Determination of the changes in the regulation of nitrergic signalling in the ageing bladder

I. Scientific excellence
The prevalence of bladder diseases significantly increases with age, with one third of adults over 65 suffering from urinary incontinence. Although incontinence is not life threatening, it can often lead to significant anxiety, social isolation and a loss of dignity. Regulation of normal bladder function is through complex interplay of transmitters released from the nerves and lining (urothelium) of the bladder; with one transmitter – nitric oxide (NO) – shown to be a key regulator of function. The role of NO in ageing remains to be established. The supervisory team have previously shown the ability to monitor NO with sensor devices, explore changes in bladder function with disease and how bladder disorders are managed in the elderly and therefore best placed to support the student.

II. Clear aim and hypothesis
Our hypothesis is that nitrergic signalling mechanisms are reduced with age, leading to a loss in the regulation of bladder contractility that presents as age-related bladder dysfunction. Our aim is to explore how nitrergic signalling is altered with age in the bladder though a variety of methodologies.

III. Methodology and innovations
The student will develop a novel flexible sensor that can be utilised to measure real-time NO release during contractility studies in a mouse model of ageing (colony present at University of Brighton), where the role of current therapies will be explored. We will conduct biochemical assays to further characterise the mechanism, where the level and expression of enzymes and molecular targets of NO in young and old bladder will be measured. These studies will be translated to characterise the ageing human bladder, where identical measurements on shed cells present in patients’ urine will be conducted. The student will correlate findings with clinical measures to study bladder function, the potential influence of medication and the control of this process by the brain, which will be obtained by the supervisory team.

IV. Strategic relevance
An increasingly ageing human population is a major societal challenge and this proposal aims to understand how bladder function is lost with age. Our proposal brings together a strong interdisciplinary and translational research team who will foster strong collaborative links with external industrial and international partners, that will provide a vibrant environment for the development the postgraduate student.

V. Interdisciplinarity and fit with relevant DTA programme
This project brings together three members of the Alliance in an interdisciplinary, translational team who have expertise in bioengineering (Patel), pharmacology and physiology (Young) and an ECR clinical pharmacist specialising in the healthcare of the frail elderly (Barnes). The team will be supported by a urogynaecologist (Smith) with extensive experience of working with elderly incontinent patients. This proposal links strongly with the DTA programme in Applied Biosciences which is committed to healthy ageing and exposes the student to the challenge of drug development through mentorship from our external pharmaceutical industry collaborator (Ferring).

Applications

Applicants must apply using the online form on the University Alliance website at https://unialliance.ac.uk/dta/cofund/how-to-apply/. Full details of the programme, eligibility details and a list of available research projects can be seen at https://unialliance.ac.uk/dta/cofund/

The final deadline for application is Monday 8 October 2018. There will be another opportunity to apply for DTA3 projects in the spring of 2019. The list of available projects is likely to change for the second intake.