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
Mechanisms Underlying The Generation Of Spontaneous Contractions In Human Uterine Muscle: Potential Therapeutic Target For Dysfunctional Labour
Funder
National Health and Medical Research Council
Funding Amount
$496,901.00
Summary
Successful labour outcome is critical for the health of mother and offspring. Contractions too soon, or when they fail during labour, have significant short and long term consequences for mother and baby. Our recent studies on tissue from women in labour suggested new possible mechanisms underlying the initiation of uterine contractions. We will now test these ideas with a view to identifying new therapeutic targets for manipulating labour contractions.
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.
Integrating Biology And Medicine To Develop 3D-structure Guided Drug Design For Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$978,832.00
Summary
Calcium channel inhibitors are commonly prescribed for the treatment of heart disorders such as angina, hypertension, arrhythmias and hypertrophic heart disease. This class of drugs is one of the leading causes of drug-related fatalities. The impediment to designing better drugs is a lack of understanding of the 3 dimensional (3D) structure of the calcium channel. We will enable for the first time a 3D structure blueprint for the design of safe and highly selective calcium channel therapeutics.
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.