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
Normal heart development before birth. This project aims to understand how the fetal heart can develop normally with much less oxygen than an adult heart uses. Regulation of fetal heart proliferation is not well understood but changes in oxygen levels and non-coding RNAs are implicated. Using advanced imaging techniques to measure blood flow in blood vessels to the fetal heart and molecular probes to assess cell function and microarrays to measure non-coding RNA, the project expects to generate ....Normal heart development before birth. This project aims to understand how the fetal heart can develop normally with much less oxygen than an adult heart uses. Regulation of fetal heart proliferation is not well understood but changes in oxygen levels and non-coding RNAs are implicated. Using advanced imaging techniques to measure blood flow in blood vessels to the fetal heart and molecular probes to assess cell function and microarrays to measure non-coding RNA, the project expects to generate new knowledge about mechanisms of fetal heart cell proliferation. Ultimately, this new knowledge could lead to non-invasive approaches to detect and treat abnormal fetal heart growth in animals and humans.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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The molecular interactome and functions of circular RNAs. This project aims to identify the functions of circular RNAs, the most contemporary and enigmatic family of RNA molecules. While their abundance suggests they are important, it is unclear how they function at the molecular level. This project aims to delineate circular RNA function by systematically identifying their interacting partners at the DNA, RNA and protein levels, the so-called molecular interactome. This project will reprogram e ....The molecular interactome and functions of circular RNAs. This project aims to identify the functions of circular RNAs, the most contemporary and enigmatic family of RNA molecules. While their abundance suggests they are important, it is unclear how they function at the molecular level. This project aims to delineate circular RNA function by systematically identifying their interacting partners at the DNA, RNA and protein levels, the so-called molecular interactome. This project will reprogram embryonic stem cells to model developmental processes and is designed to validate circular RNA research. Together, the benefits include a higher-quality research workforce by mentoring students, refining fundamental tenets of RNA biology and may extend to improving health in the long-term.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100604
Funder
Australian Research Council
Funding Amount
$436,600.00
Summary
How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to ....How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to improve our comprehension of how cells respond to force. The expected outcome is a greater understanding of mechanical and biochemical relationships between cells and the environment, to inform fields of tissue engineering of culture scaffolds to better mimic natural cell-tissue settings.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
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