GENOMIC/PHENOMIC IDENTIFICATION AND CHARACTERISATION OF NOVEL HEMATOPOIETIC REGULATORS. Blood cells are fundamental to health. They play a vital role in maintaining the condition of tissues and organs, fight infections and are essential players in the body's response to injury. Understanding how blood cells are produced and how they function is critical to improving the treatment of disease. With the sequencing of the genome, we now have the tools we need to find the genes controlling these proc ....GENOMIC/PHENOMIC IDENTIFICATION AND CHARACTERISATION OF NOVEL HEMATOPOIETIC REGULATORS. Blood cells are fundamental to health. They play a vital role in maintaining the condition of tissues and organs, fight infections and are essential players in the body's response to injury. Understanding how blood cells are produced and how they function is critical to improving the treatment of disease. With the sequencing of the genome, we now have the tools we need to find the genes controlling these processes. This project will harness the power of modern genetic technologies to dissect the role of novel genes involved in blood cell formation and function, and will open up new therapeutic opportunities for treating the many diseases associated with dysregulation of this important cell system. Read moreRead less
Shaping a signal: studies on non-contiguous residues in an intracellular serpin that constitute a novel nuclear protein import signal. Eukaryotic cells contain membrane-bound organelles like the nucleus, endoplasmic reticulum and mitochondria, and use specific mechanisms to direct proteins from their site of synthesis to their target organelle. In nuclear proteins, sequence motifs termed nuclear localization signals (NLSs) direct engagement with the nuclear pore complex and translocation from cy ....Shaping a signal: studies on non-contiguous residues in an intracellular serpin that constitute a novel nuclear protein import signal. Eukaryotic cells contain membrane-bound organelles like the nucleus, endoplasmic reticulum and mitochondria, and use specific mechanisms to direct proteins from their site of synthesis to their target organelle. In nuclear proteins, sequence motifs termed nuclear localization signals (NLSs) direct engagement with the nuclear pore complex and translocation from cytoplasm to nucleus. All NLSs described so far consist of 5-7 contiguous basic residues. We propose to study a novel NLS that we recently discovered on an intracellular serpin. This comprises non-contiguous residues that together form a basic "patch" on the mature protein, and is the first example of a conformational NLS.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.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
Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. ....Regulation of lipolysis: new players, new paradigms. The way in which fat is broken down is poorly understood. This research will determine how important proteins in fat breakdown are turned on and off. By understanding this relationship, effective pharmaceutical treatments will be developed that will enhance the capacity to burn fat and ultimately reduce the incidence of type 2 diabetes and cardiovascular disease, and ease the associated financial burden on the community and healthcare system. Understanding fat breakdown is also important for developing new processing technologies in the food industry.Read moreRead less
Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be dev ....Molecular basis of skeletal muscle lipoapoptosis. High levels of fat in cells are associated with obesity and type 2 diabetes, medical conditions that have increased dramatically in prevalence in Australia. High fat levels in cells also causes cell death. This research will determine the mechanisms by which excessive fat storage leads to cell death and whether this leads to insulin resistance and type 2 diabetes. By understanding this relationship, effective pharmaceutical treatments will be developed that will ultimately reduce the incidence of type 2 diabetes, and ease the associated financial burden on the community and healthcare system.Read moreRead less
Re-uniting marsupials and eutherians by embryonic micromanipulation. The unique responsibility for transmitting life from generation to generation normally depends on the gametes. This project will use new reproductive technologies to investigate the properties of the oocyte in reprogramming somatic cell nuclei, and will use the nuclei of both marsupial and eutherian somatic cells to test this. We will also use both marsupial and eutherian genes to insert into the oocyte to create the first tra ....Re-uniting marsupials and eutherians by embryonic micromanipulation. The unique responsibility for transmitting life from generation to generation normally depends on the gametes. This project will use new reproductive technologies to investigate the properties of the oocyte in reprogramming somatic cell nuclei, and will use the nuclei of both marsupial and eutherian somatic cells to test this. We will also use both marsupial and eutherian genes to insert into the oocyte to create the first transgenic marsupials. We will also investigate the ability of spermatozoa from species of increasing genetic distance to ferttilise marsupial eggs using intracytoplasmic sperm injection (ICSI).Read moreRead less
Mechanisms of cell death regulation by the Bcl-2 protein family. Through the proposed study, the expected outcome is a better understanding of the important process of how the Bcl-2 family of proteins interact with each to control cell death. Furthermore, as dysfunctional apoptosis signalling contributes to diseases such as autoimmune conditions, neurodegenerative disorders and cancer, a detailed and sound understanding of how the cell death machinery operates should enable the design of more ef ....Mechanisms of cell death regulation by the Bcl-2 protein family. Through the proposed study, the expected outcome is a better understanding of the important process of how the Bcl-2 family of proteins interact with each to control cell death. Furthermore, as dysfunctional apoptosis signalling contributes to diseases such as autoimmune conditions, neurodegenerative disorders and cancer, a detailed and sound understanding of how the cell death machinery operates should enable the design of more effective and importantly, safer therapies against these pathologies.Read moreRead less
Functional genetic analysis of wood formation genes in Eucalyptus. Eucalypts are the world's most important plantation hardwood species due to their superior wood characteristics and high growth rates that make them excellent carbon sequestration platforms. Australia is the custodian of the world's natural eucalypt resource and our results will assist in their sustainable use with the potential to transform the national forestry industry by helping to streamline tree improvement efforts. This wi ....Functional genetic analysis of wood formation genes in Eucalyptus. Eucalypts are the world's most important plantation hardwood species due to their superior wood characteristics and high growth rates that make them excellent carbon sequestration platforms. Australia is the custodian of the world's natural eucalypt resource and our results will assist in their sustainable use with the potential to transform the national forestry industry by helping to streamline tree improvement efforts. This will be achieved by increasing our understanding of the development and production of wood, which will lead to increased productivity (more and better quality wood from less land). Custom designed wood also holds much promise for the production of novel biopolymers and as a renewable source for improved biofuels.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less