The Role Of Central And Peripheral Synaptic Activity In The Developmental Death Of Motoneurons.
Funder
National Health and Medical Research Council
Funding Amount
$463,145.00
Summary
Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on ....Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on the neuromotor system as it is a well characterised part of the nervous system. During development, 50% of motoneurons die at a time when they are making contact with skeletal muscle, and when contacts onto motoneurons by other neurons are being established. We believe that the formation of effective synaptic contacts onto motoneurons, as well as connections by motoneurons onto muscle are the key regulators of motoneuron survival. We are in a position to be able to address what regulates motoneuron death; as we have a number of mice which lack key molecules needed for the formation of specialisations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motoneurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motoneurons' fate is determined during developmental motoneuron death. This research could help in developing strategies aimed at improving neuronal connections to improve neuronal viability. Our research will have important implications for our understanding about the basis of adult neuro-degenerative diseases, such as motor neuron disease and Alzheimer's, which are in part characterised by a molecular breakdown in neuronal connections that ultimately result in neuronal death.Read moreRead less
Identification Of Novel Regulatory Factors In Midbrain Development To Improve Cell Therapies For The Treatment Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Cell transplantation is one of the most promising therapeutic strategies for the treatment of Parkinson’s disease. Cells are transplanted directly into the brain of the patient and can compensate for those lost to the disease. In this project we are identifying new genes that regulate the normal development of the transplanted cells in mice. We hope to use this knowledge to improve the reliability and effectiveness of the approach, bringing the therapy closer to the clinic.
Cell death by a specialised process known apoptosis is a way of deleting unwanted and harmful cells from the body. As such, aberrant apoptosis is associated with a wide array of diseases including cancer. For example, abnormal levels of proteins that suppress apoptosis or enhance cell survival can result in cancer and often produce resistance to chemotherapy. To understand and treat cancers that result from aberrant apoptosis we need to know at a molecular level how apoptosis is regulated. Centr ....Cell death by a specialised process known apoptosis is a way of deleting unwanted and harmful cells from the body. As such, aberrant apoptosis is associated with a wide array of diseases including cancer. For example, abnormal levels of proteins that suppress apoptosis or enhance cell survival can result in cancer and often produce resistance to chemotherapy. To understand and treat cancers that result from aberrant apoptosis we need to know at a molecular level how apoptosis is regulated. Central to the apoptosis execution are a group of enzymes called caspases that target many cellular proteins for specific cleavage. In this proposal, we will investigate the function of one of the caspases (called caspase-2), in order to better understand its potential role in the apoptosis of cancer cells. A number of recent reports suggest that caspase-2 levels are reduced in many cancer cells. The human caspase-2 gene localizes to a chromosomal region frequently affected- deleted in leukaemia, and caspase-2 levels have been proposed to be predictors of remission and survival in patients with some types of leukaemia. We will study if loss of caspase-2 in cancer cells makes them resistant to killing by drugs and if mice lacking caspase-2 have an increased potential to develop cancer. Understanding caspase-2 function and its regulation is likely to provide new therapeutic opportunities and potential targets for cancer therapy.Read moreRead less
Dementias affect a large number of Australians each year with the number of patients expected to triple by 2050. As such, there is need to develop a better model of this debilitating disorder to provide improved treatments. Mesenchymal stem cells, are relatively easy to obtain and grow, and are able to produce the key cell types in the brain. We can use these cells to identify the processes that control the production of brain cells, which will likely provide better treatment of this disease.
Manipulation Of Enteric Neural Stem Cells For Cell Therapy To Treat Enteric Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$611,438.00
Summary
Cell therapy offers great promise for the treatment of motility disorders due to defects in the nerve cells in the bowel. Patient-derived cells are likely to be the best source of cells, however, patient-derived cells will require manipulation because they are likely to be defective. We will identify manipulations of stem/progenitor cells that increase their efficacy for cell transplantation.
Understanding how the brain grows and is organised is one of the great challenges of science. This project seeks to identify key regulators of neural progenitors as these are the building blocks from which all brains cells are derived. This knowledge may also identify new avenues through which to manipulate neural progenitor function. This has implications not only for normal brain development but also potential therapies for neural disorders and disease.
Defining Role Of Inflammatory Signals In Enhancing Motoneuron Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$546,688.00
Summary
Spinal cord injury is a devastating event that has a life-long impact on the patient’s life with wide-reaching social and economic effects. In this proposal we examine how inflammatory signals boost neuronal regeneration after injury. Furthermore, we define how new neurons are able to integrate into existing spinal circuitry. Out work provides critical insight and hold keys to unlocking strategies for future restorative therapies in the brain or spinal cord.