Production Of Humanised Mouse Models For Haemoglobin E And 0-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$280,693.00
Summary
The proposed study aims to identify and characterise genes critical to male fertility using two mouse models of infertility: 1) Joey mouse line: an ENU induced model of sperm abnormalities. Following linkage analysis, candidate genes will be selected for sequencing to identify the causal mutation. 2) Ggn knockout mice. The role of the testis-specific gene, Ggn will be characterised through a phenotypic analysis of Ggn knockout mice and a series of expression and biochemical analyses. Both models ....The proposed study aims to identify and characterise genes critical to male fertility using two mouse models of infertility: 1) Joey mouse line: an ENU induced model of sperm abnormalities. Following linkage analysis, candidate genes will be selected for sequencing to identify the causal mutation. 2) Ggn knockout mice. The role of the testis-specific gene, Ggn will be characterised through a phenotypic analysis of Ggn knockout mice and a series of expression and biochemical analyses. Both models will be of direct value in the identification of commercially relevant contraceptive targets, as well as furthering our understanding of male reproductive function.Read moreRead less
Sino-Australian neurogenetics initiative. This project will undertake large population studies to identify genes that are associated with motor neuron disease, schizophrenia and intracranial haemorrhage. The project will determine genetic markers, aid development of diagnostic tools and identify new therapeutic targets for these common heritable neurological diseases.
Detection Of Alternative Lengthening Of Telomeres In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate ....In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate themselves many times, and therefore they need to find a method to prevent their telomeres shortening. We discovered one such method, called Alternative Lengthening of Telomeres (ALT), that is used by some cancers. It has been shown in principle that cancer cells can be killed by disrupting their ability to prevent telomere shortening. Therefore, in another project we are developing methods needed to find drugs that inhibit ALT. In the meantime, we have found the first evidence that some normal cells have an ALT-like mechanism. Our speculation is that cancer cells are able to dysregulate and subvert this normal mechanism in order to prevent their telomeres from shortening. In this project, we will analyse the ALT-like mechanism in mice, to determine its characteristics, and to determine what tissues use it. This information will provide critically important insights into the ALT mechanism itself, and the likely side effects of drugs that inhibit ALT.Read moreRead less
Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understan ....Investigating differences in decision-making ability in older adults. This project aims to investigate how healthy ageing impacts decision making and its associated neural circuits using computation modelling and neurogenetic methods. Decision-making is a fundamental cognitive ability, allowing us to choose the best course of action. This project will investigate the relationship between genes and decision-making performance across the adult lifespan. Expected outcomes include a deeper understanding of how decision-making evolves in healthy ageing, and a tool based on genetic scores and computational modelling to predict an individual's trajectory of cognitive function. This could help identify individuals who are at risk for cognitive decline, which could then inform better interventions.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
Discovery Early Career Researcher Award - Grant ID: DE220100230
Funder
Australian Research Council
Funding Amount
$365,000.00
Summary
Investigating the Genetic Basis of Human Intrinsic Capacity. Intrinsic capacity is a new concept introduced by experts at the World Health Organisation to promote healthy ageing. It is defined as the composite of an individual’s physical and mental capacities, based on measures of five criteria; cognitive, sensory, locomotor, vitality and psychological. It is a genetically predetermined trait, but is influenced by a range of environmental stimuli. Applying a cutting-edge genetic methodology on b ....Investigating the Genetic Basis of Human Intrinsic Capacity. Intrinsic capacity is a new concept introduced by experts at the World Health Organisation to promote healthy ageing. It is defined as the composite of an individual’s physical and mental capacities, based on measures of five criteria; cognitive, sensory, locomotor, vitality and psychological. It is a genetically predetermined trait, but is influenced by a range of environmental stimuli. Applying a cutting-edge genetic methodology on big biobank datasets, this project aims to examine the role of genetics and the environment to explain the variability of intrinsic capacity between individuals. Understanding the biological basis of intrinsic capacity has major implications for scientific research in healthy ageing and mental wellbeing.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
Discovery Indigenous Researchers Development - Grant ID: DI0560757
Funder
Australian Research Council
Funding Amount
$160,896.00
Summary
Identification and Characterisation of Genes involved in the Copper Regulation of the Human Alzheimer's Disease Amyloid-Beta Precursor Protein (APP) Gene. Alzheimer's disease (AD) is the most common form of dementia in the ageing population. This research project aims to identify and characterise new genes involved in the copper regulation of the Alzheimer's disease gene. This may lead to the development of novel therapeutic targets and clinical intervention strategies as well as early diagnost ....Identification and Characterisation of Genes involved in the Copper Regulation of the Human Alzheimer's Disease Amyloid-Beta Precursor Protein (APP) Gene. Alzheimer's disease (AD) is the most common form of dementia in the ageing population. This research project aims to identify and characterise new genes involved in the copper regulation of the Alzheimer's disease gene. This may lead to the development of novel therapeutic targets and clinical intervention strategies as well as early diagnostic procedures in preventative healthcare for the treatment of AD. The benefits would affect the international community as a whole, potentially minimising the socio-economic costs arising from the predicted world-wide increase in AD in the ageing population.Read moreRead less