MicroRNA regulation of insulin signalling in the podocyte. (360G-Wellcome-105728_Z_14_Z)
MicroRNAs (miRs) and intact insulin signalling are critical determinants of podocyte phenotype, and podocyte-specific deletion of miRs or insulin receptors results in histological changes resembling those seen in Diabetic Nephropathy (DN). I hypothesise that miRs regulate podocyte insulin sensitivity and can be manipulated to prevent DN. My preliminary work using insulin-resistant podocytes shows differential expression of 103 miRs, 6 of which I have selected for further study based on significa nce level, abundance and known targets within insulin-signalling pathways. I have three specific aims: 1. Manipulate candidate miRs in vitro to determine their role in podocyte insulin-signalling 2. Validate miR changes in vivo in a db/db mouse model of DN 3. Evaluate miR changes in the urine and renal biopsy tissues of patients with T2DM I will do this using techniques already established in the host laboratories and utilising appropriate animal models and patient samples which I have en sured are ready for me to start this fellowship (diabetic mouse with fluorescently-labelled podocytes via cre-lox technology and urine/biopsy samples from Wales Research Tissue Bank). This project will advance knowledge of a previously unexplored aspect of podocyte/miR biology that has translational potential in therapeutic miR modulation and biomarker development.
Where is this data from?
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Grant Details
| Amount Awarded | 218298 |
| Applicant Surname | Wonnacott |
| Approval Committee | Clinical Interview Committee |
| Award Date | 2014-11-13T00:00:00+00:00 |
| Financial Year | 2014/15 |
| Grant Programme: Title | Research Training Fellowship |
| Has the grant transferred? | No |
| Internal ID | 105728/Z/14/Z |
| Lead Applicant | Dr Alexa Wonnacott |
| Planned Dates: End Date | 2020-03-13T00:00:00+00:00 |
| Planned Dates: Start Date | 2016-06-14T00:00:00+00:00 |
| Recipient Org: City | Cardiff |
| Recipient Org: Country | United Kingdom |
| Region | Wales |
| Research conducted at multiple locations? | No |
| Sponsor(s) | Prof Donald Fraser |
| Total amount including partnership funding | 218298 |