Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, ....Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, and how this will change the state of the cell. We propose here to use the new technique of gene arrays to uncover the programs, or groups of genes, which GH regulates to change important cellular processes. When used in conjunction with cells expressing GH receptor mutants which are unable to signal to defined pathways, we will be able to know which functional families genes are regulated, and how they are regulated. This information will enable us to know how GH regulates cell growth and metabolism, and therfore to understand what goes wrong when GH or its mediator, IGF-1 , are abnormal. We can also use this information to validate small molecules designed to mimic GH through activating its receptor, to be certain that they are acting in the same way as GH.Read moreRead less
This study combines sophisticated molecular techniques with state-of-the-art biochemical and physiological analyses to determine how gut hormones regulate satiety. By utilising unique conditional and germline KO mice , this research will make highly original and internationally competitive contributions to the understanding of the regulation of satiety and energy expenditure. Knowledge as to the causes of lack of satiety will be of great benefit in the search for novel treatments for obesity.
High Resolution Genome-wide Genomic Analysis Of DCIS To Identify Genes Involved In Disease Initiation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$543,370.00
Summary
DCIS is the most common type of noninvasive breast cancer and in some women may progress to malignant disease but little in know about how it develops. We will bring to bear our experience with cutting edge technology and access to extensive clinical resources to the analysis of a large series of pure DCIS with the aim of identifying previously unknown cancer causing genes. This data will lead to the identification of novel breast cancer genes that will assist clinical management.
Molecular Profiling Of Sarcomas To Enable Clinical Prediction And Elucidate Molecular Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will ....Sarcomas are uncommon cancers which affect the young, with a 50% mortality. Treatment involves an expert multidisciplinary approach, and even when effective often entails long-term loss of quality of life. Most sarcomas are treated with a combination of radiotherapy and surgery, which improves survival significantly compared to surgery alone. Radiotherapy does not help all patients, has side-effects and is expensive and time consuming. It would be useful to be able to identify patients who will not benefit from radiotherapy, to minimise unnecessary harm from treatment and offer alternate more effective therapies. Unfortunately, we cannot yet distinguish which tumours will respond and which will not. Moreover, the uderlying causes of sarcoma are poorly understood. This project has two aims: first to make our current therapies more effective by targeting those who will not benefit from standard treatment; and second to better understand the causes of sarcoma, in order to develop better treatment. Microarrays enable the simultaneous study of thousands of genes, which when combined form a unique portrait of each tumour. Our unit, one of the largest sarcoma sevices in Australia, has access to large numbers of tumour samples, with excellent basic science support. It is now possible to ask what the molecular 'portrait' is of sarcomas which are responsive to radiotherapy, using tiny amounts of tumour material which can be obtained before treatment starts. We also hope to identify the molecular basis of sarcomas by finding the key genes whose inactivation is central to the development of this form of cancer. Such genes can then form the basis of targeted therapy. This approach will lay a solid foundation for future research into sarcomas, and has the potential to reduce unnecessary cost and suffering patients experience from treatments which are unlikely to be effective.Read moreRead less