The role of Nox enzymes in ageing bladder dysfunction – targeting specific ROS controlling molecules
We are looking for an enthusiastic student to join a major international collaborative research project to examine the role of a unique and targetable source of reactive oxygen species – Nox enzymes in the body in ageing and chronic pathological processes.
Start date1 October 2019
Funding sourceDoctoral College
Full-time tuition fee at UK/EU rate (£4260) and a stipend £15000 per annum.
Age-related diseases present huge health and societal challenge to our ageing society. One major highly prevalent (15-20% population) but most under-studied debilitating chronic ageing disease is overactive bladder disorder (OAB) with an annual cost £3.7 billion to NHS. Recently bladder mucosal lining (urothelium) is recognised as a new sensory structure and its dysfunction may underlie pathogenesis of OAB.
A major step forward is to identify its pathological mediators. Oxidative stress is a fundamental pathological mediator and ROS generating enzyme NADPH oxidase (Nox) is of particular significance as it is the only enzyme in our body that produces ROS as its sole function, thus offering the advantage of specificity over other enzymes as a drug target.
This project is part of a major international collaborative project and uses an integrated molecular and functional approach to examine how Nox-derived ROS mediates ageing bladder dysfunction and OAB, and to identify Nox subtype(s) as novel therapeutic target for OAB. We hypothesize that Nox-derived ROS and oxidative stress have a significant role in urothelial and bladder physiology and in dysfunction with ageing. Targeting Nox has therapeutic potential to improve bladder function. The overall aim of this collaborative project is to investigate the role of Nox enzymes and ROS in regulating bladder function and mechanisms of Nox activation in ageing bladders. We will first determine whether Nox enzymes exist in the urothelium and bladder; if so what subtypes they are; next whether these Nox subtypes are functional and their characteristics and which is the main functional subtype(s); we will then investigate how these Nox and associated ROS affect normal urothelium and bladder physiology and next how they contribute to urothelium and bladder dysfunction in response to ageing process; finally we will examine the mechanisms whereby these Nox pathways work at cellular and molecular levels.
This is the first study in the field. The novelties of Nox enzymes and the urothelium provide an enthusiastic PhD student with a stimulating opportunity to develop the ability for innovation, creativity and critical analysis. A large range of multidisciplinary approaches and methods will equipment the student with all-round research skills. This international collaboration, a large variety of expertise in the supervision team and collaborating institution as well as the opportunities to work in both Surrey laboratories and Temple University in US, provide excellent learning opportunity and research environment to train a PhD student to become an independent scientist in the future.
Dr Wu is an expert in bladder cell physiology and pathophysiology with international reputation. Dr Wu has led many research projects with several important discoveries in the field. His team has pioneered the area of the urothelium signalling and the new area of ROS regulation of urothelial and bladder function. He is the PI for the major 5-year grant from the BBSRC and NIH “Nox enzymes in ageing bladder dysfunction” on which this PhD project is based.
Dr Camelliti is a well-established scientist and has made her international name for live cardiac slices model, cell-to-cell communication and myofibroblast interaction with other cell types akin to bladder urothelial cell-suburothelial myofibroblasts interaction.
- Applications from UK and EU students only.
- A first-class degree in biomedical science and related areas
- English language requirements: IELTS overall score of 7, with at least 6.5 in all the components.