Research Scientist

Singleton Bio is an early-stage therapeutics company using generative AI models of human tissue to discover therapeutic targets in immunological and inflammatory diseases. Our mission requires strategic thinking, nimbleness, and deep expertise in several areas including computational biology, immunobiology, in vitro and in vivo pharmacology. This new startup company is recruiting for talented, experienced, and passionate individuals who are looking to meaningfully contribute to the creation of new medicines. Our Cell Interaction Foundation Model (CIFM) or “virtual tissue model” platform is a geometric graph neural network trained on spatial genomics data from millions of human cells. Built on more than a decade of virtual cell and tissue modeling research, the model learns the relationship between a cell’s expression state and its tissue microenvironment, and is used to simulate how tissue responds to perturbations at scale. Singleton is a fast-paced, dynamic environment where teammates will have broad exposure to the intersection of artificial intelligence-driven tissue models and drug development. We are rapidly building the Company and are looking for scientists to join us on this mission. Singleton Bio, located in South San Francisco, CA, is seeking an exceptional individual to join our team as a Research Scientist. About Singleton Bio Singleton Bio is an early-stage therapeutics company using generative AI models of human tissue to discover therapeutic targets in immunological and inflammatory diseases. Our mission requires strategic thinking, nimbleness, and deep expertise in several areas including computational biology, immunobiology, in vitro and in vivo pharmacology. This new startup company is recruiting for talented, experienced, and passionate individuals who are looking to meaningfully contribute to the creation of new medicines. Our Cell Interaction Foundation Model (CIFM) or “virtual tissue model” platform is a geometric graph neural network trained on spatial genomics data from millions of human cells. Built on more than a decade of virtual cell and tissue modeling research, the model learns the relationship between a cell’s expression state and its tissue microenvironment, and is used to simulate how tissue responds to perturbations at scale. Singleton is a fast-paced, dynamic environment where teammates will have broad exposure to the intersection of artificial intelligence-driven tissue models and drug development. We are rapidly building the Company and are looking for scientists to join us on this mission. Singleton Bio, located in South San Francisco, CA, is seeking an exceptional individual to join our team as a Research Scientist. Position Summary We are seeking a hands-on Research Scientist to help build out Singleton Bio's lab-based capabilities, including cell- and tissue-based assays to experimentally validate virtual tissue model outputs. These assays involve genetic and pharmacologic perturbation studies with mechanistic and phenotypic readouts that feed back into the model. Singleton Bio's focus is in autoimmune and chronic inflammatory disease, where much of the relevant biology plays out between immune cells and the stromal and parenchymal cells around them. This is a bench-heavy role for someone who is energized by novel targets and biology, and who is comfortable working in both immortalized lines and primary cells, including primary immune cells. Key Responsibilities Partner with the computational team to translate virtual tissue model outputs — cell type–specific expression, ligand–receptor inference, disease-associated microenvironments — into concrete, testable in vitro hypotheses. Select, qualify, and run cell and tissue models to validate targets by genetic knockdown or overexpression and by pharmacologic perturbation, with expression profiling, flow cytometry, and soluble readouts (MSD, Luminex, ELISA). Design and run multi-color flow cytometry assays to immunophenotype primary human immune cells, and use FACS to isolate or enrich defined cell populations for downstream studies. Establish and document 96- and 384-well assay performance: Z′-factor, signal window, %CV, edge effects, dose–response (EC50/IC50) reproducibility, vehicle tolerance, and passage- or donor-dependent drift. Author protocols, SOPs, and assay qualification reports that transfer cleanly to colleagues and CROs. Perform routine aseptic mammalian cell culture: maintenance, passaging, cryopreservation, thaw and recovery, and expansion of adherent and suspension immortalized lines and primary cells. Establish and maintain more complex models as needed, typically incorporating immune cells: Transwell cultures, 3D spheroid and organoid systems, and tissue-relevant matrices. Own the practical challenges of adding immune cells to these systems, including donor matching, viability over the culture period, and recovering cells for downstream readouts such as flow cytometry. Analyze data with appropriate curve fitting, normalization, and statistics. Maintain a complete, contemporaneous electronic laboratory notebook, and ensure data integrity and traceability from raw file to reported number. Manage relevant external work at CROs and tissue vendors: protocol transfer, donor sourcing, data review, and troubleshooting. Present analyses to leadership, partners, and investors clearly and rigorously. Contribute to scientific strategy, publications, and patents. Help hire and mentor future members of the laboratory team. Qualifications Required Ph.D. in cell biology, immunology, biochemistry, pharmacology, or a related field with 1–4 years of post-doctoral or industry experience; or M.S./B.S. with 6+ years of industry experience. Direct experience in autoimmune and/or chronic inflammatory disease therapeutic areas. Aseptic mammalian cell culture expertise, including banking and QC, and direct experience with primary human cells including primary immune cells. Multi-color flow cytometry with human immune cells - panel design, compensation, controls (FMO, viability), gating, and analysis in FlowJo or equivalent. Immune functional assays - ex vivo whole blood, PBMC, or subset stimulation with multiplex cytokine readouts. Experience developing and qualifying a cell-based assay from concept to routine, documented method — not solely executing established protocols. Genetic (siRNA, shRNA, CRISPR, overexpression) and pharmacologic perturbation with appropriate controls and expression or target engagement confirmation; fluency in dose-response analysis and assay statistics. Proficiency across several of: multimode plate readers, high-content imaging, immunoassays (ELISA/MSD/Luminex/AlphaLISA), Western blot, and qRT-PCR. Meticulous documentation habits; comfort with an electronic lab notebook. Excellent written and verbal communication skills, including presenting complex results to non-specialist audiences. Preferred Isolation of primary cells from human tissue (dissociation, sorting, enrichment) and work with consented clinical or surgical material. Preparation of high-quality RNA from cell and tissue samples in support of RNA-seq and scRNA-seq. Orthogonal target-expression validation in tissue - IHC, IF, RNAscope and in situ hybridization. Experience with complex Transwell, co-culture, and tissue-based in vitro models that incorporate immune cells. Experience with fibrosis-relevant in vitro models, such as fibroblast activation or myofibroblast differentiation assays. Protein expression methodologies (CHO, E. coli, cell-free transcription and translation), protein purification, and biochemical characterization (Octet, SPR). Liquid handling automation and 384-well screening. Data analysis in Python or R; comfort with Prism, FlowJo, Genedata, Dotmatics, Spotfire, and ELN/LIMS. #J-18808-Ljbffr