Pushing AR Toward Better Outcomes In Breast And Prostate Cancers
Funder
National Health and Medical Research Council
Funding Amount
$998,754.00
Summary
Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives ....Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives.Read moreRead less
The Clinical Significance Of Sex Hormone Crosstalk In Estrogen Receptor Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,009,006.00
Summary
Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth. We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This study will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.
Characterisation Of Erusiolin - A New Peptide Hormone
Funder
National Health and Medical Research Council
Funding Amount
$547,202.00
Summary
Obesity and type II diabetes are epidemic diseases in Australia. Gut-derived hormones are key mediators in these diseases, due to their role in regulating appetite and blood glucose levels. Therapeutic modulation of these hormones also provides significant benefits for patients. In this proposal, we will determine the metabolic functions, such as appetite control, for a previously uncharacterised hormone, which is an unexplored therapeutic target for obesity and diabetes.
Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essenti ....Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essential target genes that drive lymphatic development. The project expects to generate fundamental knowledge in vascular signalling, transcription and the control of vascular network growth and expansion. Outcomes may provide significant benefits in new approaches in stem cell biology, tissue engineering and regenerative biology. Read moreRead less
Progesterone Receptor-mediated Coordination Of Oocyte-oviduct Communication During Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$86,128.00
Summary
Infertility affects 1 in 6 couples, often due to failed release of an egg from the ovary. The hormone progesterone is essential for this process. Our goal is to determine how progesterone signals the egg to ensure its correct release into the oviduct where fertilization may occur. To identify these signals, experiments will analyse ovary cells and eggs of mice, including mice that do not respond to progesterone. The results will provide much needed information about female reproductive health.
Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precurs ....Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precursors differentiate either along the male or the female pathway. Thus, this project aims to analyse in detail at which stage NEDD4 action is required and what are the crucial target proteins. This project could provide a deeper understanding of how post-translational modifications influence cell fate decisions during embryogenesis.Read moreRead less
Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromoso ....Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromosomes at mitosis, meiosis and in sperm. I will use immunohistochemistry to clarify chromosome pairing and recombination at meiosis. This will answer some important general questions about chromosome behaviour and sex chromosome evolution.
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Genetic control of floral architecture. Different flowers have different designs, and so the design must ultimately be controlled by genes. We have identified a gene that keeps sepals separate, and promotes the initiation of petals. We think it does this by a novel growth suppression mechanism, and will now deduce its molecular and cellular basis. This will help maintain Australia's strength in fundamental plant biology. Also, by understanding how sepals and petals arise in a model laboratory sp ....Genetic control of floral architecture. Different flowers have different designs, and so the design must ultimately be controlled by genes. We have identified a gene that keeps sepals separate, and promotes the initiation of petals. We think it does this by a novel growth suppression mechanism, and will now deduce its molecular and cellular basis. This will help maintain Australia's strength in fundamental plant biology. Also, by understanding how sepals and petals arise in a model laboratory species, we can generalise for many species, including economic plants. Thus it may be possible to make designer crops through targeted genetic changes to their floral structure.Read moreRead less
Control of plant organ development by the PETAL LOSS gene of Arabidopsis. We have discovered a new gene in the model laboratory plant Arabidopsis thaliana that is involved in sepal and petal development. It encodes a transcription factor that apparently acts by repressing growth in the inter-sepal zone of flowers where petals arise. We now aim to determine how this growth suppression occurs, and whether it extends to leaves where the gene is also expressed. Control of the initiation and sculptur ....Control of plant organ development by the PETAL LOSS gene of Arabidopsis. We have discovered a new gene in the model laboratory plant Arabidopsis thaliana that is involved in sepal and petal development. It encodes a transcription factor that apparently acts by repressing growth in the inter-sepal zone of flowers where petals arise. We now aim to determine how this growth suppression occurs, and whether it extends to leaves where the gene is also expressed. Control of the initiation and sculpturing of plant organs by site-specific inhibition of growth is a newly discovered mechanism that may be useful in manipulating plant architecture.Read moreRead less