Regulation of urothelial and bladder function by oxidative stress – the role of Nox enzymes
Accepted candidates are required to pay standard tuition fees in addition to 20% of bench fees. Materials and consumables will be provided.
Funding sourceSelf-funded students only
Reactive oxygen species participate in normal cell function but excessive production of ROS and cause pathological damages to the tissue. Of several ROS generating enzymes, NADPH oxidase (Nox) family is the only enzyme that produces ROS as its sole function, thus offering the advantage of specificity over other enzymes as the drug target.
Bladder dysfunction is a major age-associated chronic disease and presents a major health and social challenge to our ageing society. The recent recognition of the urothelium – mucosal lining of the bladder, as a new sensory structure has significantly advanced our understanding of bladder function and pathogenesis. However, the role of ROS and Nox in bladder function, in particular, in urothelial function and bladder ageing, has never been examined. Our pilot study suggests a role of ROS and Nox enzymes in bladder function.
This is the first investigation into the role of ROS in regulating bladder function - part of a major project looking to bladder ageing funded by the BBSRC and NIH. The novelties of Nox enzymes and the urothelium provide an enthusiastic PhD student with a stimulating opportunity to address this highly significant scientific question. We will test the hypothesis that ROS and Nox are key regulators in urothelial and bladder function and Nox-derived ROS and oxidative damage contribute to ageing bladder dysfunction.
The project has three main objectives:
- To determine the enzymatic sources of ROS in the bladder urothelium and smooth muscle, and the contribution from Nox subtypes
- To assess the regulation of ROS production/Nox activation by bladder-related inflammatory mediators
- To determine the functional relevance of ROS/Nox activation in bladder function and contribution of Nox-derived oxidative stress to ageing bladders.
A set of important experiments will be performed to achieve these objectives. An integrated approach will be employed including biochemical assay, immuno-fluorescence, protein blotting, molecular techniques, physiological measurement and real-time calcium imaging. Nox subtype knockout models will also be used to gain molecular insight. The project will provide an excellent training opportunity for a PhD student. The outcomes will provide new insight into pathophysiology of ageing and identify new molecular targets which reduce oxidative damage to treat ageing associated bladder disorders.
Applicants should have:
- A first-class or upper second-class honours degree (or equivalent) in biomedical sciences, biological sciences, physiology or similar subjects.
How to apply
Applications must include:
- A cover letter
- Research statement
- Contact details of two academic references.