Adrenocortical cancers have a poor prognosis. It is essential that patients with adrenocortical cancers be diagnosed early and accurately to enable the initiation of appropriate treatment. Current methods do not reliably differentiate benign adrenal tumours from adrenocortical cancers. The aim of my project is to identify molecular markers which can accurately distinguish benign adrenal tumours from adrenocortical cancers, allowing accurate diagnosis and institution of optimal therapy.
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.
Role Of Liver Receptor Homologue-1 (LRH-1) In Male Germ Cells
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
Historically the steroid sex hormones - oestrogens and androgens - have been regarded as female- and male- specific sex hormones, respectively. Oestrogens are produced by the ovary and regulate female-specific processes such as ovulation and development of female sexual characteristics, whereas androgens are produced by the testis and regulate male-specific functions. However it is now clear that the distinction between oestrogen and androgen is not a sharp one. For example, we now know that oes ....Historically the steroid sex hormones - oestrogens and androgens - have been regarded as female- and male- specific sex hormones, respectively. Oestrogens are produced by the ovary and regulate female-specific processes such as ovulation and development of female sexual characteristics, whereas androgens are produced by the testis and regulate male-specific functions. However it is now clear that the distinction between oestrogen and androgen is not a sharp one. For example, we now know that oestrogens are produced within the testis and play a very important role in male fertility. Human males patients who are unable to synthesise oestrogens are infertile. Similarly, mice that cannot produce oestrogens are also infertile, due to a defect in sperm production. Oestrogens are therefore critical for normal male fertility, and reduced oestrogen production within the testis may be a significant cause of infertility which would be easily treatable in the clinic. The protein LRH-1 regulates oestrogen production in other tissues. This proposal aims to identify the role of LRH-1 in testicular oestrogen production by identifiying the genes regulated by LRH-1 and the proteins that interact with it in the testis. We also aim to study the structure of these proteins in infertile men. These studies will define new genes associated with male infertility and may lead to the development of more effective treatments for this common condition.Read moreRead less
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.
An Examination Of The Contribution Of Visceral Adiposity To Insulin Resistance In Humans.
Funder
National Health and Medical Research Council
Funding Amount
$335,800.00
Summary
The worldwide epidemic of Type 2 diabetes is related to major nutritional and activity changes interacting with a genetic predisposition. The two key defects in Type 2 diabetes are a reduced response to insulin (insulin resistance) and relative failure of insulin production. Insulin resistance is the earliest defect and is closely associated with cardiovascular risk. Obesity generates insulin resistance, but intraabdominal (visceral) fat has particular importance. Visceral fat cells are differen ....The worldwide epidemic of Type 2 diabetes is related to major nutritional and activity changes interacting with a genetic predisposition. The two key defects in Type 2 diabetes are a reduced response to insulin (insulin resistance) and relative failure of insulin production. Insulin resistance is the earliest defect and is closely associated with cardiovascular risk. Obesity generates insulin resistance, but intraabdominal (visceral) fat has particular importance. Visceral fat cells are different to other fat cells; they are very metabolically active and 'spill out' fatty acids indiscriminately contributing to insulin resistance in liver and muscle; they also produce hormones which may modify the action of insulin. We will study people undergoing abdominal surgery. Participants will be (1) normal weight and sensitive to insulin, (2) abdominally overweight and insulin resistant, (3) insulin resistant with Type 2 diabetes. We will document abdominal fat, circulating lipid and hormone levels and insulin action. At surgery fat biopsies will be obtained from (a) inside the abdominal cavity, (b) the fat layer under the abdominal skin and (c) fat in the buttock. The activity of a large number of genes in the fat tissue will be assessed in 8 subjects using DNA array (4 each from Groups 1 and 2). Then a small number of genes will be selected on the basis of different activity in visceral fat from buttock fat, and between insulin sensitive and insulin resistant people. The activity of these genes will be determined in all subjects in the 3 groups. We anticipate identifying a few (perhaps 3) genes whose activity is closely associated with insulin resistance and will examine their capability to block insulin action in a series of animal and cellular studies. These studies should identify specific mechanisms by which visceral fat creates insulin resistance. This would be an important step towards prevention and improved medication for Type 2 diabetes.Read moreRead less