Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant be ....Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant benefits, such as to the economy by offering a cost-effective alternative to sequencing methods currently used to map DNA and RNA modifications.Read moreRead less
Next-generation epigenetic analysis: direct reading of DNA methylation. This project aims to develop a new molecular tool to directly and dynamically read chemical modifications on genomic DNA (epigenetics) by utilizing advanced nanomaterials with the unique features of Raman spectroscopy. Epigenetics affects cellular processes and controls genetic programs by turning them “on” and “off" but there is currently no direct method to measure modifications on DNA. A new technology will be designed to ....Next-generation epigenetic analysis: direct reading of DNA methylation. This project aims to develop a new molecular tool to directly and dynamically read chemical modifications on genomic DNA (epigenetics) by utilizing advanced nanomaterials with the unique features of Raman spectroscopy. Epigenetics affects cellular processes and controls genetic programs by turning them “on” and “off" but there is currently no direct method to measure modifications on DNA. A new technology will be designed to avoid complicated procedures/chemistry for DNA epigenetic analysis providing a specific molecular fingerprint. The anticipated outcomes include a new technique and advanced knowledge in nanomaterials and DNA functions, thus strengthening the economic viability of Australian manufacturing and biotechnology sectors.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
Discovery Early Career Researcher Award - Grant ID: DE180100219
Funder
Australian Research Council
Funding Amount
$343,551.00
Summary
Molecular mechanism for the regulation of Polycomb repressive complex 2. This project aims to determine how the histone methyltransferase Polycomb repressive complex 2 (PRC2) is regulated. The project expects to generate new knowledge in transcription regulation and epigenetics. The intended outcome is to enhance the national capabilities in two important fields, Polycomb biology and cryo-electron microscopy (cryo-EM). This should provide significant benefits, including strengthening of the epig ....Molecular mechanism for the regulation of Polycomb repressive complex 2. This project aims to determine how the histone methyltransferase Polycomb repressive complex 2 (PRC2) is regulated. The project expects to generate new knowledge in transcription regulation and epigenetics. The intended outcome is to enhance the national capabilities in two important fields, Polycomb biology and cryo-electron microscopy (cryo-EM). This should provide significant benefits, including strengthening of the epigenetic community through the development of innovative research program in Polycomb biology and the establishment of a national world-class cryo-EM community.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101669
Funder
Australian Research Council
Funding Amount
$430,485.00
Summary
Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes . This project aims to address the fundamental question of how genes are switched off by studying a group of molecular off-switches, the polycomb group proteins. The project is expected to generate new knowledge in the area of gene regulation and epigenetics by combining innovative methods of structural biology and cell biology in an interdisciplinary way. The expected outcomes include a more complete picture of the molecu ....Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes . This project aims to address the fundamental question of how genes are switched off by studying a group of molecular off-switches, the polycomb group proteins. The project is expected to generate new knowledge in the area of gene regulation and epigenetics by combining innovative methods of structural biology and cell biology in an interdisciplinary way. The expected outcomes include a more complete picture of the molecular mechanisms that regulate gene expression and the development of novel methods to image the genome. This should provide significant benefits, such as facilitated development of gene editing tools and regulatory circuits for synthetic biology, as well as novel capabilities to image the genome at high resolution Read moreRead less
DNA exhibits new self-assembled structures due to clustered DNA methylation. This project aims to develop a technology to investigate detailed epigenetic patterns in DNA by directly interrogating the physical properties of DNA polymers in their native state. Epigenetics controls whether genes and genetic programs are turned on or off in living systems. The project will build on a recent discovery that key physical properties of native DNA polymers are strongly influenced by epigenetic patterns c ....DNA exhibits new self-assembled structures due to clustered DNA methylation. This project aims to develop a technology to investigate detailed epigenetic patterns in DNA by directly interrogating the physical properties of DNA polymers in their native state. Epigenetics controls whether genes and genetic programs are turned on or off in living systems. The project will build on a recent discovery that key physical properties of native DNA polymers are strongly influenced by epigenetic patterns created by living organisms. By fully understanding this phenomenon, this project aims to provide new tools for the study of epigenetics with broad potential applications in the life sciences, biotechnology and nanotechnology.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
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
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