Determining The Impacts Of Epigenetic Modifying Drugs On Germline Programming And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$863,918.00
Summary
New drugs have been developed that inhibit specific enzymes that regulate epigenetic pathways in cells. These pathways significantly affect growth and development in offspring and may represent a risk to future children of patients taking the drug. This project will determine these risks and provide data for developing clinical guidelines for safe use of the drugs.
Hedgehog Signalling In Limb And Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,544.00
Summary
Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in b ....Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in both limb and face development. Based on the organs in which our genes of interest are active, we believe that they will also play key roles in embryonic development of the limbs, face and other organs. We now plan to investigate the regulation of a subset of these genes based on analysis in mouse models of limb and face development. In addition, we have chosen to further analyse the function of a completely novel gene we have identified which our preliminary studies suggest may play a role in the normal development of the lip and palate. These studies have the potential to shed light on the processes governing how organs develop, as well as on the molecular basis of common birth defects such as polydactyly (extra fingers and toes) and cleft palate.Read moreRead less
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
A new generation of multi-modality biomedical image visualisations. This research will overcome the urgent and significant burden in the routine clinical visualisation of multiple-modality biomedical image data, which are complex and exquisitely detailed from the new generation of high-resolution medical imaging scanners. Together with our industry partner RPA Hospital, we will produce 3D visualisation methodologies that will simplify and revolutionise the way biomedical data are visualised, ana ....A new generation of multi-modality biomedical image visualisations. This research will overcome the urgent and significant burden in the routine clinical visualisation of multiple-modality biomedical image data, which are complex and exquisitely detailed from the new generation of high-resolution medical imaging scanners. Together with our industry partner RPA Hospital, we will produce 3D visualisation methodologies that will simplify and revolutionise the way biomedical data are visualised, analysed and interpreted by imaging specialists and disseminated to doctors and patients. Given the pivotal role that imaging plays in modern healthcare, this will improve diagnosis and assessment, and enhance Australia's leading position in the development of frontier technologies.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
Integrated multi-level interpretation and its applications for intelligent multimodality biomedical image navigation, retrieval and tracking. The 64- and 128-slice positron emission tomography – computed tomography (PET-CT) devices at the Royal Prince Alfred Hospital were the first in the country. These scanners, with the medical cyclotron and radiochemistry facilities, represent an investment of over A$13 million. This project will address pressing issues in optimising the utilisation of the in ....Integrated multi-level interpretation and its applications for intelligent multimodality biomedical image navigation, retrieval and tracking. The 64- and 128-slice positron emission tomography – computed tomography (PET-CT) devices at the Royal Prince Alfred Hospital were the first in the country. These scanners, with the medical cyclotron and radiochemistry facilities, represent an investment of over A$13 million. This project will address pressing issues in optimising the utilisation of the information and systems to provide better service to patients and referring clinicians. This research will add considerable value to Australia's medical imaging infrastructure and healthcare delivery; and advance scientific research in better understanding of system biology, physiology and pathology. The research outcomes will strengthen Australia’s leading position in biomedical information technology research and Australian medical imaging expertise.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