AI-Enabled iPSC Disease Modeling & Functional Genomics

Sanofi•Cambridge, MA

1d•Hybrid

About The Position

Sanofi is building a next-generation neuroscience research engine focused on defining the molecular mechanisms of neurodegenerative disease — Alzheimer’s disease, ALS, frontotemporal dementia, Parkinson’s disease, and multiple sclerosis — through high-resolution interrogation of human models and tissue. We are seeking a Senior Research Associate II to develop and deploy human iPSC-derived cellular models and CRISPR-based functional genomics to interrogate TDP-43 biology and other priority pathways, and to deliver fit-for-purpose assays that drive internal discovery programs. This role sits at the experimental engine of the group. The successful candidate will design, generate, and characterize isogenic iPSC lines and iPSC-derived glial and neuronal cultures; build robust phenotypic assays suitable for hit-finding and target validation; and contribute to pooled and arrayed CRISPR screens that uncover genetic modifiers of disease-relevant phenotypes. The role partners closely with computational biologists, neuropathologists, and program teams to translate human cellular insights into actionable drug discovery hypotheses. Join the engine of Sanofi’s mission — where deep immunoscience meets bold, AI-powered research. In R&D, you’ll drive breakthroughs that could turn the impossible into possible for millions.

Requirements

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.
Demonstrated 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).
Hands-on 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 (e.g., Opera Phenix, ImageXpress, IN Cell, Yokogawa CV8000) and image analysis tools (Harmony, Columbus, CellProfiler, QuPath).
Strong organizational skills, meticulous record-keeping, and the ability to manage multiple parallel workflows in a deadline-driven environment.
Excellent written and verbal communication; comfort presenting data to scientific audiences.

Nice To Haves

Experience with co-culture, tri-culture, or organoid systems modeling neuron–glia interactions.
Hands-on experience with CRISPR/Cas9 genome editing in human iPSCs, including 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 using MAGeCK or comparable tools.
Background in neurodegenerative disease research, particularly TDP-43 proteinopathies, ALS, FTD, or related disorders.
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.

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, and tagged reporter alleles).
Differentiate iPSCs into disease-relevant CNS cell types — including microglia, astrocytes, oligodendrocyte-lineage cells, and 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 (e.g., 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, including library handling, lentiviral packaging, transduction, FACS- or imaging-based selection, and single nuclei 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.