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Precision Medicine DTP - Strategies for precision gene therapy in the central nervous system


College of Medicine and Veterinary Medicine

About the Project

Industrial partner: Askbio Europe

Background

Many neurodegenerative disorders that are candidates for gene therapy involve pathology that is restricted to specific nervous system cell types. The possibility to develop vectors that distinguish cell types therefore provides a route to specific gene therapy approaches with minimal off-target effects. However, our current limitations in our ability to determine which cell types to target, to target them with sufficient specificity and to efficiently evaluate specificity of targeting are major obstacles to progress.

The project will involve collaboration between Askbio and University of Edinburgh (UofE), with an overarching goal of removing long-standing obstacles to efficient identification of gene therapy vectors capable of targetting specific cell types in the central nervous system. This builds on fundamental challenges identified during an existing collaboration between Askbio and the host lab. It will take advantage of expertise within the host lab in brain wide and high resolution anatomical and genetic approaches to analysis of neural circuits, and on Askbio expertise in informatics and promoter design. The project will focus on neuronal cell types involved in Alzheimer’s disease (AD). Key questions include how can these neurons be best distinguished from neighbouring neurons and from neurons in other brain areas? Are differences categorical or continuous? How can we most efficiently leverage markers of cell types differences to screen candidate vectors for gene therapy?

Aims

The focus will be on delineation of cell types involved in AD, on development of strategies for efficient assessment of candidate gene therapies to target these cell types and on evaluation of gene therapy strategies developed by Askbio, the industrial partner. The UofE component will focus on delineation of transcriptomically designed cell types in brain regions that degenerate early in AD and on developing efficient approaches for evaluation of specificity of gene therapy vectors. The Askbio component will focus on identification of gene therapy vectors that specifically target cell types that play important roles in AD.

Training outcomes

The project will provide training in state-of-the-art precision gene therapy approaches for nervous system disorders. Technical training will include wet lab experience in spatial transcriptomics, single cell transciptomics, whole-brain imaging and micro-circuit analysis, and dry lab experience in bioinformatics for gene expression analysis, promoter engineering and viral vector design.

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the link above.

For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine

Funding Notes

Start: September 2021

Qualifications criteria: Applicants applying for an MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualification, in an appropriate science/technology area. The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £15,285 (UKRI rate 2020/21).

Full eligibility details are available: View Website

Enquiries regarding programme:

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