Focimatrix Regulation Of Sex Steroid Hormones In The Ovary
Funder
National Health and Medical Research Council
Funding Amount
$291,309.00
Summary
Sex steroid hormones (e.g. oestrogen and testosterone), are important to male and female health. In the ovarian follicle I identified a novel form of extracellular matrix (focimatrix) which develops in the ovary before the synthetic enzymes needed for sex steroids are present. Using evidence from other tissues, I developed ideas on how this matrix regulates the enzymes for hormone synthesis. I will examine a mechanism by which focimatrix could directly affect steroid hormone production.
Interactions Between Advanced Glycation And Oxidative Stress In Diabetic Renal And Cardiac Complications
Funder
National Health and Medical Research Council
Funding Amount
$431,700.00
Summary
Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's a ....Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.Read moreRead less
Pathways Involved In The Insulin-like Growth Factor (IGF)-independent Actions Of IGF Binding Protein-6
Funder
National Health and Medical Research Council
Funding Amount
$550,725.00
Summary
Insulin-like growth factors (IGFs) are important proteins that regulate growth. When not regulated properly, diseases such as cancer can occur. A family of IGF binding proteins regulates IGFs. IGFBPs may inhibit IGFs and we have shown that one of them, IGFBP-6, decreases growth of some experimental cancers. As well as regulating IGFs, some IGFBPs alter cell behaviour independently of IGFs, and we found that IGFBP-6 stimulates cell movement in this way. We will now determine how this happens.
The Role Of Ezrin-radixin-moesin Proteins, Novel Binding Proteins For Advanced Glycation Endproducts, In Kidney Cells
Funder
National Health and Medical Research Council
Funding Amount
$493,220.00
Summary
High glucose levels in diabetes react with proteins to form AGEs and it is thought that this reaction may lead to kidney damage, which is one of the complications of diabetes. However, how this damage occurs is not completely understood. Cells need to maintain their shape and position for an organ to stay healthy. We have shown that AGEs affect kidney cells by interacting with and disturbing the function of proteins that maintain cell shape. We now want to study how this occurs.
Insulin-like Growth Factor (IGF)-II Binding Specificity Of IGF Binding Protein-6: Structural And Functional Studies.
Funder
National Health and Medical Research Council
Funding Amount
$265,630.00
Summary
Insulin-like growth factor II (IGF-II) is a protein which is involved in normal growth. However, in some circumstances it may also stimulate cancer growth. IGF binding protein-6 (IGFBP-6) binds to IGF-II and stops its activity. One of the major challenges of modern biology is understanding why some proteins bind to other proteins. Proteins fold in various ways and have specific three-dimensional structures. Two proteins which bind strongly to each other have structures which fit each other like ....Insulin-like growth factor II (IGF-II) is a protein which is involved in normal growth. However, in some circumstances it may also stimulate cancer growth. IGF binding protein-6 (IGFBP-6) binds to IGF-II and stops its activity. One of the major challenges of modern biology is understanding why some proteins bind to other proteins. Proteins fold in various ways and have specific three-dimensional structures. Two proteins which bind strongly to each other have structures which fit each other like a 'lock and key'. The aim of this project is to understand how IGFBP-6 binds to IGF-II by looking at its three-dimensional structure. Using this information, it may be possible to develop new treatments which can inhibit IGF-II activity and therefore may be useful in the treatment of some cancers.Read moreRead less
Evaluation Of Functional Protein Molecules In Treating Obesity
Funder
National Health and Medical Research Council
Funding Amount
$349,407.00
Summary
This project aims to reduce excessive food consumption by controlling the satisfaction that people get from eating. This will be achieved through varying protein supplements (whey, leucine and beta-conglycinin) and their combinations. The idea is that people will feel satisfied despite eating less, leading to weight loss and the correction of related metabolic disorders.
Kallikrein Proteases Have Key Functional Roles In Peritoneal Invasion And Chemoresistance In Epithelial Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$815,541.00
Summary
Only 30% of ovarian cancer patients with advanced disease survive for 5 years. This is because the cancer quickly spreads into the abdominal cavity and often becomes resistant to chemotherapy. We aim to use a new 3D culture system, mouse models and novel inhibitors to study the roles of 4 kallikrein enzymes in these events. The outcomes from this study will lead to a better understanding of the role of kallikreins in ovarian cancer and may lead to new treatment approaches.
Of Mice And Men: Assessing Dietary Proteins Role On Appetite Regulation, Obesity And Cardiovascular Risk
Funder
National Health and Medical Research Council
Funding Amount
$86,521.00
Summary
While the challenge of understanding and managing the global obesity epidemic is well recognised, the role that nutrition plays is more complex than at first glance. Dietary protein may be of central importance in managing weight and small changes in protein consumption may lead to large changes in energy intake and weight. We propose to look at the effects of dietary protein on appetite, its hormonal regulation, and on the risk of developing metabolic diseases such as diabetes.