Student research project
This project will assess the protective effect of novel antioxidant and anti-inflammatory compounds on the development of artery disease in a diabetic setting.
Diabetic patients are 2–4 times more likely to suffer from cardiovascular disease leading to heart attacks and/or stroke. Understanding the mechanisms leading to increased vessel damage and atherosclerosis has been a major focus of our laboratory.
We have shown that compromised antioxidant defences, together with the increased production of reactive oxygen species (ROS), drives oxidative stress that accompanies diabetic atherosclerosis. We therefore consider the bolstering of the cell’s endogenous antioxidant defences as an important and superior strategy to vitamin therapy that has not held up to its promise in clinical trials to lessen heart disease. Nrf2 is the major regulator of oxidative stress and bolstering its function is known to lessen oxidative stress.
This project will investigate novel small molecules that have shown Nrf2 on-target activation as well as anti-oxidant and anti-inflammatory potential. Mechanistic analysis of its action will be studied in cultured vascular cells, including its impact on cellular metabolism. The protective effect of Nrf2 activators on atherosclerosis will be investigated in diabetic mouse models after several weeks of drug administration.
This project is suitable for a PhD, Honours or Masters student and will use various techniques, including:
- in vivo models of diabetic vascular disease
- cell culture
- assessment of endothelial cell function (inc. mitochondrial function by Seahorse Bioanalyser)
- gene silencing
- RNA isolation and qRT-PCR
- protein isolation and Western blotting
- en face plaque analysis