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
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: De140101962
Funder
Australian Research Council
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
System-level characterisation of the siphonophore, Indo-Pacific man o' war. The Indo-Pacific man o' war (bluebottle), is a cnidarian from the siphonophore order. These animals frequent Australian beaches in swarms and cause thousands of stings every year. The project proposes to profile the genome, transcriptome, epigenome, and proteome of the bluebottle to gain insight into its life cycle, its behaviour, and toxins. Expected outcomes include the generation of novel information related to bluebo ....System-level characterisation of the siphonophore, Indo-Pacific man o' war. The Indo-Pacific man o' war (bluebottle), is a cnidarian from the siphonophore order. These animals frequent Australian beaches in swarms and cause thousands of stings every year. The project proposes to profile the genome, transcriptome, epigenome, and proteome of the bluebottle to gain insight into its life cycle, its behaviour, and toxins. Expected outcomes include the generation of novel information related to bluebottle gene regulation and its toxin repertoire, which will be highly beneficial for the design of future sting treatment strategies. Given that the bluebottle is a colony made of functionally specialised polyps, this study will also provide significant novel insight into the origins and evolution of animal multicellularity.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
Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
Towards genome methylation based crop improvement. Deoxyribonucleic acid (DNA) methylation is a form of genetic control that regulates crop performance and the crop's response to the environment. Improving understanding of the inheritance of methylation in relation to crop performance will provide the basis for methylation based breeding for climate resilient crops.
Deciphering the regulation and function of the epigenome in eukaryotic development and stress response. The epigenome is an additional regulatory code superimposed upon plant and animal genomes that controls how they operate. This project will aim to understand the information encoded in the epigenome and how it changes in development and environmental stress, enabling manipulation of its function in crops and correction of its dysfunction in disease.
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