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
Adiponectin - Multimerization, Secretion And Action
Funder
National Health and Medical Research Council
Funding Amount
$478,844.00
Summary
Adiponectin is a hormone produced by fat tissue. It functions to control blood glucose levels and acts to prevent damage to blood vessels associated with heart disease and stroke. Adiponectin levels in the blood are low in subjects with obesity, diabetes and heart disease, and in animals with these conditions, additional adiponectin is of benefit. It has recently been recognised that adiponectin is produced in different forms - a low weight form made up of a small number of adiponectin molecules ....Adiponectin is a hormone produced by fat tissue. It functions to control blood glucose levels and acts to prevent damage to blood vessels associated with heart disease and stroke. Adiponectin levels in the blood are low in subjects with obesity, diabetes and heart disease, and in animals with these conditions, additional adiponectin is of benefit. It has recently been recognised that adiponectin is produced in different forms - a low weight form made up of a small number of adiponectin molecules and a higher weight form (HMW adiponectin) made up of large numbers of adiponectin molecules complexed together. We and others have shown that the HMW adiponectin is particularly beneficial. This projects aims to understand the processes regulating the production of differing types of adiponectin by fat cells. It will also examine how the different types of adiponectin have their effects in different tissues such as liver and muscle. The information gained will increase our understanding of how illnesses such as diabetes are associated with obesity. It may also lead to the development of treatments aimed at increasing adiponectin levels - particulalry HMW adiponectin - which may be of benefit in patients with diabetes and cardiovascular disease.Read moreRead less
Explaining The Dark Matter Of Genome-wide Association Studies For Complex Disease
Funder
National Health and Medical Research Council
Funding Amount
$453,098.00
Summary
Common diseases, such as psychiatric disorders and cardiovascular disease, are caused by the interplay of genetic and envirionmental factors. In the last 4 years, very large studies have been conducted to associate genetic factors with risk of disease, but these studies have not accounted for known familial risk. We aim to use data on very distant relatives to explain why. Understanding the genetic basis of common disease is crucial to guide future experiments and for developing new treatments.
Genetics Of DNA Methylation And Its Role In Disease Susecptibility
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
DNA methylation is a chemical modification to DNA that sits on the interface of an individual's genetics and environment, which is critical for regulating many cellular processes. There is increasing evidence for a major role of variation in DNA methylation in development of disease and it provides a potential therapeutic target. This research will fill fundamental gaps in our knowledge of the genetic and environmental control of differences in levels of DNA methylation in the population.
A Genome-wide Association Study In 2000 Glaucoma Cases With Matched Controls Using Equimoloar DNA Pools
Funder
National Health and Medical Research Council
Funding Amount
$610,267.00
Summary
Glaucoma is a common cause of loss of vision worldwide but we are unable to predict which people are at high risk of blindness. We aim to discover the genetic risk factors for glaucoma. We will use cutting edge genetic technology to assess the whole genome in thousands of patients with glaucoma. We hope to identify important new glaucoma genes, which could lead to the development of diagnostic tests and treatments which will provide the most cost-efficient ways to prevent glaucoma blindness.