Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.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
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
Evolution and the immune system: genetic differences in immune response between human populations due to adaptation to living in different geo-climatic locations. The project, which investigates the genetics of inter-population differences in immune response, will lead to advances in immunology and population genetics research, explain present population specific differences in disease incidence and possibly forecast future population trends of diseases such as asthma and allergy. The study will ....Evolution and the immune system: genetic differences in immune response between human populations due to adaptation to living in different geo-climatic locations. The project, which investigates the genetics of inter-population differences in immune response, will lead to advances in immunology and population genetics research, explain present population specific differences in disease incidence and possibly forecast future population trends of diseases such as asthma and allergy. The study will strengthen ties with collaborators around the world, thus promoting excellence in Australian research and gain Australia prestige in the international community as a country that produces research of global significance. Understanding the immune system's 'recent evolutionary roots' has implications for the health of Australians, especially in light of Australia's increasingly multi-ethnic background.Read moreRead less
A shipload of consequences: studying the impact of Old World diseases on native South American populations via ancient DNA. This pioneering project will give the first real-time picture of the genetic changes induced by epidemics in human populations. This will reveal important new information about the likely impact of future epidemics on the genetic diversity of the immune system in modern human populations and will be of substantial use in building epidemiological models. By proposing to comb ....A shipload of consequences: studying the impact of Old World diseases on native South American populations via ancient DNA. This pioneering project will give the first real-time picture of the genetic changes induced by epidemics in human populations. This will reveal important new information about the likely impact of future epidemics on the genetic diversity of the immune system in modern human populations and will be of substantial use in building epidemiological models. By proposing to combine state-of-the-art science with global problems of humanity, we will address Australia's interests in expanding scientific expertise beyond its borders and place Australia at the leading edge of disease impact studies.Read moreRead less
Neurovascular pericytes in development and brain regeneration. The brain is responsible for a quarter of the body’s metabolism and is thus perfused by an extensive network of blood vessels. Pericytes surround these vessels and interact with neurons, glia, immune cells and neural stem cells of the neurovascular unit. Pericytes influence brain development, function and regeneration but remain enigmatic. This project investigates molecular control of pericyte development, functional coupling of per ....Neurovascular pericytes in development and brain regeneration. The brain is responsible for a quarter of the body’s metabolism and is thus perfused by an extensive network of blood vessels. Pericytes surround these vessels and interact with neurons, glia, immune cells and neural stem cells of the neurovascular unit. Pericytes influence brain development, function and regeneration but remain enigmatic. This project investigates molecular control of pericyte development, functional coupling of pericytes with adjacent cells and pericyte function in tissue regeneration. We aim to produce new fundamental knowledge in brain development, structure, function and evolution. New knowledge generated here may lead to future approaches in stem cell biology, tissue engineering, regeneration and ageing of the brain. Read moreRead less
The genetics of ageing in human populations. This project aims to test whether genetic differences among individuals influence changes in cognition and physiological function in later life. Differences among individuals, in terms of distinct changes in their physiology as they age, lead to differences in their susceptibility to negative later-life outcomes and ultimately to differences in lifespan. Using a combination of genomic techniques, novel data analysis methods, and the largest dataset of ....The genetics of ageing in human populations. This project aims to test whether genetic differences among individuals influence changes in cognition and physiological function in later life. Differences among individuals, in terms of distinct changes in their physiology as they age, lead to differences in their susceptibility to negative later-life outcomes and ultimately to differences in lifespan. Using a combination of genomic techniques, novel data analysis methods, and the largest dataset of its kind, the project intends to identify the genomic regions and biochemical pathways associated with these changes, and to test for genetic associations between early-life reproduction and later-life outcomes. This is crucial to understanding, predicting and managing transitions across different human life stages.Read moreRead less
Identification of genes regulating breast cancer progression and metastasis. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last thirty years, many women still die from relapse of the disease. Our goal is to identify genes involved in the regulation of breast cancer progression and metastasis. This may lead to the discovery of druggable molecules for better targeted therapies for patients.
Defining the origin of a cell lineage that surrounds and cleans the brain . The vertebrate brain is responsible for up to a quarter of the body’s metabolism, a metabolic load that produces large amounts of tissue waste and requires an efficient cleaning system. A recent discovery in zebrafish and preliminary data has uncovered a cell type surrounding the brain that derives from vasculature. These cells play fundamental roles in scavenging and clearing tissue wastes. The project aims to investiga ....Defining the origin of a cell lineage that surrounds and cleans the brain . The vertebrate brain is responsible for up to a quarter of the body’s metabolism, a metabolic load that produces large amounts of tissue waste and requires an efficient cleaning system. A recent discovery in zebrafish and preliminary data has uncovered a cell type surrounding the brain that derives from vasculature. These cells play fundamental roles in scavenging and clearing tissue wastes. The project aims to investigate the origins and control of this cell type in zebrafish and mouse brains. This will produce new knowledge in brain development, cellular composition, structure, function and evolution. Outcomes are expected to generate new approaches in stem cell biology, tissue engineering, regeneration and ageing of the brain.Read moreRead less