Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less
How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowl ....How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowled ....How does the chromatin remodeller CHD4 regulate gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are in many ways still mysterious. It is well established that gene expression patterns in complex organisms are determined in part by the manner in which DNA is physically packaged. Our aim is to define new aspects of these mechanisms that revolve around molecular motors that regulate DNA packaging. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
Uniting histone and transcription factor codes. This project aims to establish the general features of the “histone code”. It is well established that gene expression patterns are determined in part by the deposition, recognition and removal of post-translational modifications on the histone proteins that package eukaryotic DNA. This project proposes that this "histone code" is in fact a specific example of a transcription factor code. The project aims to enhance our understanding of the mechani ....Uniting histone and transcription factor codes. This project aims to establish the general features of the “histone code”. It is well established that gene expression patterns are determined in part by the deposition, recognition and removal of post-translational modifications on the histone proteins that package eukaryotic DNA. This project proposes that this "histone code" is in fact a specific example of a transcription factor code. The project aims to enhance our understanding of the mechanisms underlying gene regulation in plants and animals, and help to create improved strategies to optimise crop and farm animal properties and new-generation therapeutics.Read moreRead less
The Role of DNA Methylation in Transcription Factor Activity. Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by def ....The Role of DNA Methylation in Transcription Factor Activity. Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by defining the genome-wide set of sites and structural domains critical for binding. It also will explore the functional significance of these sequences using assays that investigate the importance of DNA methylation in KLF mediated cellular reprogramming to the pluripotent state.Read moreRead less
Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synth ....Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synthetic looping factors that can switch on a wide array of target genes. The project aims to answer fundamental questions about how proteins can establish and maintain physical loops in DNA to modulate gene expression. The project will also develop research tools that might ultimately correct diseases caused by the faulty expression of genes.Read 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
Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a mo ....Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a model for epigenetic change, and sex chromosomes, which has engaged some of the greatest genetic minds over nearly a century. Therefore my results will attract wide international interest and impact positively on Australia's scientific profile, and further highlight the importance of Australian mammals.Read moreRead less