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Advanced Research Assistant: Neurodegenerative Disease Modelling using CRISPR

We are seeking a motivated Advanced Research Assistant to join an interdisciplinary team on an exciting and ambitious new project using cutting-edge techniques to study how genes associated with neurodegeneration contribute to disease in a cell-type-specific manner. We will perform targeted CRISPR screens in multiple disease-relevant cell populations derived from human induced pluripotent stem cells (hiPSCs) and assess the resulting phenotypes using a combination of single-cell RNA sequencing (scRNAseq) and high throughput cellular assays.

The positions will be based at Wellcome Sanger Institute under the leadership of Dr Andrew Bassett and Dr Leopold Parts, and at the University of Cambridge under the leadership of Dr Florian Merkle. This project forms part of the Open Targets collaboration between academic and industrial partners to identify new drug targets for the treatment of neurodegenerative disease.

The successful applicant for this position will work collaboratively with a two lab-based Postdocs and a Senior Bioinformatician. This team will first identify top candidate genes associated with neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s, Frontotemporal Dementia), build custom barcoded CRISPR libraries to knock out these genes in hiPSCs, and then differentiate them to neurons, astrocytes, and microglia using the latest methods. The resulting cellular phenotypes will be assessed by scRNAseq and cellular assays in tens of thousands of cells (e.g. based on FACS or high content imaging). Applicants will have the opportunity to employ well-established differentiation protocols and phenotyping assays, but also to develop or adapt new methods for unbiased screening or more detailed follow-up studies in arrayed screens. Our aim is to identify and prioritise genes important for disease-relevant processes across multiple cell types, to reveal the underlying molecular mechanisms and new routes for therapeutic intervention.

Overall, this project represents an exciting opportunity to leverage recent advances in stem cells, CRISPR, and single cell sequencing technologies to drive innovation in disease-relevant cell models, develop assays to measure neurodegenerative phenotypes, and apply them at scale using the facilities at the Sanger Institute to advance our understanding of these disorders. It offers an outstanding career development opportunity for a highly-motivated applicants. We encourage anyone with the Essential Skills to apply and especially welcome applications from individuals with expertise in the Ideal Skills listed.

Grade: 3 Salary per annum: 27,445 to 33,876 Full Time or Part Time: Full Time Contract Type: Fixed Term Contract Length: 3 years Reference:83923


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