Research Associate (Fixed Term)
We are seeking a Research Associate to study how genes associated with obesity contribute to disease in a cell-type-specific manner to support the development of novel therapeutics. Briefly, we will perform targeted CRISPR screens in 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), high throughput cellular assays, multi-'omics integration. The position will be based in the laboratory of Dr. Florian Merkle ( ) at the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge and will be supported by an interdisciplinary team with expertise in developmental and stem cell biology, neuroscience, gene editing, disease modelling, genomics, and bioinformatics.
Obesity is common and highly heritable disease of the brain. In particular, cell populations in the hypothalamus are critically important for regulating food intake and their dysfunction leads to the abnormal regulation of body weight. Hundreds of obesity-associated genes have been identified, but for most of them the molecular and cellular mechanisms linking genotype and phenotype are unknown. To address this problem, we will work collaboratively with bioinformaticians to identify top candidate genes, build custom barcoded CRISPR libraries to knock out these genes in hiPSCs, and then differentiate them to appetite-regulatory neurons. 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). The successful applicant will have the opportunity to leverage well-established differentiation and phenotyping assays, but also to develop or adapt new methods for unbiased screening or more detailed follow-up studies in arrayed screens. Our ultimate aim to reveal molecular disease mechanisms that could be therapeutically targeted.
The position is funded by the New York Stem Cell Foundation ( ), enabling the successful applicant to join a world-class international network to tackle major challenges in human health. Overall, this project represents and outstanding career development opportunity for a highly-motivated applicants. It is essential that applicants have a PhD in Neuroscience, Cell Biology, Molecular Biology, or a closely related field and meet all the other criteria as detailed in the further particulars.
Informal inquiries about this position should be directed to Florian Merkle at with reference number RG22562 in the subject line.
This position is based at the Wellcome Trust-MRC Institute of Metabolic Science ( ) at the University of Cambridge, which provides a highly collaborative and stimulating environment. Our group is affiliated with the Cambridge Stem Cell Institute ( ) and we collaborate closely with groups at the WT-Sanger Institute ( ), the Open Targets academic-industrial partnership ( ), and the UK Dementia Research Institute (UKDRI, ).
Fixed-term: The funds for this post are available for 24 months in the first instance.
Once an offer of employment has been accepted, the successful candidate will be required to undergo a security check.
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Closing Date: 21st July 2020
Please quote reference RG22562 on your application and in any correspondence about this vacancy.
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