Diabetes mellitus is a major health problem, affecting 2.9million people in the UK alone. 40% of people with diabetes develop diabetic kidney disease (DKD); the commonest cause of kidney failure in UK. Development of novel treatments is hampered by a lack of understanding of what causes DKD and its progression. Previous work from the WKRU has shown that microRNAs (miRs) may have a pivotal role. MiRs act like a dimmer switch to control how much protein genes produce, and it has become apparent that they have widespread roles in human disease.
Research from our collaborating laboratory (Bristol) focuses on the podocyte, a sieve-like cell in the kidney. They have shown that insulin is critical to the proper functioning of this cell. When podocytes become resistant to insulin, changes in the kidney occur that mimic those seen in DKD.
This PhD project will combines the strengths of Bristol and Cardiff groups to seek to determine the role miRs play in the insulin response of the podocyte and how its disruption may lead to the changes seen in DKD. The knowledge gained will help identify new targets in the monitoring and treatment of DKD.
1. Determine which miRs change as mice develop diabetic kidney disease over time (db/db mouse model and in vitro cell models)
2. Determine the mechanism of miR-induced insulin resistance to direct future therapeutic targets in DKD
3. Evaluate the miR changes in the urine/renal biopsy samples of patients with DKD to establish biomarkers potential
Dr Alexa Wonnacott