About the Project

Endothelial dysfunction is a unifying mechanism in diabetes, atherosclerosis and other chronic cardiovascular diseases. It is driven by oxidative stress and loss of nitric oxide (NO) bioavailability, particularly through oxidation of the essential eNOS cofactor tetrahydrobiopterin (BH4) to 7,8-dihydrobiopterin (BH2). This project will investigate N-hydroxy-L-arginine (NOHA), the natural intermediate in NO synthesis, as a novel redox-activated NO therapy.

The PhD will first define how NOHA behaves as a ROS scavenger and NO donor in vitro and in primary human aortic endothelial cells. It will then use quantitative proteomics to map the downstream endothelial signalling pathways modulated by NOHA under hyperglycaemic and inflammatory conditions. Finally, it will assess whether NOHA can restore endothelial function in advanced in vitro models.

The project will employ a range of techniques including cell culture, quantitative NO and ROS assays, HPLC-EC analysis of pterins, proteomics, Western blotting, angiogenesis and adhesion assays, and ECIS.