Role Of Sphingosine Kinase-1 In Beta Cell Survival And Function.
Funder
National Health and Medical Research Council
Funding Amount
$85,716.00
Summary
Both type 1 and type 2 diabetes remain major health problems in Australia. Although the pancreatic beta-cell death and dysfunction involved in the etiology has been addressed, the mechanisms are still not fully understood. Thus, we seek to establish the role of sphingosine kinase, a strong protector against cell death, in the regulation of beta cell survival and insulin secretion and try to create new therapeutic strategy for the management of diabetes.
Characterising The Beneficial Effects Of Estrogen On The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$594,722.00
Summary
Prostate cancer is hormonally regulated and currently managed by androgen ablation. This application seeks to study the potential benefits of estrogen action for the treatment of prostate disease, including PCa. We will show estrogen hormone action causes prostatic cell death, targeting the stem-progenitor cells so the treated prostatic tissue does not regenerate. This project will provide pre-clinical proof of the efficacy of estrogenic compounds as a potential therapy for prostate disease.
Cellular Responses To Thrombin In Skeletal Pathology
Funder
National Health and Medical Research Council
Funding Amount
$120,775.00
Summary
Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects them from premature death. Thrombin also stimulates t ....Many diseases of bones, such as osteoporosis and delayed fracture repair, result from the abnormal function of bone cells. Factors regulating bone cell function are, therefore, important in maintaining a healthy skeleton, as well as in the skeleton's response to disease. The enzyme thrombin is involved in blood coagulation but also causes bone cells to alter their behaviour. Thrombin stimulates proliferation of bone-forming cells and protects them from premature death. Thrombin also stimulates the breakdown of bone. We will investigate how thrombin's effects on bone cell behaviour influence the course of bone healing. We will also determine how thrombin stimulates bone breakdown and increases survival of bone-forming cells. This study will contribute to the understanding of how bone cells function in health and disease.Read moreRead less
Determinants Of Insulin-like Growth Factor (IGF) Binding And Biological Actions Of IGF Binding Protein-6
Funder
National Health and Medical Research Council
Funding Amount
$399,750.00
Summary
Proteins are complex structures usually consisting of a number of distinct regions. Each of these regions may serve different roles. Insulin-like growth factors (IGFs) are important proteins involved in regulating the growth and other properties of cells. The actions of IGFs are in turn regulated by a family of binding proteins (IGFBPs). The aim of this project is to determine the range of actions of one of these IGFBPs and which parts of this IGFBP are involved in these actions. This may lead t ....Proteins are complex structures usually consisting of a number of distinct regions. Each of these regions may serve different roles. Insulin-like growth factors (IGFs) are important proteins involved in regulating the growth and other properties of cells. The actions of IGFs are in turn regulated by a family of binding proteins (IGFBPs). The aim of this project is to determine the range of actions of one of these IGFBPs and which parts of this IGFBP are involved in these actions. This may lead to new treatments for diseases in which cell growth is disturbed e.g. cancer and diabetes.Read moreRead less
IGF BINDING PROTEIN-2 A MODULATOR OF IGF ACTION IN DEVELOPING AND NEOPLASTIC NEURONAL CELLS.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged ....In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged brain, and in tumours, plays a key role on the surface of neurons in regulating IGF availability. We have shown that IGFBP-2 associates with a specialised protein on the nerve cells, where it is further processed to smaller fragments. We believe that these processes are reactivated following brain injury or in cancer states where IGFBP-2 is highly abundant. We propose to determine how IGFBP-2 influences IGF action on the nerve cell surface, and to further ascertain the function of each step in this process. We will achieve this by examining the effects of the mutated version of IGFBP-2, designed to either prevent its binding to the cell surface or its processing to smaller fragments. We will use various human and mouse nerve cell for these studies, which will not only provide greater understanding of the regulation of IGF availability to developing brain cell, but also point to how these processes may be involved in enhancement of recovery from injury or stroke, or possibly in acceleration of tumour growth. The finding of this study will offer the potential for new and exciting treatment designed to alter the function of the IGF system, to either make it more active in response to brain injury or stroke, or less active in brain tumours.Read moreRead less
Mechanisms Of Hypoglycaemic Damage In Developing Brain- A Protective Role For The Insulin-like Growth Factor System
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children ....The developing brain in the newborn infant or young child is vulnerable to many damaging influences. It is highly dependent on its essential fuel, glucose. Hypoglycemia, or lack of glucose availability, is therefore among the most damaging insults to the young brain, potentially leading to learning difficulties, developmental delay, cerebral palsy or epilepsy. Babies born premature or very small are at risk, as are those exposed to excessive insulin, such as infants of diabetic mothers. Children with diabetes are also at risk, when their therapy with insulin may at times be excessive, leading to hypoglycaemia and impaired glucose availability for the brain. This proposal is examining at the cellular level the mechanisms involved in loss of brain cells in the face of glucose starvation in these various conditions. We are using several in vitro models where we can grow segments of developing mouse brain or human nerve cells in a dish, compared to studies with mice subjected to low blood glucose (hypoglycemia). After establishing that our laboratory models are representative of the whole animal, we will explore the cellular mechanisms involved in neuronal death following hypoglycaemia, particularly the interaction between the insulin-like growth factor (IGF) and other cell survival genes. We will also examine the possibility that treatment with IGF will reduce the loss of nerves in the brain after an episode of hypoglycemia. This may offer new and effective early treatment for this damaging brain injury in both newborn babies and children with insulin-dependent diabetes.Read moreRead less