The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Fur ....The effects of alpha-2-macroglobulin on amyloid formation and toxicity. The expected outcomes will provide major advances in understanding how the abundant human blood protein alpha-2-macroglobulin influences the formation of protein aggregates that underpin a number of serious diseases (e.g. Alzheimer's disease). The linkages involved are of the highest calibre and will give the Fellowship holder a unique opportunity for training in environments that are truly internationally leading-edge. Furthermore, the very high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to international research outcomes of the highest quality.Read moreRead less
Establishing the role of alpha-2-macroglobulin in quality control of extracellular protein folding. The expected outcomes will provide important advances in understanding the role of alpha-2-macroglobulin (A2M) in maintaining the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad si ....Establishing the role of alpha-2-macroglobulin in quality control of extracellular protein folding. The expected outcomes will provide important advances in understanding the role of alpha-2-macroglobulin (A2M) in maintaining the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to world research outcomes. This project will also provide a direct social benefit by training research students with the skills necessary to further the development of biological research in Australia.Read moreRead less
Discovering Mechanisms for Quality Control of Extracellular Protein Folding. The expected outcomes will provide important advances in understanding of how the mammalian body maintains the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad significance of this work indicate that it w ....Discovering Mechanisms for Quality Control of Extracellular Protein Folding. The expected outcomes will provide important advances in understanding of how the mammalian body maintains the normal structure/function of extracellular proteins. This information may ultimately aid in the design of agents to be used to clear the body of pathological protein aggregates - potentially providing a direct economic benefit to Australia. The high novelty and broad significance of this work indicate that it will produce high-impact publications which will tangibly assist Australia being recognized as a major contributor to world research outcomes. This project will also provide a direct social benefit by training research students with the skills necessary to further the development of biological research in Australia. Read moreRead less
Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal w ....Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal will receive international recognition and will encourage more research in this field, attracting international funding, and create new research opportunities. Read moreRead less
Biomaterial applications of synthetic elastin. The grant will develop a new collaboration between two established laboratories. The Weiss Lab (synthetic elastin; University of Sydney, Australia) will send elastin materials to the Langer Lab (interface of biotechnology and materials science; MIT, USA). Prof. Weiss will visit the Langer Lab and be trained in and participate collaboratively in the use of established MIT methodologies that will focus on applications in cardiac tissue engineering, co ....Biomaterial applications of synthetic elastin. The grant will develop a new collaboration between two established laboratories. The Weiss Lab (synthetic elastin; University of Sydney, Australia) will send elastin materials to the Langer Lab (interface of biotechnology and materials science; MIT, USA). Prof. Weiss will visit the Langer Lab and be trained in and participate collaboratively in the use of established MIT methodologies that will focus on applications in cardiac tissue engineering, controlled release of drugs and vocal fold repair. The MIT group will benefit from access to and the use of elastin materials that are developed in AustraliaRead moreRead less
Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will lear ....Biochemistry of tropoelastin and elastin: the molecular architecture of elastic fibre assembly. Elastin destruction drives the progression of emphysema, a major component of chronic obstructive pulmonary disease which is a major cause of death. Loss of elastin leads to profound blockage of arteries. If we are to treat these problems we need to know how to make and repair elastin. This research will enable us to discover how elastin is constructed and define its interacting partners. We will learn how to make tissue components found in parts of the body that expand and contract such as the arteries, lung and skin. We will learn about the molecular mechanisms of elastin assembly and cell interactions, which gives us the core molecular toolkit to repair elastin tissue.Read moreRead less
Fruit fly pests in northwestern Australia: invasion, hybridisation or evolution? In northwestern Australia, recent events suggest that a new and serious fruit fly pest is now present, wher previously none existed. Due to difficulties in accurate identification, we do not know whether these new pest fruit flies are endemic fruit flies that have changed their behaviour, invasions of Queensland fruit fly, or hybrids between them. This project will use DNA microsatellites to distinguish between th ....Fruit fly pests in northwestern Australia: invasion, hybridisation or evolution? In northwestern Australia, recent events suggest that a new and serious fruit fly pest is now present, wher previously none existed. Due to difficulties in accurate identification, we do not know whether these new pest fruit flies are endemic fruit flies that have changed their behaviour, invasions of Queensland fruit fly, or hybrids between them. This project will use DNA microsatellites to distinguish between these possibilities. It will also establish whether the different species involved are actually different species, or should be regarded merely as different races. Such distinctions are important both scientifically and for export quarantine purposes.Read moreRead less
Determinants of metabolic rate in animals. The metabolic rate of an animal represents its fundamental "cost of living" and varies dramatically (>100-fold) between different vertebrate species. We have proposed the "membrane pacemaker theory" to explain this variation and currently this is the only mechanistic explanation of metabolic variation between species. It has received significant international interest. A species metabolic rate and its maximum lifespan are connected but the precise mecha ....Determinants of metabolic rate in animals. The metabolic rate of an animal represents its fundamental "cost of living" and varies dramatically (>100-fold) between different vertebrate species. We have proposed the "membrane pacemaker theory" to explain this variation and currently this is the only mechanistic explanation of metabolic variation between species. It has received significant international interest. A species metabolic rate and its maximum lifespan are connected but the precise mechanistic link between them is unknown. We will investigate the mechanisms underlying the "membrane pacemaker theory" as an explanation of the metabolic rates of vertebrate species and its role in the determination of maximum lifespan.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
Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also p ....Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also provides the source material for exploitation of bacterial products such as antibiotics. The results from understanding a complete set of mutational changes through genomic analysis will provide the most direct estimates of variation in evolving bacteria.Read moreRead less