Primary Cardiac Hypertrophy - A Functional Genetic Approach To Investigate Cellular Mechanisms Of Metabolic Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$226,692.00
Summary
Population studies have recently shown that enlargement of the heart, even when blood pressure is normal, is a risk factor which can lead to cardiovascular complications. Very little is known about the alterations in heart cell structure and function which occur in cardiac enlargement not complicated by high blood pressure. It is possible that specific metabolic abnormalities underlie this condition. The goal of this study is to use a newly developed genetically manipulated experimental animal m ....Population studies have recently shown that enlargement of the heart, even when blood pressure is normal, is a risk factor which can lead to cardiovascular complications. Very little is known about the alterations in heart cell structure and function which occur in cardiac enlargement not complicated by high blood pressure. It is possible that specific metabolic abnormalities underlie this condition. The goal of this study is to use a newly developed genetically manipulated experimental animal model to study the function of single heart cells. In this model one of the glucose transporters has been deleted. Our goal is to compare heart function in this genetic model with heart function in diabetes. Cells are isolated from hearts using enzyme treatments and investigated microscopically to determine if there are subcellular structural alterations. Functional studies are performed on individual viable cells using a combination of electrical recording techniques and fluorescence imaging methods. The experimental aim is to assess whether there is disruption of sodium, calcium or pH regulation associated with cardiac enlargement associated with metabolic abnormalities. This research will assist in identifying appropriate therapeutic strategies for intervention in the treatment or prevention of conditions associated with cardiac enlargement.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.