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Alternative splicing in diabetic nephropathy (Self Funded)

  • Full or part time
  • Application Deadline
    Monday, September 16, 2019
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Project information:

Multiple molecular mechanisms of diabetic nephropathy (DN) progression have been described in recent years, however, mechanism-derived treatments for DN are still lacking. This is partly due to poor understanding of the detailed molecular mechanisms underlying diabetic complications. The standard of care is to control glycaemia but most of the time this does not stop the occurrence of the nephropathy.

There is therefore an increasing need to better understand molecular mechanisms of progression in DN as well as to develop novel treatments that target specifically these mechanisms and are able to slow progression of the underlying chronic kidney disease in DN. This project will be investigating novel mechanisms of progression in DN at the level of alternative splicing.

Alternative splicing (AS) has emerged in the post-genomic era as one of the main drivers of proteome diversity with at least 94% of multi-exon genes being alternatively spliced in humans. AS is therefore one of the main control mechanisms for cell phenotype, and a process deregulated in disease. Numerous reports describe pathogenic mutations in splice factors, splice sites or regulatory sequences; additionally, in many cases there is an abnormal proportion of splice isoforms (or novel isoforms) in disease compared to the physiological pattern, without an apparent driver mutation. It has therefore become essential to study how AS is regulated in physiology, how it contributes to pathogenesis and whether we can manipulate faulty splicing for therapeutic advantage. While the disease most commonly linked to deregulation of AS in several genes is cancer, there are many in-depth reports of pathogenic splice variants in diseases ranging from neuromuscular disorders to diabetes or cardiomyopathies.

Diabetic nephropathy is a major health problem in UK and worldwide and no specific treatment is known. This project will be investigating pathological variants of splicing isoforms in diabetic nephropathy models both in vitro and in vivo, with a view to unravel novel therapeutic targets

Funding Notes

This project is self funded. In terms of project costs, bench fees, of approximately £7000 without animal work; £10000 with animal work apply. Please contact Dr Oltean () for more information

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