Senior Computational Biologist

Are you ready to own the analysis, predictive modeling and interpretation of large-scale perturbation single-cell transcriptomic screens, turning high-dimensional, complex gene expression state changes into clear biological conclusions that drive therapeutic decisions in cardio-renal-metabolic disease? Large-scale transcriptomic data is at the heart of Gordian’s discovery efforts, and the company will succeed based on our ability to accurately predict physiological changes in disease using single cell gene expression as a readout. In this role, you’ll help ensure our screening and validation decisions are grounded in rigorous, transparent and state-of-the-art analyses, enabling us to confidently prioritize the best targets and interventions. The Destination: Gordian Biotechnology is a therapeutics company whose mission is to cure age-related disease and wake up every morning more capable than the day before. Traditional ex vivo screening methods have failed to produce effective treatments, as age-related diseases have complex causes that include interactions with the aged environment. To address this problem, Gordian’s platform is the first and only to enable pooled in vivo tests at scale, across different species of diseased animals reflecting patient profiles. We are able to deliver and test hundreds of therapeutics in individual animals, and scale efficacy testing to rapidly prioritize targets and interventions with a clear path toward development (more info on our website). We are running this discovery engine to ensure an abundance of therapeutic hypotheses can be tested for complex diseases, eventually mapping out the effects of every druggable target across many diseases, and advancing programs both internally and through collaborations with external partners. By working across related sets of indications, we can identify medicines with impacts on age-related multimorbidity. The Journey: Our mission is audacious, and the path will be full of both challenges and excitement. Two things characterize the Gordian experience: 1) We work as a team, with ownership in our own roles and trust in each other. 2) We strive for extraordinary outcomes, and in doing so grow our skills and capability. Team – Relying on each other begins with transparency. We set clear goals, visibly connecting individuals and teams to our company objectives. This empowers each of us to make autonomous decisions about our work, knowing how they will affect the bigger picture. Our communication happens out in the open. We give and receive feedback from a perspective of helping each other grow, share mistakes, and ask for help. Extraordinary – Every day, we ask ourselves ‘How could this process/outcome be even better?’. Knowing our overall mission, we do what we think helps us make the most progress, without asking for permission. We don’t shy away from big challenges or unknown territory, but find a way to excel. Our colleagues are amazing, both at what they do and as people. They inspire us to keep up, to not let them down, and be inspiring in return. Like any cutting-edge research environment, Gordian doesn't believe in a standard 9 to 5 day. We set ambitious project goals and support each other to meet them, while maintaining the balance individuals need to thrive and achieve excellence. Our team is geared towards helping each other out and maintaining a culture of intellectual and social fun. We like getting things done and keep standing meetings to a minimum. We have an unlimited vacation policy, not including major holidays. We unwind with weekly team lunches, and support each others’ projects both experimentally and by ‘pre-mortem’ meetings to discuss possible failure modes and experimental design. If this environment sounds appealing, help us bring it to life. We are at an exciting inflection point: applying our technology to create comprehensive atlases of therapeutic targets across multiple diseases, partnering for financial and intellectual support, and translating these insights into new medicines. We want both your ability and personality along for the ride. Our culture is a source of great pride; it represents both who we are and who we wish to be. And You: Your mission as a Computational Biologist at Gordian is to measure the impact of single-cell perturbations on transcriptomic state, and use those signals to predict changes in physiological state under therapeutic conditions. You’ll focus on cardio-renal-metabolic indications and relevant tissues (heart, kidney, adipose, liver, etc.), partnering closely with disease-area experts and experimental teams to translate screen results into clear, testable biological hypotheses. Working collaboratively with other computational members, you will guide key analytical decisions that shape how screens are designed, QC’d, interpreted, and ultimately used to help select hits for validation. This includes developing and applying robust approaches for handling heterogeneous contexts, confounders, and controls, communicating conclusions with high interpretability and generalizability, and ensuring the right context and outputs flow back to the single-cell team and disease experts to continuously improve data generation and troubleshooting. You’ll also integrate internal screen data with relevant public genomics resources to connect perturbation-driven molecular changes to in vivo physiology, identifying high-confidence features that capture desirable phenotypes, and build a prioritized set of candidate targets for future screens on the basis of those predictions. Over time, you’ll help establish and iterate on selection criteria for validation that improves screening efficiency and translatability across programs. In your first month, you’ll become fluent in our in-house pipelines and workflows and independently propose analysis tasks supporting our Obesity and Heart Failure programs, starting with resource gathering and structured data exploration. By three months, you’ll make significant contributions to feature development and/or validation, including evaluating alternative analytical approaches with appropriate use of controls, statistical testing, and an emphasis on interpretability tied to mechanism-of-action validation. At six months, you’ll help define strong positive and negative controls (indicators) for these screens, partner independently with disease experts on forward screen planning, and use existing validation comparisons to assess predictive power, proposing concrete improvements to analysis methodologies along the way. PhD in Bioinformatics, Computational Biology, or a related quantitative field. Recognized domain expert in computational biology with at least 2+ years of hands‑on experience analyzing single‑cell transcriptomic data (industry and/or postdoctoral) across different biological contexts, and a proven track record of productivity with at least one peer‑reviewed publication or pre‑print that includes a major contribution as a co‑author. Proactive and passionate about assessing new developments in the field including and not limited to single cell and functional genomics, human genetics etc., using appropriate tools for analysis applications in each case. Strong proficiency in both Python and R for single‑cell analysis (for example, Scanpy and Seurat) and general data analysis, with the ability to move fluidly between ecosystems and experience working on high performance clusters (AWS, GCL). Working knowledge of NGS workflows and common file formats (including FASTQ and BAM), with the ability to adapt or modify pipelines and communicate clear implementation requirements to infrastructure partners. Strong statistical foundations and judgment around controls, confounders, and interpretability, plus the ability to communicate results clearly through honest, high‑signal visualizations and concise summaries. Applies in‑depth knowledge to practical problem solving with a result‑driven mindset. High ownership, self‑motivation and strong cross‑functional communication skills, with a track record of partnering effectively with experimental teams and domain experts in a fast‑paced, ambiguous environment. Additional valuable skills if you have them Experience with pooled perturbation and screening data (for example, CRISPR or barcode‑driven screens) and single‑cell perturbation analysis methods. Prior work in cardio‑renal‑metabolic biology and relevant tissues (heart, kidney, adipose, liver), either directly or through close collaboration with disease experts. Experience integrating vast public genomics resources with internal data and building scalable workflows for large datasets (HPC and/or cloud). Experience with preclinical models for validation with functional readouts (e.g., in human explants, organoids, etc). The Details: G o rdian aims to provide everything you need to thrive. Beyond community and science, you’ll have enough equity to be a true stakeholder in the company, competitive salary, full health/dental/vision/life insurance, 401k with match, onsite lunch paid for 3 days a week, an onsite gym, whatever vacation you need to be at your peak, remote work flexibility, and access to world‑class mentors and advisors to support your professional growth. Our building is in the heart of the biotech capital of South San Francisco, and this position would hybrid/onsite. #J-18808-Ljbffr