MECHANISMS OF TRANSMITTER SECRETION AT SYMPATHETIC NERVE VARICOSITIES
Funder
National Health and Medical Research Council
Funding Amount
$438,707.00
Summary
The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, ....The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, synaptobrevin, SNAP25 and synaptotagmin) together with a calcium channel are complexed with a docked synaptic vesicle containing a quantum of transmitter in a module of secretion appropriately called a secretosome. The leading questions here are to determine if only a single secretosome participates in transmitter release on the arrival of a nerve impulse, whether the number of these secretosomes in a varicosity determines its probability for secretion of a quantum, and fundamentally, how do the proteins within the secretosome cooperate to trigger exocytosis when there is sufficient calcium influx through the secretosome-associated calcium channel following the impulse. The other problem concerns the mechanism of removal of calcium from the varicosity once it has entered through the channels, This calcium can have considerable affects on the extent to which secretosomes participate in secretion with subsequent impulses. Furthermore, this influx of calcium can be modulated for subsequent impulses by transmitter released by the first impulse. The present research will solve these problems, providing a molecular description of secretion from single sympathetic varicosities.Read moreRead less
Novel Methods For Promoting Organ Development And Growth
Funder
National Health and Medical Research Council
Funding Amount
$390,203.00
Summary
A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of Colony Stimulating Factor (CSF-1). We have evidence that CSF-1 therapy can promote kidneys and lungs to continue development and maturation after birth. This exciting new finding allows for the application of CSF-1 therapy for both the treatment of premature babies and unborn babies with kidney defects.
Hormonal Resuscitation And P38 MAP Kinase Inhibition To Enhance Quality Of Cadaveric Donor Organs For Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this proj ....The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this project, we will use a pig model of brain death that we have extablished in our laboratory to examine the effects of hormone replacement on the function of organs that are used for transplantation. We will also test a novel drug aimed at protecting donor organs during the period between removal of the organ and transplantation. If successful, these treatments have the potential to markedly increase the numbers of organ transplants and to improve the outcomes for recipients of these transplants. In the Australian and New Zealand setting, a 25% increase in the number of donor organs would results in approximately 220 more people per year receiving these life-saving operations.Read moreRead less
Globally, zebrafish are making a very significant impact on biomedical research. Zebrafish have a number of attributes that make them ideal models for the study of development and disease, including: - adults are relatively small, so housing is cheap - eggs are transparent, so early developmental processes can be visualized easily - development is rapid - organs are made in 1-7 days - zebrafish are vertebrates and thus have a gene complement very similar to humans - large numbers of eggs are pro ....Globally, zebrafish are making a very significant impact on biomedical research. Zebrafish have a number of attributes that make them ideal models for the study of development and disease, including: - adults are relatively small, so housing is cheap - eggs are transparent, so early developmental processes can be visualized easily - development is rapid - organs are made in 1-7 days - zebrafish are vertebrates and thus have a gene complement very similar to humans - large numbers of eggs are produced each week from a single mother, aiding experimentation - ENU mutagenesis screens have generated thousands of useful mutants, including an increasing number that accurately model human genetic diseases - high-resolution imaging of RNA and protein expression in whole embryos is easy - drugs and chemicals can be easily tested for activities in zebrafish by adding them to the water Becuase of these attributes, zebrafish are becoming the model organism of choice for the study to human development and disease - indeed, the zebrafish field is growing at three times the rate of the mouse field. The international biomedical community has invested very heavily in infrastructure to aid the zebrafish community in realising the potential of this model. In Australia we have very strong basic research teams whom have embraced zebrafish mdoels. However, we lag behind other parts of the world in that, as yet, we have not had much specific funding allocated to animal model infrastructure. This Enabling Grant will build unique infrastructure by bringing together the zebrafish community with two areas in which Australia is very strong - genomics and biodiversity. This will result in a greatly enhanced ability to determine how genes work, and a pipeline for screening Australia's rich source of natural products and chemical libraries for activites against common human diseases such as cancer, dementia, and muscle diseases using zebrafish models.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130101222
Funder
Australian Research Council
Funding Amount
$371,392.00
Summary
The development of novel magnetic resonance imaging methods to investigate brain structure and function. Magnetic resonance imaging (MRI) is a non-invasive method that has revolutionised neuroscience. The goal of this project is to develop state-of-the-art MRI analysis methods that reveal new information about brain structure and function. These novel neuroimaging tools will be instrumental in furthering our understanding of how the brain works.
Advanced magnetic resonance imaging methods for the characterisation of brain structure and function. Magnetic resonance imaging (MRI) is a non-invasive method that has revolutionised the development of neuroscience and neurology. The goal of this project is to develop advanced MRI methods for the study of brain structure and function which will be applied to the investigation of epilepsy and stroke.
Global Data Mapping And Evaluation Of Needs, Capacities And Benchmarks In Organ Donation And Transplantation: Informing Effective Local And International Health Policy To Better Meet The Needs Of Patients
Funder
National Health and Medical Research Council
Funding Amount
$318,575.00
Summary
Global shortages of donor organs limit the provision of reliable and equitable access to solid organ transplantation. As a result, many are excluded from waiting lists, others deteriorate whilst awaiting transplantation, and some seek to purchase the needed organ. Countries have a responsibility to provide transplantation services sufficient to meet population need. This project evaluates international data for key interventions that may impact on waitlisting, donation and transplant practices.