Cellular Mechanisms Of Pacemaking In The Upper Urinary Tract: Effects Of Sensory Neuropeptides And Prostaglandins
Funder
National Health and Medical Research Council
Funding Amount
$80,680.00
Summary
The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of thei ....The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of their lifetime, with men being 2-4 times more likely than women to have calculi. Pain management of renal colic usually involves the prescribing of strong analgesics, and antispasmodic and nonsteroidal anti-inflammatory agents. Most stones are expelled spontaneously if they are small. Larger stones require interventions such as fragmentation (extracorpereal lithotripsy), which is an out patient procedure, or physical removal, using ureterscopes or endoscopes or open surgery under general anesthesia; procedures usually requiring hospital stays of 2-7 days. This project will provide valuable information on the mechanisms by which sensory nerves and endogenous prostaglandins control motility in the mammalian UUT. In particular, these studies will contribute to the search of specific anti-inflammatory agents which will affect particular aspects of UUT motility. A clearer understanding of the cellular origin of UUT rhythmicity will lead to more informed non-surgical interventions to encourage the passing of painful calculi. Such information will also aid in the treatments of other forms of renal colic, during ureteric obstruction, and urinary tract infection. Ureteric stasis is an important condition to avoid, if left untreated permanent kidney damage usually occurs within 6 weeks.Read moreRead less
The Effects Of Human Epilepsy Mutations On Synaptic GABA-A Receptors Studied By Localization-based Superresolution Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$524,215.00
Summary
The genetic epilepsies are debilitating neurological disorders that are frequently associated with mutations in genes encoding neurotransmitter-gated receptors in the brain. The goal of this project is to understand mechanisms that cause changes in neuronal communication and lead to epilepsy on a single receptor level. This will lead to an improved understanding of the mechanisms of epileptogenesis and new insights into ways of treating different epilepsies.
Mechanotransduction is defined as the ability of living cells to respond to and convert mechanical stimuli into electro-chemical cellular signals to ensure survival. It is largely dependent on membrane proteins known as mechanosensitive (MS) ion channels. These channels are involved in senses of hearing and touch, and are also crucial regulators of heart and muscle function. This research aims to elucidate the general physical principles underlying mechanotransduction in living cells.
Learning And Network Plasticity In A Primitive Sensory Cortex
Funder
National Health and Medical Research Council
Funding Amount
$461,557.00
Summary
Our brain is a uniquely powerful supercomputer, in part because it is ‘plastic’ -- that is, it can change itself when we adapt or learn something new. An understanding of the causes of brain plasticity is an essential part of any quest to understand the brain in sickness and in health. This research uses a laser microscope to ‘read the minds’ of mice as they learn about odours. By observing plasticity in action, we will gain deeper insights into normal brain function.
Unravelling Mechanotransduction Pathways In The Heart
Funder
National Health and Medical Research Council
Funding Amount
$949,956.00
Summary
This project addresses the still unresolved question of involvement of mechanosensitive ion channels in heart hypertrophy and arrhythmias including ventricular arrhythmias. These pathological conditions are a cause of a broadening fiscal healthcare burden in Western societies. Consequently, investigating the role of this class of ion channels in heart disease presents a priority for medical science and a great opportunity to improve the health outcomes for the Australian people.
Neural Basis Of The Functions Of The Primary Visual Cortex: Roles Of Feedforward And Intracortical Inputs
Funder
National Health and Medical Research Council
Funding Amount
$486,280.00
Summary
Signals from the eyes undergo extensive processing at the level of the primary visual cortex so that basic features in the scene such as lines, edges, colours and movement are coded in the activity of individual neurones. This project aims to further our understanding of this process at the basic cellular level. This will not only enable interventions that would help those with poor sight but also give us an insight into basic brain circuitry and its derangement in many neurological disorders.