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.
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
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.
Phenotypic profiling from DNA using genetic and epigenetic information. The project intends to quantify how much information about a person can be inferred from a DNA sample. A DNA sample contains epigenomic information additional to the genome sequence. This information can reflect age and the past and present lifestyle of the individual whose sample it is. The project aims to quantify the accuracy of lifestyle and phenotypic prediction from DNA. Existing genome-wide genotype and methylation ar ....Phenotypic profiling from DNA using genetic and epigenetic information. The project intends to quantify how much information about a person can be inferred from a DNA sample. A DNA sample contains epigenomic information additional to the genome sequence. This information can reflect age and the past and present lifestyle of the individual whose sample it is. The project aims to quantify the accuracy of lifestyle and phenotypic prediction from DNA. Existing genome-wide genotype and methylation array data from thousands of blood samples from human subjects will be statistically analysed to develop and validate predictors for chronological age, smoking, caffeine use, pesticide exposure, diet and body mass index. Potential applications of epigenomic prediction are widespread, ranging from forensics to ecology.Read moreRead less
Deciphering the genetic architecture of human complex traits. This project aims to develop statistical methods to integrate data from genetic studies of complex traits such as stature and cognition. Molecular phenotypes such as gene expression in large samples will be used to predict target genes and regulatory elements of those traits. Understanding the genetic basis of human complex traits is critical to longstanding questions in human and evolutionary biology. The project will also detect sig ....Deciphering the genetic architecture of human complex traits. This project aims to develop statistical methods to integrate data from genetic studies of complex traits such as stature and cognition. Molecular phenotypes such as gene expression in large samples will be used to predict target genes and regulatory elements of those traits. Understanding the genetic basis of human complex traits is critical to longstanding questions in human and evolutionary biology. The project will also detect signatures of natural selection in shaping the genetic variation in complex traits. The project will provide better understanding of complex traits in global populations and the history of human evolution, and will develop methods applicable in plant and animal contexts.Read moreRead less
The characterization of tiny Ribonucleic acids in animal epigenetics. Epigenetics, the inheritance of traits not encoded in deoxyribonucleic acid (DNA), is not well understood in animals. This project will investigate two classes of Ribonucleic acid (RNA) that may form part of an animal-specific epigenetic regulatory system. This study could revolutionize our understanding of animal genetics.
Discovery Early Career Researcher Award - Grant ID: DE120101916
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Characterisation of nuclear-localised microRNAs. This project is focused on a set of very small RNA molecules, called microRNAs that regulate genes activity. This project will likely redefine our understanding of microRNA-based gene regulation in complex animals, and may result in new RNA therapeutics for previously untreatable illnesses.