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.
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
The Identification Of Novel Genes Involved In The Initiation And Development Of Thyroid Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid c ....Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid cancer. However mutations, mistakes in the genetic code, of these genes account for only a small percentage of thyroid tumours and none of these genes have been shown to be useful as clear prognostic markers for tumour progression or aggressiveness. The merging of the 2 fields of cytogenetics (the study of chromosomes) and molecular genetics (the study of genes at the DNA and RNA level) has strengthened our ability to understand the process of tumour development. We are proposing use of a technique called Comparative Genomic Hybridisation to aid in the identification of new genes associated with tumour development in both benign and malignant thyroid disease. This technique has already been used to aid in the location of genes with a role in ovarian and brain cancer and in some familial syndromes characterised by breast and gastrointestinal malignancies. This method involves the detection of regions of chromosomal amplifications or deletions in tumour DNA that is fluorescently labelled (green), mixed with normal human DNA also fluorescently labelled (red). If the tumour contains regions of amplification (likely housing an oncogene), analyses show increased green fluorescence and if deletions are present (likely housing a tumour suppressor gene), analyses show increased red fluorescence. Chromosomal regions identified by this method will be further analysed to identify the precise genes they contain and establish a role for these genes in the development of thyroid tumours.Read moreRead less