neurodegenerative disease research, particularly TDP‑43 proteinopathies, ALS, FTD, or related disorders. Experience with CRISPR activation/interference systems. Experience with AI/machine‑learning based image analysis. Co‑authorship on peer‑reviewed publications. Benefits Health and well‑being programs, including high‑quality health care and prevention initiatives. At least 14 weeks gender‑neutral parental leave. Comprehensive benefits package that supports career growth and personal well‑being. Equal Opportunity & Anti‑Discrimination Statement Sanofi Inc. and its U.S. affiliates are Equal Opportunity and affirmative action employers committed to a culturally diverse workforce. All qualified applicants will receive consideration for employment without regard to race, color, creed, religion, national origin, age, ancestry, nationality, marital or domestic partnership status, sex, gender, gender identity or expression, sexual orientation, disability, veteran or military status, domestic violence victim status, genetic information or any other characteristic protected by law. #J-18808-Ljbffr Sanofi