microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried m ....microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried method, and to explore bioinformatics-based methods of identification. We will also study the expression of miRNAs in mouse embryos at successive stages, and develop a microarray assay for miRNA expression.Read moreRead less
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less
Large scale knowledge and image based biomedical modelling and derivation of PET-CT disease maps and treatment response. The smart use of information to improve, promote and maintain good healthcare is a critical mission for our country. Cancer is a serious problem in Australian society and 1 in 4 individuals will be affected by it in their lifetime. Our research is focussed on two types of cancer - lung cancer and the lymphomas - and it will use IT in a novel way to extract important informatio ....Large scale knowledge and image based biomedical modelling and derivation of PET-CT disease maps and treatment response. The smart use of information to improve, promote and maintain good healthcare is a critical mission for our country. Cancer is a serious problem in Australian society and 1 in 4 individuals will be affected by it in their lifetime. Our research is focussed on two types of cancer - lung cancer and the lymphomas - and it will use IT in a novel way to extract important information from a very large biomedical data repository. We hope that it will improve personalised diagnosis and treatment in these cancers and provide new information on how some cancers spread and resist our usual treatments. We think our techniques will contribute to other research areas such as astronomy, agriculture, water/energy resources, and security.Read moreRead less
Information Technology Aided Diagnosis of Dementia with PET-CT Imaging. Dementia is a significant health problem and approximately 162,000 Australians currently suffer from this disease, with costs estimated at $6 billion annually in Australia and a profound effect on the lives of carers and family members. With the ageing of the Australian population, the patient number is expected to rise to 500,000 by 2040.This research will apply innovative IT approaches to develop computer assisted diagnosi ....Information Technology Aided Diagnosis of Dementia with PET-CT Imaging. Dementia is a significant health problem and approximately 162,000 Australians currently suffer from this disease, with costs estimated at $6 billion annually in Australia and a profound effect on the lives of carers and family members. With the ageing of the Australian population, the patient number is expected to rise to 500,000 by 2040.This research will apply innovative IT approaches to develop computer assisted diagnosis of early dementia, when treatment is possible, from combined functional and anatomical imaging modalities (PET-CT). This will not only add considerable value to Australia's medical imaging infrastructure and smart use of information, but will ultimately also deliver substantial benefits to our nation and community.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise ....Identification and characterisation of caspase inhibitors. Organisms use a tightly controlled process of cell death (termed apoptosis) to remove dangerous and unwanted cells. Dysregulation of this process can contribute to diseases such as cancer and autoimmune disease. Caspases are protease effectors of apoptosis. Regulation of their activity is vital for effective control of cell survival and death. Using a functional screening system invented by the 1st CI, we aim to isolate and characterise novel inhibitors of caspases. Such inhibitors may in time be used as targets for development of therapeutic or diagnostic reagents aimed at manipulating the apoptotic process to diagnose, prevent or treat disease.Read moreRead less
How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biol ....How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biology, and will increase our understanding of diseases that arise due to aberrant tissue growth, such as cancer. Our research findings will thus be of substantial national benefit, given that cancer is now the biggest cause of death in Australia, and that more than 88,000 Australians are diagnosed with cancer each year. Read moreRead less
The development and evolution of the pelvic girdle in basal gnathostomes. Comparing the development of muscles, cartilage and bone in representatives of all three major groups of fish will provide information as to how structures evolved but also how the adult morphology is distributed in phylogeny. Because so little is known about the genetic mechanisms underlying the formation of the pelvic girdle in fish, it is important to start studying a model animal such as the zebrafish. The pathways unc ....The development and evolution of the pelvic girdle in basal gnathostomes. Comparing the development of muscles, cartilage and bone in representatives of all three major groups of fish will provide information as to how structures evolved but also how the adult morphology is distributed in phylogeny. Because so little is known about the genetic mechanisms underlying the formation of the pelvic girdle in fish, it is important to start studying a model animal such as the zebrafish. The pathways uncovered have the potential to describe mechanisms common to all jawed vertebrates, not only common to fish. Understanding the mechanisms that generate major morphological transition in the vertebrate lineage necessarily informs us about our own evolutionRead moreRead less
Specification and evolution of vertebrate appendicular muscle. Previously we have determined that two different developmental mechanisms are utilised to make the muscles present within the fins and limbs of distinct vertebrate species. This proposal is concerned with determining the morphogenetic, evolutionary and molecular basis for these two different developmental modes. To do this we will to extend our observations more widely to examine muscle formation in both the paired fins in a phyloge ....Specification and evolution of vertebrate appendicular muscle. Previously we have determined that two different developmental mechanisms are utilised to make the muscles present within the fins and limbs of distinct vertebrate species. This proposal is concerned with determining the morphogenetic, evolutionary and molecular basis for these two different developmental modes. To do this we will to extend our observations more widely to examine muscle formation in both the paired fins in a phylogenetically diverse context. We further hope to determine the underlying genetic basis for these different morphologies by developing techniques to examine their formation in a number of embryonic contexts.Read moreRead less