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 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
Discovery Early Career Researcher Award - Grant ID: DE170100112
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Epitranscriptomic regulation of learning and memory. This project aims to investigate m6A, the most prevalent internal modification in eukaryotic messenger RNA, in the mammalian brain. The adult brain contains a high level of reversible m6A, suggesting that m6A regulates the neuronal transcriptome during synaptic plasticity, the cellular basis of learning and memory. This project will use epitranscriptomics to investigate the more than 100 modifications on RNA, many of which are not yet characte ....Epitranscriptomic regulation of learning and memory. This project aims to investigate m6A, the most prevalent internal modification in eukaryotic messenger RNA, in the mammalian brain. The adult brain contains a high level of reversible m6A, suggesting that m6A regulates the neuronal transcriptome during synaptic plasticity, the cellular basis of learning and memory. This project will use epitranscriptomics to investigate the more than 100 modifications on RNA, many of which are not yet characterised. Through molecular and mouse behavioural assays, the expected outcomes are insights into the post-transcriptional regulation underlying learning and memory, essential for survival in a constantly changing environment.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100976
Funder
Australian Research Council
Funding Amount
$307,058.00
Summary
Identifying parent-of-origin effects and their impact on complex traits. This project aims to systematically identify genetic variants whose effects depend on whether they were inherited from the mother or the father, and to assess their impact on complex human traits. Most gene mapping studies to date assume that the effects of genetic variants are equal regardless of the parent of origin, thus have not explored this source of genetic variation. However, animal studies indicate that parent-of-o ....Identifying parent-of-origin effects and their impact on complex traits. This project aims to systematically identify genetic variants whose effects depend on whether they were inherited from the mother or the father, and to assess their impact on complex human traits. Most gene mapping studies to date assume that the effects of genetic variants are equal regardless of the parent of origin, thus have not explored this source of genetic variation. However, animal studies indicate that parent-of-origin specific effects (POEs) are important contributors to variability of developmental and behavioural traits. Leveraging genetic and epigenetic data from some of the world’s largest cohorts, this project will improve our understanding of POEs on complex human traits related to early development, growth and behaviour.Read moreRead less
Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the ....Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
The importance of DNA methylation in response to environmental changes. This project aims to investigate the importance of DNA methylation, a process whereby gene expression can be altered without changes in the DNA code, in regulating our responses to environmental challenges. It plans to do so using well-validated models of adult exposure to high fat diet or psychological stress in mice and tissue-specific (liver and brain) deletion of the major methylation enzymes. It aims to compare function ....The importance of DNA methylation in response to environmental changes. This project aims to investigate the importance of DNA methylation, a process whereby gene expression can be altered without changes in the DNA code, in regulating our responses to environmental challenges. It plans to do so using well-validated models of adult exposure to high fat diet or psychological stress in mice and tissue-specific (liver and brain) deletion of the major methylation enzymes. It aims to compare functional, gene expression and methylation status after such challenges in intact and methylase deleted animals to determine how vital this process really is. This work has major implications for our understanding of epigenetics, and the ways in which genes interact with the environment especially in times of change.Read moreRead less
The role of RNA editing by the brain-specific enzym ADAR3 in learning and memory. Higher-order cognition sets us apart from other species but how this is achieved is still under debate. The project will test the idea, strongly supported by recent genomic analyses, that subtle changes in the sequences of RNA in response to environmental stimuli underpin this extraordinary ability.