A novel in-vitro 3-D cell culture model to study physiological mechanism of ageing in urothelial cells
Bladder dysfunction significantly reduces quality of life and is the only understudied of all currently highly prevalent age-related chronic diseases. Ageing is a significant factor for bladder diseases and our pilot study suggests an important role of the urothelium (bladder inner-lining) – the newly recognised sensory structure in bladder ageing. The study on physiological mechanism of ageing in urothelial cells is limited by lack of effective in-vitro models. This project aims to develop a novel in vitro model to accelerate the study by seeding native ageing urothelial cells on extracellular matrix scaffolding with 3-D growth.
Start date1 October 2020
The full fee will be covered at UK/EU rate
Stipend provided at UKRI rate per annum
Funding sourceDunhill Medical Trust ‘EMERGE’ Doctoral Training Programme
Bladder dysfunction significantly reduces quality of life and is the only understudied of all currently highly prevalent age-related chronic diseases. Ageing is a significant factor for bladder diseases and our pilot study suggests an important role of the urothelium (bladder inner-lining) – the newly recognised sensory structure in bladder ageing and ageing-associated bladder disorders. A major step forward is to understand cellular and subcellular mechanisms of ageing in urothelium from ageing bladders which necessitates the use of efficient in vitro models. A big challenge to study physiological mechanism of ageing in urothelial cells is the limitation of viable urothelial cells from ageing bladders and the short time window to catch a large variety of cellular activities. This project aims to develop a novel in vitro model to accelerate the study by seeding native ageing urothelial cells on extracellular matrix scaffolding with 3-D growth, providing physiologically relevant environment. The project will first set up and validate this in vitro model of 3-D cell culture with native mammalian urothelial cells and then demonstrate that the urothelial cells in this model possess basic physiological functions of their native counterparts. The study next will show that urothelial cells from the model retain the key ageing-dependent features of urothelial cells from in vivo ageing mice. Finally, extensive investigations will be conducted using this model to discover age-dependent changes in urothelial cell activities and cell signalling and to identify the underlying cellular mechanisms and molecular basis.
The project will provide excellent training opportunity. A variety of state-of-art physiological and molecular techniques will be used in combination with tissue engineering approaches. The student will develop the ability to innovate in biomedical research with personal development as an independent scientist. There will also be interactions with multi-disciplinary research teams and opportunities for international collaborations and national and international conferences.
Supervisor Dr Richard Wu has extensive research experience in bladder cell physiology and pathophysiology and ageing research with international reputations. Dr Wu has successfully led several major national and international research projects in bladder and ageing research and has a track record in supervising PhD students.
Supervisor Dr Kamalan Jeevaratnam is an established medical scientist with international reputations. His research interest includes integrative physiology, novel therapeutic agent discoveries, human animal interface research as well as medical education. One of his current research directions is to develop new in-vitro models to facilitate ageing research. Dr Jeevaratnam is a keen educator and has extensive experience in supervising PhD students.
- BSc degree or European equivalent degree in a relevant scientific or biomedical discipline (candidates with a medical or veterinary background need not have an MSc)
- Excellent communication and organisational skills
- Ability to work independently and as part of a team
- Experience with basic molecular techniques and physiological measurements
Previous research publication track record
IELTS requirements: IELTS overall score of 7, with at least 6.5 in all the components.