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.
Leveraging Genomics Strategies To Generate Adult Neurons From IPSCs And Somatic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,593,336.00
Summary
Recent advances have made it possible to derive myriad specialized human cells from stem cells or by directly reprogramming cell identity. However, these derived cells are generally arrested at a fetal developmental stage, and do not mature to function like adult cells. We will use new genomic, epigenetic, cell reprogramming, and manipulation methods to discover how to derive mature cells, aiming to generate mature neurons for use in neurobiology research, disease modeling, and drug screening.
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
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
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
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
Discovery Early Career Researcher Award - Grant ID: DE150100460
Funder
Australian Research Council
Funding Amount
$380,000.00
Summary
Role of DNA methylation in response to low nutrient availability in plants. DNA methylation (mC) is a covalent modification of DNA essential for the establishment and maintenance of correct gene expression patterns and recently suggested to be responsive to some environmental cues in plants. Using cutting edge technologies, this project aims to identify nutrient stress-induced mC changes and investigate the role that these changes may play in transcriptional regulation, as well as assessing whet ....Role of DNA methylation in response to low nutrient availability in plants. DNA methylation (mC) is a covalent modification of DNA essential for the establishment and maintenance of correct gene expression patterns and recently suggested to be responsive to some environmental cues in plants. Using cutting edge technologies, this project aims to identify nutrient stress-induced mC changes and investigate the role that these changes may play in transcriptional regulation, as well as assessing whether these changes can be transmitted to the next generation to confer intergenerational stress responsiveness. Altogether this project aims to provide fundamental knowledge of the role of mC in plant gene regulation and stress response as well as paving the way for the next generation of novel crop-improvement strategies.Read moreRead less
Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how tem ....Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how temperature reverses chromosomal sex determination in dragon lizards. This could show how climatic extremes affect the biology of climate sensitive reptiles, and understand their vulnerability to climate change.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