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Engineering improved and multifunctional gene editing systems. Advances in genome editing have enabled the targeted modulation of gene expression in cells and provided new tools for biotechnology. This project will combine computational design and genetic selection to deliver the next generation of precision gene editing tools. These new technologies can be used for modification of genes in any cellular compartment and will be useful for understanding and improving energy metabolism. Increased c ....Engineering improved and multifunctional gene editing systems. Advances in genome editing have enabled the targeted modulation of gene expression in cells and provided new tools for biotechnology. This project will combine computational design and genetic selection to deliver the next generation of precision gene editing tools. These new technologies can be used for modification of genes in any cellular compartment and will be useful for understanding and improving energy metabolism. Increased cellular energy production can be harnessed to make valuable biological products, with unprecedented efficiency.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101962
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Functional epigenomics interrogation of DNA methylation dynamics during vertebrate development and evolution. DNA methylation (mC) is an epigenetic signal essential for the maintenance of correct gene expression patterns. To investigate the causal relationships between mC and transcription during vertebrate embryonic development and evolution, this project will perform high-resolution mC profiling at different stages of teleost, amphibian and mammalian development. Highly conserved and syntenic, ....Functional epigenomics interrogation of DNA methylation dynamics during vertebrate development and evolution. DNA methylation (mC) is an epigenetic signal essential for the maintenance of correct gene expression patterns. To investigate the causal relationships between mC and transcription during vertebrate embryonic development and evolution, this project will perform high-resolution mC profiling at different stages of teleost, amphibian and mammalian development. Highly conserved and syntenic, methylated sequences will then be used as baits in proteomics screens to identify novel 5mC 'readers'. The generation of genomic profiles of mC 'readers' and their integration with developmental mC maps will reveal transient epigenome dynamics during vertebrate embryogenesis and provide new insights into the conservation of these crucial developmental mechanisms.Read moreRead less
Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling ca ....The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling causal genetic variation. The unique cell markers and regulatory networks will be validated with tissue specific and transgenic tools that can work across a host of plant species to reveal adaptive cellular responses to harsh environmental conditions.Read moreRead less
Unique epigenetic states in plant stem cell niches for safeguarding genome integrity. Plant stem cells are the foundation cells of all plant growth and development, including generation of the reproductive cells. Therefore, it is critical that stem cells defend against attacks that may damage the genome. A unique epigenetic state in plant stem cell niches has been discovered that may protect the genome from damage due to parasitic DNA elements. Using sophisticated genomics, genetics, and cellula ....Unique epigenetic states in plant stem cell niches for safeguarding genome integrity. Plant stem cells are the foundation cells of all plant growth and development, including generation of the reproductive cells. Therefore, it is critical that stem cells defend against attacks that may damage the genome. A unique epigenetic state in plant stem cell niches has been discovered that may protect the genome from damage due to parasitic DNA elements. Using sophisticated genomics, genetics, and cellular technologies, this project will investigate how stem cell epigenetic state is linked to genome defence, how environmental stresses can disrupt the defence system, and the role of the system in driving new genetic diversity. This knowledge is of high importance as agricultural crops enter an era of increasingly challenging conditions.Read moreRead less
Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itse ....Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itself. This project expects to unravel the functional contributions of DNA methylation to vertebrate embryogenesis by using latest cutting-edge genomics techniques. The project will be carried out on the highly tractable zebrafish model system which allows for easy genetic manipulation of the desired sequences. This project aims to provide a better understanding of embryonic development of vertebrates, including humans.Read moreRead less