Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and ....Molecular determinants of inflammatory caspase activity upon inflammasomes. Most processes fundamental to life rely on the timely, and regulated, execution of cellular functions. The innate immune system, in which both timing and regulation is paramount, rapidly detects invading microbes and induces a measured and timely antimicrobial response to clear infection. This project aims to address a key knowledge gap by characterising a mechanism for timely and controlled immune system activation and immune cell death via the non-canonical inflammasome. We do not currently understand how some immune pathways are turned on or off. This project will yield fundamental insight into mechanisms of mammalian inflammasome, inflammation and anti-microbial responses.Read moreRead less
Links between DNA replication and chromosome end maintenance. This project aims to increase knowledge of the way in which cells maintain their genomes, including the ends of their chromosomes, to enable their own survival. The ends of chromosomes (telomeres) are essential for survival and proliferation of the cells of most organisms. This project aims to determine the molecular details of a recently discovered link between telomere maintenance and the way cells maintain the integrity of their ge ....Links between DNA replication and chromosome end maintenance. This project aims to increase knowledge of the way in which cells maintain their genomes, including the ends of their chromosomes, to enable their own survival. The ends of chromosomes (telomeres) are essential for survival and proliferation of the cells of most organisms. This project aims to determine the molecular details of a recently discovered link between telomere maintenance and the way cells maintain the integrity of their genome. This is likely to lead to increased understanding of the fundamental biological process of genome maintenance, representing a significant scientific advance. The project expects to have far-reaching implications for biotechnology applications that require the survival of cells.Read moreRead less
A molecular timer for inflammation and cell death. This project aims to improve our understanding of the timely function of the immune system. Most processes fundamental to life rely on the timely execution of cellular functions. One biological system in which timing is paramount is the immune system. Organismal health relies upon this front-line defence system for rapidly detecting invading microbes and inducing an appropriate, and timely, antimicrobial response to clear infection. We do not cu ....A molecular timer for inflammation and cell death. This project aims to improve our understanding of the timely function of the immune system. Most processes fundamental to life rely on the timely execution of cellular functions. One biological system in which timing is paramount is the immune system. Organismal health relies upon this front-line defence system for rapidly detecting invading microbes and inducing an appropriate, and timely, antimicrobial response to clear infection. We do not currently understand how immune responses are temporally coordinated. This proposal aims to address this key knowledge gap by characterising a novel molecular timer that dictates the co-ordinated timing of immune responses and immune cell death. These studies may yield fundamental insight into mammalian anti-microbial mechanisms.Read moreRead less
Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein function ....Cellular Responses to Adversity: Oxidative Stress and Protection Against Oxidative Damage. A deficiency in the protein haem oxygenase-1 causes severe biological consequences in animals and humans. These include decreased reproduction, retarded development, the inability of the body to handle iron, chronic inflammation and increased susceptibility to age-associated diseases. This study will determine how a deficiency of the protein alters cells at the level of genes, proteins and protein functions. By doing so, the project will illuminate how haem oxygenase-1 alters cell functions in a beneficial way. This information will eventually assist in preventing the serious disorders associated with deficiency of haem oxygenase-1. It will also provide the basis for novel treatments to slow down age-associated diseases.Read moreRead less
Angiogenic defects in mutant growth plate cartilage reveal new modulators of vascular invasion. Converting cartilage to bone requires blood vessel invasion from the bony interface. This project will test, in vitro and in vivo, the hypothesis that collagen fragments regulate blood vessel invasion into cartilage. This data will have implications for processes requiring new blood vessels such as bone growth, cancer, inflammation and ischemia.
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.Read moreRead less
Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ....Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ageing as well as suppress age onset diseases that include obesity diabetes cardiovascular disease hypertension and neurodegeneration.Read moreRead less
Systems therapeutics for metabolism: AMPK isoform specific drugs. Living cells have to maintain a steady balance between energy production and consumption in order to function properly. A key regulator of energy balance is an enzyme known as 5' AMP-activated protein kinase (AMPK), which regulates the burning and storage of fuels such as fat and sugars, in response to changes in energy demand. This project will provide a major advancement in our understanding of the regulation of AMPK at the mo ....Systems therapeutics for metabolism: AMPK isoform specific drugs. Living cells have to maintain a steady balance between energy production and consumption in order to function properly. A key regulator of energy balance is an enzyme known as 5' AMP-activated protein kinase (AMPK), which regulates the burning and storage of fuels such as fat and sugars, in response to changes in energy demand. This project will provide a major advancement in our understanding of the regulation of AMPK at the molecular level, and lay the foundations for the development of more effective drugs to treat energy balance disorders such as obesity and Type 2 diabetes. Furthermore, this proposal will contribute to enriching Australia's international profile and competitiveness in this important area of research.Read moreRead less
Novel mass spectrometry methods to assess cellular oxidative stress. This project will provide fundamental understanding to the biology of cell stress that may lead to novel approaches for treating age-related diseases. It has the potential to have a significant economic and social impact nationally and internationally and provide Australian scientists with new technologies to study challenging issues in biology.
Isolation and analysis of novel caspases. Apoptosis is an evolutionarily conserved cellular process which must be tightly controlled for normal development and to avoid disease. Rapid progress has been made recently in the elucidation of apoptotic pathways, but many important components are likely still unknown. The caspases constitute the effector arm of apoptotic signalling pathways and some members play important roles in cytokine maturation. We aim to identify novel caspases using an innovat ....Isolation and analysis of novel caspases. Apoptosis is an evolutionarily conserved cellular process which must be tightly controlled for normal development and to avoid disease. Rapid progress has been made recently in the elucidation of apoptotic pathways, but many important components are likely still unknown. The caspases constitute the effector arm of apoptotic signalling pathways and some members play important roles in cytokine maturation. We aim to identify novel caspases using an innovative technique, and to characterise their function and regulation. Molecules identified in this project may be candidate targets for therapies which modulate apoptosis for treatment or prevention of disease, or diagnostic reagent development.Read moreRead less