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The Role Of Nutrition In Disease-linked Epigenetic Inheritance
Funder
National Health and Medical Research Council
Funding Amount
$485,412.00
Summary
This project aims to investigate one mechanism behind fetal programming, in which a suboptimal in utero environment can affect health of offspring in later life. We and others have recently shown that fetal programming can be caused by changes in the way genes behave, and we will examine how many genes are affected by these changes. We will ask whether the changes can increase in frequency with long-term exposure to nutritional stress, and become entrenched within the population.
Epigenetic and neurobehavioural changes in a new mouse model of foetal alcohol spectrum disorders. Foetal alcohol syndrome involves changes in growth, skull structure, central nervous system defects and intellectual disabilities. This project will use a mouse model to study the underlying causes of this disorder, focussing on brain structure and function, and aim to identify markers that can be used for early diagnosis and treatment.
The role of transient DNA methylation on muscular adaptation. Regulation of gene expression is fundamental to all living organisms. This project will utilise the preliminary evidence that DNA methylation, an imprint establishing the phenotype of a specific organ, rapidly drops after an exercise bout, contradicting the dogma that DNA methylation is a locked process.
Extracellular vesicles in the inheritance of acquired traits. This project aims to examine the role of extracellular vesicles (EV) in the transfer of regulatory RNA from somatic cells to germline cells. This project suggests that somatic EVs from the epididymis transfer regulatory RNA to the sperm, and that this RNA exerts its effects in the early embryo of the next generation. This will provide significant benefits, such as a new molecular understanding of heredity that could be key to thriving ....Extracellular vesicles in the inheritance of acquired traits. This project aims to examine the role of extracellular vesicles (EV) in the transfer of regulatory RNA from somatic cells to germline cells. This project suggests that somatic EVs from the epididymis transfer regulatory RNA to the sperm, and that this RNA exerts its effects in the early embryo of the next generation. This will provide significant benefits, such as a new molecular understanding of heredity that could be key to thriving in a changing environment.Read moreRead less
The nature and extent of mammalian transgenerational epigenetic inheritance. This project aims to understand how biological information can be passed from one generation to the next without being encoded in the genes. The results of this study will inform us how this can happen, and shed light on how often it happens in mammals.
Understanding the role of endogenous siRNAs in the maintenance of genomic defenses. The inappropriate expression of retrotransposons can cause increased genomic instability. The underlying molecular pathways that control retrotransposon expression are not known. This project proposes to investigate this question at a molecular level how naturally occurring small endogenous noncoding RNAs (endo-siRNAs) enforce the epigenetic silencing of retrotransposons and examine the likely impact of endo-siRN ....Understanding the role of endogenous siRNAs in the maintenance of genomic defenses. The inappropriate expression of retrotransposons can cause increased genomic instability. The underlying molecular pathways that control retrotransposon expression are not known. This project proposes to investigate this question at a molecular level how naturally occurring small endogenous noncoding RNAs (endo-siRNAs) enforce the epigenetic silencing of retrotransposons and examine the likely impact of endo-siRNAs expression in the packaging and maintenance of retrotransposons. Understanding this fundamental question will advance the scientific knowledge of small RNA functions in our genomic defense systems. Read moreRead less
Radical change in the architecture of a nucleus: loss of typical DNA organisation systems in dinoflagellates. The genetic blueprint of all higher cells is stored in the cell nucleus, and proteins called histones provide the filing system for compactly stacking and organising the cell's DNA. One group of organisms, the dinoflagellate algae, have lost this histone system. This project will provide insight into their alternative DNA management systems.
The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of pr ....The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of proteins (phasevarions) via variable methylation of the genome. The precise mechanism of action of these regulators is unknown. Characterisation of these systems will provide better understanding of bacterial gene regulation and adaptation, which will inform biotechnology and vaccine development and could contribute to economic and health advancements.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190101078
Funder
Australian Research Council
Funding Amount
$374,433.00
Summary
Functional role of a novel DNA modification in the adult brain. This project aims to understand how neuronal DNA is modified upon learning and how this impacts memory formation. The project will investigate the combination of different genome-wide sequencing approaches and molecular and cell biological assays to provide new insight into the functional role of a novel DNA modification, N6-methyl-2'-deoxyadenosine in the adult brain. This projects expects to have a major impact on many fields, inc ....Functional role of a novel DNA modification in the adult brain. This project aims to understand how neuronal DNA is modified upon learning and how this impacts memory formation. The project will investigate the combination of different genome-wide sequencing approaches and molecular and cell biological assays to provide new insight into the functional role of a novel DNA modification, N6-methyl-2'-deoxyadenosine in the adult brain. This projects expects to have a major impact on many fields, including neuroscience, evolutionary biology, and genetics, by helping to shape a new way of thinking about gene-environment interactionsRead moreRead less
Silencing the X chromosome: why and how. The project aims to understand why we have X chromosome inactivation, and examine the fundamental molecular mechanisms of how it is achieved. The project will explore RNA-mediated epigenetic modification of whole chromosomes with innovative molecular methods in placental mammals, and also iconic Australian mammals, to transform our understanding of X chromosome inactivation. Further understanding whole chromosome silencing, will inform future research int ....Silencing the X chromosome: why and how. The project aims to understand why we have X chromosome inactivation, and examine the fundamental molecular mechanisms of how it is achieved. The project will explore RNA-mediated epigenetic modification of whole chromosomes with innovative molecular methods in placental mammals, and also iconic Australian mammals, to transform our understanding of X chromosome inactivation. Further understanding whole chromosome silencing, will inform future research into potential therapies for chromosomal trisomies.Read moreRead less