Genetics of longevity and the delay of post-reproductive senescence. Ageing of the population in the coming decades will cause an increasing health care burden. Diseases of ageing such as Alzheimer's, heart disease, Parkinson's and a range of cancers, as well as impairments of ageing such as reduced mobility and cognitive ability are all caused or exacerbated by oxidative stress. With some exceptions, current medical practices focus on surgical repair or drug therapy to alleviate symptoms of ag ....Genetics of longevity and the delay of post-reproductive senescence. Ageing of the population in the coming decades will cause an increasing health care burden. Diseases of ageing such as Alzheimer's, heart disease, Parkinson's and a range of cancers, as well as impairments of ageing such as reduced mobility and cognitive ability are all caused or exacerbated by oxidative stress. With some exceptions, current medical practices focus on surgical repair or drug therapy to alleviate symptoms of ageing rather than addressing the physiological causes of ageing itself. Our project will provide understanding of natural systems that prevent age-related senescence due to oxidative stress. The goal is to identify novel and natural ways to maximise the fitness, well-being and self-sufficiency of people as they age.Read moreRead less
An epigenetic basis for foetal programming. The social and economic impact of adult-onset diseases such as diabetes, hypertension and atherosclerosis is increasing. Evidence indicates that a mother's nutrition influences the risk of her children developing some diseases later in life. This proposal aims to elucidate the mechanism underlying this phenomenon. By understanding the mechanism through which maternal nutrition affects disease risk, we may make it possible to design early diagnosis and ....An epigenetic basis for foetal programming. The social and economic impact of adult-onset diseases such as diabetes, hypertension and atherosclerosis is increasing. Evidence indicates that a mother's nutrition influences the risk of her children developing some diseases later in life. This proposal aims to elucidate the mechanism underlying this phenomenon. By understanding the mechanism through which maternal nutrition affects disease risk, we may make it possible to design early diagnosis and intervention strategies. Our work may suggest intervention strategies - such as supplementation of at-risk mothers with key molecules such as methyl donors - during foetal and early postnatal life, which could be key to preventing premature morbidity and mortality.Read moreRead less
The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these ....The effect of mitochondrial and nuclear-cytoplasmic variation on longevity, metabolism and stress resistance in Drosophila. Much research points to a major role of free radical damage in aging, thus the belief that antioxidants might be beneficial in delaying aging. Free radicals are mostly formed in the subcellular organelles which consume oxygen and produce energy, and this may be the major site of age-related damage. This project seeks to understand the degree to which variation among these subcellular organelles affect free radical damage and aging, using the fruitfly Drosophila melanogaster as a model organism.Read moreRead less
The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between ....The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between plasma proteins and apoE, which is a lipid-binding protein genetically linked to age-related diseases affecting more than 500,000 Australians. This project will therefore provide scope for novel treatments and early detection of disease, namely cardiovascular and Alzheimer's disease.Read moreRead less
Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence micro ....Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence microscopy and digital imaging technologies for studying multicellular tissues such as skeletal muscle will enhance the international competitiveness of Australian biological research. The research will optimise development of gene delivery systems that may find eventual application for muscle wasting disorders and conditions where muscle weakness compromises quality of life.Read moreRead less
Regulation of cell surface sialylation by targeting the CMP-sialic acid transporter and sialyltransferase: Towards the development of anti-metastatic agents. The mortality rates for many of the cancers afflicting the world's population are mirrored in Australia, particularly colon cancer. It's generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue in this country, representing a major challenge to biomedical researchers and healthcare professional. The e ....Regulation of cell surface sialylation by targeting the CMP-sialic acid transporter and sialyltransferase: Towards the development of anti-metastatic agents. The mortality rates for many of the cancers afflicting the world's population are mirrored in Australia, particularly colon cancer. It's generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue in this country, representing a major challenge to biomedical researchers and healthcare professional. The economic and social impact is immense, placing a huge strain on the healthcare system, as well as on the families affected. Any alternative treatment reducing cancer metastasis would be of enormous national and international benefit. It's believed that the significant studies outlined in this proposal, which are based on exciting preliminary data, will make a sizeable contribution to achieving this goal.Read moreRead less
The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will presen ....The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will present a medical and economic challenge demanding novel and powerful science. This research will lead both to deeper understanding of the basic mechanisms underlying such disorders and to tools for designing new and effective treatments.
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Novel compounds to disrupt protein-protein interactions. Many diseases involve aberrant interactions between proteins. Strategies to inhibit such interactions have potential as tool reagents for biological research but also as new therapies. Most drugs currently used in the clinic are small organic molecules, though these typically are not effective at disrupting protein complexes, hence alternatives are required. This proposal to examine foldamers as a novel strategy for inhibiting protein: pro ....Novel compounds to disrupt protein-protein interactions. Many diseases involve aberrant interactions between proteins. Strategies to inhibit such interactions have potential as tool reagents for biological research but also as new therapies. Most drugs currently used in the clinic are small organic molecules, though these typically are not effective at disrupting protein complexes, hence alternatives are required. This proposal to examine foldamers as a novel strategy for inhibiting protein: protein interactions could lead to the development of new drugs for the treatment of diseases where the current traditional approaches have proven ineffective.Read moreRead less
The role of short tandem repeat DNA variation in the evolution of human psychological diversity. The proposed work addresses fundamental questions about human nature. It ties together the evolutionary processes that have shaped us as a species with the way our genes influence: our personalities, the way we think and how we behave. It introduces a novel approach to addressing questions about the role of genetics in human variation that will contribute substantially to the way we understand, perce ....The role of short tandem repeat DNA variation in the evolution of human psychological diversity. The proposed work addresses fundamental questions about human nature. It ties together the evolutionary processes that have shaped us as a species with the way our genes influence: our personalities, the way we think and how we behave. It introduces a novel approach to addressing questions about the role of genetics in human variation that will contribute substantially to the way we understand, perceive and manage important aspects of human diversity.Read moreRead less
Genetics of Postmenopausal Bone Loss. The major consequence of bone loss in our ageing society is fracture. At 50 years for women, the lifetime risk of sustaining an osteoporotic fracture is 50%. The consequences of these fractures, which can include reduced life expectancy, prolonged medical care, and loss of independence, have a profound socioeconomic impact in an ageing population. The proposed study offers a unique opportunity to examine the contribution of genetic factors to postmenopausal ....Genetics of Postmenopausal Bone Loss. The major consequence of bone loss in our ageing society is fracture. At 50 years for women, the lifetime risk of sustaining an osteoporotic fracture is 50%. The consequences of these fractures, which can include reduced life expectancy, prolonged medical care, and loss of independence, have a profound socioeconomic impact in an ageing population. The proposed study offers a unique opportunity to examine the contribution of genetic factors to postmenopausal osteoporosis.Read moreRead less