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
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
Discovery Early Career Researcher Award - Grant ID: DE240101286
Funder
Australian Research Council
Funding Amount
$469,707.00
Summary
SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover t ....SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover the role of SARS-CoV-2-induced dead cell fragmentation in promoting viral uptake and inflammation. Its findings should provide significant scientific, health and economic benefits by informing new research directions on infection and innate immunity as well as future therapeutic designs for infection treatment.Read moreRead less
Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Exp ....Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Expected outcomes encompass a paradigm-shift in understanding how cells that line the blood vessels dispose unwanted cellular contents. This should provide significant benefits including understanding how these specialised cells maintain the integrity of blood vessels and communicate with immune cells.Read moreRead less
How do unconventional T cells die? Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells ....How do unconventional T cells die? Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling T cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.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.
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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
Defining how signalling pathways cooperate to regulate organ size. Control of organ size is essential for organ function and organism viability, and varies greatly across the animal kingdom. This project aims to understand how three important signalling pathways co-ordinately regulate organ size during development and also limit aberrant growth. By applying genomics, genetics and bioinformatics techniques, this project aims to discover a core set of growth genes that are regulated by different s ....Defining how signalling pathways cooperate to regulate organ size. Control of organ size is essential for organ function and organism viability, and varies greatly across the animal kingdom. This project aims to understand how three important signalling pathways co-ordinately regulate organ size during development and also limit aberrant growth. By applying genomics, genetics and bioinformatics techniques, this project aims to discover a core set of growth genes that are regulated by different signalling pathways and the mechanism by which transcription of these genes is repressed in order to eliminate faulty cells. Intended benefits are creation of jobs, new knowledge on fundamental principles of life and the stimulation of new research into organ size control.Read moreRead less
How are sperm mitochondria eliminated after fertilisation . The fact that mitochondria are inherited exclusively through the maternal germ-line is fundamental feature of sexual reproduction in all but a few organisms. This uni-parental inheritance is thought to prevent genetic conflict between different mitochondrial genomes. The mechanisms controlling uniparental inheritance involve eliminating the sperm mitochondria soon after fertilisation. We will investigate 2 possible mechanisms, (1) acti .... How are sperm mitochondria eliminated after fertilisation . The fact that mitochondria are inherited exclusively through the maternal germ-line is fundamental feature of sexual reproduction in all but a few organisms. This uni-parental inheritance is thought to prevent genetic conflict between different mitochondrial genomes. The mechanisms controlling uniparental inheritance involve eliminating the sperm mitochondria soon after fertilisation. We will investigate 2 possible mechanisms, (1) active destruction and (2) passive dilution. The results will help explain how heteroplasmy is avoided in order to maintain the fitness of organisms including animals and humans. The results will have long term insights into improving breeding in agriculture and in the prevention of mitochondrial genetic disease.Read moreRead less