Molecular Mechanisms Of Dynamin-mediated Endocytosis In Nerve Terminals
Funder
National Health and Medical Research Council
Funding Amount
$1,033,626.00
Summary
Neurons communicate by neurotransmitter release from synaptic vesicles stored in nerve endings. There is a finite vesicle number, so they are recycled (endocytosis) by the protein dynamin. Our aim is to reveal how new vesicles are produced when the brain is under very high activity, to better understand diseases of the synapse like epilepsy. We propose that two forms of the dynamin gene mediate this process, only under conditions of high neuronal firing, such as occurs during a seizure.
Phosphorylation Of Synaptic Vesicle Glycoprotein 2 (SV2) Regulates Endocytosis Of Synaptotagmin For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Antiepileptic drugs typically target ion transporters or neurotransmitter receptors. Synaptic vesicle glycoprotein 2 (SV2) is a rare example of a synaptic vesicle recycling protein that is the target of an antiepileptic drug. It also binds botulinum and tetanus neurotoxins. We discovered SV2 contains activity-dependent signalling molecules. Charactersation of these molecules and will allow a deeper understanding of the molecular basis for its role in epilepsy and toxin action.
The brain exerts a restraining influence over the heartbeat via the vagus nerves. This is known as cardiac vagal ‘tone’. It is strong when we are healthy but weak when we are sick. It has a positive influence on the health of the heart and perhaps the body generally. Vagal tone comes from the brain but, despite over 150 years’ research, nobody knows exactly where. Using a novel technique, we can track down its origins. This important basic knowledge may lead to ways to improve health.
Non-invasive Retinal Vein Pulsation Pressure Measurement: A New Assessment Of Glaucoma Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$557,666.00
Summary
Glaucoma is the second most common cause of blindness. It is a slowly degenerating disease and the level of treatment required is difficult to predict. At present there is no way of knowing whether the eye is receiving inadequate treatment. We have shown that retinal vein pulsation pressure measurements are an indicator of the likelihood of glaucoma progression. Our proposed studies hope to demonstrate for the first time that it is feasible to determine the appropriate treatment level for indivi ....Glaucoma is the second most common cause of blindness. It is a slowly degenerating disease and the level of treatment required is difficult to predict. At present there is no way of knowing whether the eye is receiving inadequate treatment. We have shown that retinal vein pulsation pressure measurements are an indicator of the likelihood of glaucoma progression. Our proposed studies hope to demonstrate for the first time that it is feasible to determine the appropriate treatment level for individual patients.Read moreRead less
Making Sense Of Novel Ocular Neuroimmune Interactions.
Funder
National Health and Medical Research Council
Funding Amount
$436,178.00
Summary
It is becoming clear that the interaction between corneal nerves and immune cells underpin many inflammatory conditions of the ocular surface. Despite this increased interest, very little is known about the relationship between corneal nerves and immune cells in this outermost layer of the eye. This project will investigate the relationship between corneal nerves and immune cells during health and corneal inflammation to identify therapeutic targets to treat corneal disease.
Boosting Mitochondria- A New Approach For Protecting The Aging Optic Nerve In Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$391,784.00
Summary
Increasing age is a major risk factor for neurodegeneration. We have recently shown that subjecting mice to intermittent periods of fasting improves mitochondrial function in the retina and reverses age-related decline in optic nerve vulnerability to injury. This project now aims to investigate key molecular pathway for restoring mitochondria and from this attempts to find more palatable therapeutic strategies for protecting the optic nerve from injury.
Endometriosis affects up to 10% of reproductive aged women causing a range of debilitating symptoms including pelvic pain and infertility. Our team has discovered that small nerve fibres can be found in the endometrium of women with endometriosis that are not present in women without the condition. We will investigate how these nerve fibres grow and the mechanisms of pain generation. This will potentially allow the development of more targeted and effective treatment modalities.
Mechanisms Underlying The Efficacy Of Bariatric Surgery – Insights From Rat Models Of Sleeve Gastrectomy And The Adjustable Gastric Band
Funder
National Health and Medical Research Council
Funding Amount
$868,472.00
Summary
Bariatric surgery is the only effective treatment for morbid obesity. In order to better understand the mechanistic bases of two such procedures, the adjustable gastric band and sleeve gastrectomy, we have developed rodent models. Here we use these models to better understand the physiology and pathophysiology of these surgeries and extend these findings to inform part of a RCT aimed at identifying the basis for effective joint surgical and medicinal treatments of obesity.
Saving The Optic Nerve : Manipulating The Shp2-Caveolin Axis
Funder
National Health and Medical Research Council
Funding Amount
$546,395.00
Summary
Glaucoma is a leading cause of blindness with many patients experiencing progressive vision loss despite treatment. We propose to use gene therapy techniques to manipulate the signalling pathway of Brain Derived Neurotrophic Factor and its receptor, along with biochemical and functional approaches to understand the mechanisms of glaucoma mediated eye damage and to develop new therapeutic strategies.
Functional Neurogenesis In The Injured Neocortex Of The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$966,048.00
Summary
Research over the past couple of decades has revolutionised our understanding of the capacity of the brain to generate new cells, especially following an injury. However, what does remain controversial is whether this phenomenon occurs in all areas of the brain, especially following a severe traumatic brain injury or stroke. This project will examine whether the outer surface of the brain has the potential to generate new cells following a brain injury and whether they become functional.