Mechanotransduction in the bladder
Supervision:
Professor Jenny Southgate, University of York
Dr Dawn Walker, University of York
Professor Zhongmin Jin, University of Leeds
Many conditions affect bladder function and have devastating consequences for
quality of life. Common conditions include cystitis (painful inflammation of the bladder
which is usually caused by infection, but may also occur as a chronic condition with
no apparent cause), urinary incontinence (loss of bladder control, which is a
particular problem in the elderly) and bladder cancer (the fourth most common
cancer).
At present many of these conditions are intractable and any progress towards new
treatments (including tissue engineering) requires a better understanding of bladder
structure and functional relationships. Although the bladder is often thought of as a
hollow elastic organ that stores urine, this simplistic representation is far from the
truth. The bladder needs to be able to accommodate major changes in intravesicular
volume and surface area during filling/voiding cycles, without sustaining any
significant rise in pressure which would damage the kidneys. Understanding how
this is achieved in the bladder is a challenging multidisciplinary problem to integrate
the material and mechanical properties of the bladder with a cell/tissue biology
approach to understanding the mechanisms of mechano-sensation and transduction.
The project could be pursued along several single or combined approaches,
including investigating the mechanical/biological interface, using a cell culture
approach to examine the effects of mechanical stretch on second messenger release
and cell response, or developing a computational model of the system incorporating
finite element modelling of the mechanical environment with an agent-based model
of cell signalling and response.