Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and dete ....Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and determine the architecture of several chromatin states with unique functional implications inside the cell. This will unravel the molecular instructions that define how our genomes are organised, significantly advancing our knowledge of fundamental eukaryotic genome biology and paving the way for the future development of new tools and therapies.Read moreRead less
Tracking factor footprints to reveal the intricacy and control of translation initiation. Messenger ribonucleic acid (RNA) translation is required for all of life and knowledge of how it works is central to modern life sciences. This project will develop novel ways of studying translation, generating entirely new descriptions of its inner workings that may transform knowledge of gene function and its use in medical and biotechnological processes.
Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this pro ....Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this project aims to combine anthropological genetics with cutting-edge functional genomics in a pioneer multidisciplinary approach. Ultimately, this project may transform our understanding of both the population and evolutionary pressures that have acted upon these groups in the past 50,000 years.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Understanding disease resistance gene evolution across the Brassicaceae. Pan genomes represent the diversity of a species, including structural and sequence variation, which cannot be provided by a reference genome alone. In this project we will characterise resistance gene diversity across the Brassicaceae pan genomes. Through comparison with resistance gene diversity in cultivated Brassica species we will understand selection underlying resistance gene evolution in wild species and subsequent ....Understanding disease resistance gene evolution across the Brassicaceae. Pan genomes represent the diversity of a species, including structural and sequence variation, which cannot be provided by a reference genome alone. In this project we will characterise resistance gene diversity across the Brassicaceae pan genomes. Through comparison with resistance gene diversity in cultivated Brassica species we will understand selection underlying resistance gene evolution in wild species and subsequent domestication and breeding. Knowledge on how variation affects disease susceptibility, especially to the devastating fungal pathogen blackleg, and contributes to phenotypic variation, will lead to improved plant protection strategies and increased crop resilience.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
Road rules for traffic on DNA - gene regulation by encounters between transcribing RNA polymerases and DNA-bound proteins. This project addresses a widespread but poorly understood phenomenon in gene regulation. The work will support Australian industries by supplying new tools for manipulation of gene expression for industrial and medical applications and will provide unique opportunities for Australian students in this emerging field.
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
Discovery Early Career Researcher Award - Grant ID: DE160100755
Funder
Australian Research Council
Funding Amount
$371,000.00
Summary
Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. Th ....Evolution of genome architecture. The project aims to understand how changes to genome architecture over evolutionary time are linked to the diversity of animal morphology. Our genome sequence is arranged into higher order structures that enable coordinated gene expression. The appropriate expression of genes in time and space is necessary to produce the multitude of cell types that make up a multicellular organism. Yet, to date, genome topology is poorly explored, especially between species. The project involves comparisons of the 3D structure of genomes in divergent species. These findings are expected to inform the underlying principles of gene regulation in animals and species evolution.Read moreRead less