Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new treatments.
Molecular Regulation Of Metabolism And Body Composition By Ski Via Crosstalk With Nuclear Hormone Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Obesity is a common and burdensome health problem in the community which leads to diabetes and heart disease. A number of factors, including hormones play important roles in determing risk of obesity. This study proposes to investigate whether the Ski gene which is a regulatory factor for many hormones affects metabolism in transgenic mouse models of altered Ski function. The proposed studies may identify Ski as a target for therapy for obesity and improvement in sketal muscle metabolism.
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Examining The Metabolic And Cognitive Deficits Caused By Insulin Resistance In The Ventral Striatum
Funder
National Health and Medical Research Council
Funding Amount
$400,372.00
Summary
Brain insulin resistance is thought to cause metabolic and cognitive deficits, but the underlying neural mechanisms remain elusive. This project addresses this gap in our knowledge by examining how brain insulin resistance disrupts the metabolic regulation of food intake and the cognitive control of actions. The outcomes will provide new insights in disorders characterised by brain insulin resistance such as obesity and dementia.
Initial Interactions Of Herpes Simplex Virus With Innate Immune Cells In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$522,589.00
Summary
Herpes simplex viruses 1 and 2 cause widespread and occasionally serious diseases including genital herpes, neonatal death and encephalitis. Current vaccine candidates are at best partially effective. This grant will examine the way that the virus enters, initially spreads within the skin and interacts with immune cells to help determine which cells should be stimulated by vaccines.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders