Senior Scientist/Associate Director, Target Validation (Neurology)
London, on-site
We are partnered with an exciting Neuro TechBio start-up, currently operating in stealth, based in the heart of Central London. The company is developing a full-stack platform for neurodegenerative drug discovery, spanning target identification, validation, and biomarker development. Its technology addresses a fundamental bottleneck in the field: the lack of routine access to living human brain tissue. Backed by leading venture capital firms, the company has secured significant funding to advance both its proprietary platform and its Alzheimer’s disease target pipeline.
About this role
As Senior Scientist/Associate Director, Target Validation, you will be the lead scientist translating computationally derived target hypotheses into functional biology evidence. Working closely with ML engineers and computational biologists, you will receive platform derived multi-omic target packages, understand the biological hypothesis they encode, and design and execute cell perturbation experiments that validate efficacy and mechanism of action. This role combines hands-on execution and immediate line management responsibility, with the opportunity to build your own Target Validation team in line with company growth.
You will establish iPSC-derived neuronal and glial models of neurological diseases, in which you will use siRNA/CRISPR-based functional genomic approaches to interrogate target biology. You will generate and interpret transcriptomic and proteomic readouts to build mechanistic understanding of how target perturbation affects disease-relevant cellular phenotypes. Feeding findings back into the computational platform, closing the hypothesis-functional biology loop that transforms the proprietary target discovery engine from linear outputs to iterative biological design.
What you will do
Computational Target Interpretation & Experimental Design/Execution
- Receive computational target packages from the Platform team and critically evaluate functional genomic evidence, multi-omics integration results, and prioritisation rationale.
- Translate computational hypotheses into experimentally testable research questions - defining cellular model system, perturbation strategy, readout, and success criteria for each target.
- Participate in target review meetings, providing experimental feasibility input and challenging computational assumptions/outputs based on biological knowledge.
- Contribute to target prioritisation decisions by providing experimental perspective on tractability, model system relevance, and expected timeline to meaningful data.
iPSC-Derived Neuronal & Glial Disease Modelling
- Maintain, differentiate, and characterise iPSC-derived cell lines relevant to Alzheimer's disease: neuronal, astrocytes, microglia, and co-culture systems as appropriate.
- Develop and qualify disease relevant phenotypes as target biology demands, drawing on established literature and in-house expertise.
- Apply disease-relevant stressors, genetic variants, and cellular perturbations to model the mechanistic contexts in which target biology operates.
- Maintain rigorous quality control of iPSC lines including karyotyping, identity verification, and pluripotency / lineage characterisation to ensure reproducibility.
CRISPR Functional Screening & Perturbation
- Design and execute CRISPR-based perturbation experiments - knockout, CRISPRi, CRISPRa to interrogate the functional role of computationally nominated targets.
- Develop and implement pooled or arrayed CRISPR screening approaches to interrogate multiple targets or regulatory elements in parallel where throughput demands it.
- Validate perturbation efficiency at both DNA and RNA/protein level, establishing appropriate control conditions to ensure experimental rigour.
- Design screening readouts that capture disease-relevant phenotypes: transcriptomic shifts, protein aggregation, synaptic markers, inflammatory signatures, or epigenetic state changes.
Platform Integration & Cross-Functional Communication
- Work closely with the Platform team to ensure experimental findings are captured in a form that updates and refines computational models - closing the wet lab to algorithm feedback loop.
- Contribute to experimental data capture in in-house management system, maintaining records to the standard required for a drug discovery programme.
- Present experimental findings clearly to a mixed computational and scientific audience, including at external partner/advisor meetings or in due diligence contexts.
- Contribute to publications and patent filings where appropriate.
Required skills and experience
- PhD in neuroscience, cell biology, functional genomics, or related discipline + 4-6 years of post-doctoral or equivalent industry experience. Biotech/pharmaceutical contexts preferred.
- Hands on expertise in iPSC culture and disease modelling in neuronal or glial cell types.
- Hands on experience with siRNA and or CRISPR-based functional approaches in human cell models: knockout, CRISPRi, or CRISPRa.
- Experience in Alzheimer's disease or a closely related neurodegenerative condition - you understand disease biology at depth to design experiments that elucidate mechanistic detail.
- Accomplished with transcriptomic approaches (bulk RNA-seq minimum; single-cell desired) and ability to engage meaningfully with interpretation of computational analysis.
- Excellent communication and presentation skills, with the ability to convey complex concepts to diverse audiences.
- Exceptional problem-solving, critical thinking, detail handling, and organisation skills.
- Familiarity with ELN systems (Benchling preferred) and innate high documentation standards.
- Experience in molecular biology laboratory management and operations.
Highly Desirable
- Pooled CRISPR screening, including library design, screen execution, sequencing.
- Experience contributing to target assessment packages and go/no-go decisions in biotech/pharma drug discovery pipelines.
Interested? Apply and we will be in touch!