Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family protei ....Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family proteins in spermatogenesis. The outcomes will define the different roles of highly similar proteins from the same family in differentiation of a single cell lineage. This is important in generating functional tissues using in vitro laboratory approaches or understanding how normal development and developmental disorders arise.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
Mechanism and function of dying cell disassembly. This project aims to elucidate the molecular machinery that disassembles dying cells, and the role of this process in cell clearance. Billions of cells in the body die daily as part of normal turnover. Dying cells must be rapidly removed, as their accumulation can interfere with normal tissue functions. To efficiently clear dead cells, dying cells can disassemble into smaller fragments that neighbouring cells engulf. Understanding the mechanistic ....Mechanism and function of dying cell disassembly. This project aims to elucidate the molecular machinery that disassembles dying cells, and the role of this process in cell clearance. Billions of cells in the body die daily as part of normal turnover. Dying cells must be rapidly removed, as their accumulation can interfere with normal tissue functions. To efficiently clear dead cells, dying cells can disassemble into smaller fragments that neighbouring cells engulf. Understanding the mechanistic basis and function of dying cell disassembly is expected to generate knowledge of the downstream consequence of cell death. This breakthrough will be important in many fields of research including cell biology and biochemistry, and generate basic knowledge that can ultimately be applied in medical science to understand or treat pathological conditions associated with cell death.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
Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioi ....Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioinformatics to dissect the functions of the lymphoid stromal cells and their roles in the swelling of lymphoid tissues during immune responses. This will provide vital information about the biology of these understudied cells and reveal the ways in which they support the generation of immunity.Read moreRead less
Understanding the diverse biology of CD4+ T cell resident memory. This project aims to examine the biology of CD4 T cell memory in tissues. The previously unappreciated complexity of the CD4 T cell resident memory compartment in the liver will be characterised, focusing on the generation, maintenance and diversity of functions of these cells. Expected outcomes include the generation of fundamental knowledge in the disciplines of cellular biology and immunology, and unique, highly specialised stu ....Understanding the diverse biology of CD4+ T cell resident memory. This project aims to examine the biology of CD4 T cell memory in tissues. The previously unappreciated complexity of the CD4 T cell resident memory compartment in the liver will be characterised, focusing on the generation, maintenance and diversity of functions of these cells. Expected outcomes include the generation of fundamental knowledge in the disciplines of cellular biology and immunology, and unique, highly specialised student and personnel training through the interdisciplinary approach utilised, which spans cellular biology, live-imaging and transcriptomic analyses. Expected benefits include influential publications and the import of a novel, specialised technique to Australia through an international collaboration (Germany)Read moreRead less
Investigating the activator function of the Bim protein. Apoptosis is a research area where Australia has had long standing success. The first observations of this important process were made by Prof John Kerr in the 60's and 70's. A molecular renaissance developed in the late 80's and has led to the current explosion in this area of research. Many of these recent studies have been conducted at the Walter and Eliza Hall Institute. Our scientific endeavour is aimed at broadening the understanding ....Investigating the activator function of the Bim protein. Apoptosis is a research area where Australia has had long standing success. The first observations of this important process were made by Prof John Kerr in the 60's and 70's. A molecular renaissance developed in the late 80's and has led to the current explosion in this area of research. Many of these recent studies have been conducted at the Walter and Eliza Hall Institute. Our scientific endeavour is aimed at broadening the understanding of the mechanisms of cell death using genetically modified mouse models. Insights gained through this project will have far reaching implications for the design of new drugs to combat cancer and degenerative diseases.Read moreRead less
A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune ....A cellular hub for the organisation of T cell priming. This project aims to delineate the cellular interactions involved in the initiation of immune responses by utilising advanced in vivo imaging. Adaptive immunity in vertebrates functions via the acquisition of signals by immune cells via complex interactions with other immune cells, yet these exchanges are difficult to observe and define. This project expects to provide insights into the mechanisms that underpin effective cell-mediated immune responses. The expected outcomes are to generate fundamental new knowledge about immune responses and enhance capacity to study the immune system. This could benefit future development of new vaccines and therapies to improve health.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
Mechanisms connecting diet, metabolism, gut microbiota and immunity. This project will identify the role of short chain fatty acids and the G-protein coupled receptor (GPR43) in regulating immune responses. This could explain how diet affects immune responses and also how certain bacteria in the gut provide benefits for immune defence.