Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
Going with the flow: directing nutrient rich blood to the brain. This project aims to visualise and measure flow of blood from the umbilical cord to the fetal brain and to understand how delivery of oxygen and glucose to the brain is prioritised by constriction or relaxation of a specialised shunt, the ductus venosus. The project will directly and non-invasively measure this fundamental phenomenon with novel MRI protocols. Expected outcomes of this project include advances in measuring fetal blo ....Going with the flow: directing nutrient rich blood to the brain. This project aims to visualise and measure flow of blood from the umbilical cord to the fetal brain and to understand how delivery of oxygen and glucose to the brain is prioritised by constriction or relaxation of a specialised shunt, the ductus venosus. The project will directly and non-invasively measure this fundamental phenomenon with novel MRI protocols. Expected outcomes of this project include advances in measuring fetal blood flow and the exchange of expertise between leading researchers in Australia and Canada. In the long-term, this will enhance Australia’s research capacity in fetal physiology and may lead to new tools for monitoring or supporting fetal development.Read moreRead less
Opening and closing doors in the fetal circulation impacts brain metabolism. This project aims to measure blood flow from the umbilical cord through special shunts or doors to the fetal brain and to understand how changes in delivery of oxygen may impact fetal brain metabolism. This fundamental phenomenon will be measured with novel MRI protocols developed by a multidisciplinary, international team. Expected outcomes of this project include world-leading advances in measuring fetal blood flow ....Opening and closing doors in the fetal circulation impacts brain metabolism. This project aims to measure blood flow from the umbilical cord through special shunts or doors to the fetal brain and to understand how changes in delivery of oxygen may impact fetal brain metabolism. This fundamental phenomenon will be measured with novel MRI protocols developed by a multidisciplinary, international team. Expected outcomes of this project include world-leading advances in measuring fetal blood flow and brain metabolism with exchange of expertise between leading researchers in Australia and Canada and their trainees. In the long-term, this should provide significant benefits in enhancing Australia’s research capacity in fetal physiology and may lead to new tools for monitoring or supporting fetal development.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
Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how t ....Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how the atypical cadherin FAT4 relays mechanical signals including flow and tension to the lymphatic endothelial cell skeleton, thereby enabling changes in cell shape important for building lymphatic vessels. This project will increase our understanding of how cells sense touch and may be applied for tissue engineering purposes.
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Understanding the mechanisms that inhibit and promote biofilm expansion. Yeasts have been used for biotechnology throughout recorded history. They are important human pathogens, and major experimental models of eukaryotic cells. Although yeasts are some of the most studied organisms in biology, their modes of colony biofilm formation are not fully understood. Methods to investigate the environmental and genetic processes that drive colony biofilm formation will be developed in this proposed pro .... Understanding the mechanisms that inhibit and promote biofilm expansion. Yeasts have been used for biotechnology throughout recorded history. They are important human pathogens, and major experimental models of eukaryotic cells. Although yeasts are some of the most studied organisms in biology, their modes of colony biofilm formation are not fully understood. Methods to investigate the environmental and genetic processes that drive colony biofilm formation will be developed in this proposed project. They will provide a deeper understanding of the mechanisms that inhibit and promote biofilm formation, and colonial morphology in the different modes of growth of Saccharomyces cerevisiae, with implications for this and other biofilm-forming yeasts of biotechnological or medical importance.Read moreRead less
Quantifying yeast cell mechanisms: filamentous growth and biofilm formation. This project aims to quantify the cellular mechanisms of yeast growth to advance our understanding of these organisms and support strategies to prevent and treat disease. Although yeasts are some of the most studied organisms in biology, their modes of filamentous growth and biofilm formation are not fully understood. Yeasts such as the Candida species cause potentially lethal infections through filamentous invasion of ....Quantifying yeast cell mechanisms: filamentous growth and biofilm formation. This project aims to quantify the cellular mechanisms of yeast growth to advance our understanding of these organisms and support strategies to prevent and treat disease. Although yeasts are some of the most studied organisms in biology, their modes of filamentous growth and biofilm formation are not fully understood. Yeasts such as the Candida species cause potentially lethal infections through filamentous invasion of tissues. The project plans to develop methods to quantify the mechanisms driving these growth processes. These methods will be designed to permit classification and selection of strain-specific properties of yeasts, providing a deeper understanding of the mechanisms controlling cellular and colonial morphology in the growth of Saccharomyces cerevisiae, the most important yeast in both biotechnology and bioscience.Read moreRead less
New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong c ....New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong collaborative team and highly innovative approaches, the project will generate new knowledge to inform how cells communicate. Expected outcomes include knowledge of broad significance to cell biology, that can be leveraged to develop extracellular vesicles as tools for various biotechnology applications in the future.Read moreRead less
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.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.