Mechanism and function of cell asymmetry during cell death. This project aims to investigate how dying cells rearrange their cellular contents to aid their removal.
More than 200 billions cells die daily in the human body. It is critical that dying cells are rapidly cleared as their buildup can interfere with normal tissue functions. This project will use a suite of contemporary molecular/cell biological approaches to study a newly identified process that occurs during cell death. Expected outc ....Mechanism and function of cell asymmetry during cell death. This project aims to investigate how dying cells rearrange their cellular contents to aid their removal.
More than 200 billions cells die daily in the human body. It is critical that dying cells are rapidly cleared as their buildup can interfere with normal tissue functions. This project will use a suite of contemporary molecular/cell biological approaches to study a newly identified process that occurs during cell death. Expected outcomes include a paradigm-shift in understanding the process of cell clearance.
This project is expected to generate fundamental new knowledge of the mechanisms by which dying cells are efficiently removed from tissues. This should provide significant benefits to the cell death and general cell biology fields.Read moreRead less
Mechanisms by which Beclin1 regulates intestinal homeostasis. This project aims to investigate if Beclin1, a protein which has an important and well-accepted role in promoting cell survival through the program of autophagy, has an alternate job mediating trafficking within a cell. Using novel mouse models and innovative techniques, the project aims to demonstrate the physiological importance of this alternate role for Beclin1. Expected outcomes include enhancing Australia's international researc ....Mechanisms by which Beclin1 regulates intestinal homeostasis. This project aims to investigate if Beclin1, a protein which has an important and well-accepted role in promoting cell survival through the program of autophagy, has an alternate job mediating trafficking within a cell. Using novel mouse models and innovative techniques, the project aims to demonstrate the physiological importance of this alternate role for Beclin1. Expected outcomes include enhancing Australia's international research standing, and providing research training for young scientists. Benefits include generation of new knowledge and a rethink of the basis for normal development and diseases where Beclin1 has been implicated.Read moreRead less
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
Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insig ....Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insights into the molecular regulation of how cells orchestrate and integrate cell death pathways. This should provide significant benefits, such as providing the knowledge base needed to improve our abilities to manipulate cell death both in basic research and commercial applications of cell death.Read moreRead less
Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes in ....Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes include new insights into how immune cells and tissues respond according to the posing threat. Project benefits include understanding how to manipulate danger responses for future basic research and commercial applications, and fundamental understanding of how animals flourish in a dangerous world.Read moreRead less
Dynamics of mitochondrial cristae in life and death . This application seeks to use innovative approaches to address how massive structural arrangements in mitochondria are dealt with during normal cell function, and modulated during cell death. The study builds on discoveries made by a team with world-leading expertise in mitochondrial biology and cell death – and brings innovative, cutting-edge techniques in cell biology, proteomics and imaging. The findings will provide new fundamental insig ....Dynamics of mitochondrial cristae in life and death . This application seeks to use innovative approaches to address how massive structural arrangements in mitochondria are dealt with during normal cell function, and modulated during cell death. The study builds on discoveries made by a team with world-leading expertise in mitochondrial biology and cell death – and brings innovative, cutting-edge techniques in cell biology, proteomics and imaging. The findings will provide new fundamental insights into cellular organisation and uncover new principles of communication. Trainees will gain skills in technologies that are highly translatable and in demand in other areas of scientific endeavours. As such the expertise obtained will expand Australian research capabilities.
Read moreRead less
How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pat ....How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pathways required for enucleation. The project will provide a molecular and cellular road map of enucleation that may be utilised to enhance the bulk therapeutic in vitro production of red blood cells for veterinary and human purposes.Read moreRead less
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. 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
Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework f ....Making muscle: molecular dissection of membrane domain formation. For a muscle to contract efficiently in response to an electrical signal it requires the formation of an extensive system of hollow membranous tubules through which the signal can be propagated. This proposal addresses the molecular mechanisms involved in the formation of this tubule system in skeletal muscle. This project will develop cell biology in a whole organism rather than a cell culture system and provide a new framework for Australian and international cell biologists. It will generate new knowledge, train young Australian scientists, help build international collaborative networks and engage the public outside the research community.Read moreRead less