Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775778
Funder
Australian Research Council
Funding Amount
$196,000.00
Summary
A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. ....A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. The project falls within the designated national research priority areas of 'promoting and maintaining good health" and the priority goals of "a healthy start to life", "aging well", "aging productively" and "preventative health care."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
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
The transcriptional control of lymphatic vessel development. Lymphatic vessels are a vital, but often overlooked, component of the cardiovascular system. These specialised vessels return tissue fluid to the bloodstream, absorb dietary lipids and transport cells of the immune system throughout the body. Defects in the growth and development of lymphatic vessels result in disorders including lymphedema, obesity, inflammatory diseases and cancer. This project aims to define how transcription factor ....The transcriptional control of lymphatic vessel development. Lymphatic vessels are a vital, but often overlooked, component of the cardiovascular system. These specialised vessels return tissue fluid to the bloodstream, absorb dietary lipids and transport cells of the immune system throughout the body. Defects in the growth and development of lymphatic vessels result in disorders including lymphedema, obesity, inflammatory diseases and cancer. This project aims to define how transcription factors program lymphatic vessel identity and control the development of lymphatic vessel valves. This knowledge will provide new insight into the fundamental mechanisms by which the lymphatic vasculature is constructed during development.Read moreRead less
HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility. This project is to define the biochemistry of a previously uncharacterized protein in male fertility using a unique mouse model and innovative DNA and protein technologies. This project will define a novel, and essential, pathway for male fertility and may ultimately have relevance to the maintenance of health or improving fertility.
Ageing and the muscle stem cell niche. Adult stem cells are critical for repair and maintenance of tissues and ageing tissues show reduced stem cell function. This project will focus on how ageing leads to disruption of communication between muscle stem cells and their niche. The project aims to identify new therapeutic targets for age-related muscle wasting and reduced mobility in the elderly.
Single Minded 2: Cross coupling or specificity within the bHLH/PAS transcription factor family? Understanding the mechanisms of action of SIM2 may lead to novel ideas towards drug development for diseases such as Down syndrome and cancer. The SIM2 protein can interfere with activity of the related Hypoxia Inducible Factor (HIF), a protein important in stress response and recovery from stroke. Understanding the molecular basis of this interference could aid current strategies being used to manipu ....Single Minded 2: Cross coupling or specificity within the bHLH/PAS transcription factor family? Understanding the mechanisms of action of SIM2 may lead to novel ideas towards drug development for diseases such as Down syndrome and cancer. The SIM2 protein can interfere with activity of the related Hypoxia Inducible Factor (HIF), a protein important in stress response and recovery from stroke. Understanding the molecular basis of this interference could aid current strategies being used to manipulate HIF for pharmaceutical benefit.Read moreRead less
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.
Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 fun ....Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 function in the testes including stem versus progenitor cell activity and genome-wide target gene regulation. These studies will uncover the molecular and cellular mechanism by which SOX3 controls spermatogenesis and provide unique insight into how a single TF controls context-dependent differentiation in sperm versus brain progenitor cells.Read moreRead less