HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility. This project is to define the biochemistry of a previously uncharacterized protein in male fertility using a unique mouse model and innovative DNA and protein technologies. This project will define a novel, and essential, pathway for male fertility and may ultimately have relevance to the maintenance of health or improving fertility.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775503
Funder
Australian Research Council
Funding Amount
$255,000.00
Summary
Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement p ....Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement programs such as are based at the Waite Campus. The outputs will include crops with increased tolerance to biotic and abiotic stresses, a reduced dependence on chemical inputs such as fertilisers and improved food quality, with consequent benefits to the environment and human health and nutrition.Read moreRead less
Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromoso ....Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromosomes at mitosis, meiosis and in sperm. I will use immunohistochemistry to clarify chromosome pairing and recombination at meiosis. This will answer some important general questions about chromosome behaviour and sex chromosome evolution.
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Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing seque ....Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing sequences and genes in microchromosomes of birds, reptiles and monotremes. This will clarify the origin and evolution of the ?microgenome?, establish its suitability as a model for vertebrate genome organisation, and demonstrate whether microchromosomes are the ancestors of the gene-rich regions of mammalian chromosomes.Read moreRead less
Regressive evolution of eyes in subterranean water beetles of arid-zone Australia: A comparative phylogenetic approach. Reduction or total loss of non-functional characters are common evolutionary phenomena, but little is known of the genetic basis of this regressive evolution. This project will use a phylogenetic framework to investigate the forces responsible for evolution of eyelessness in subterranean water beetles, by studying molecular genetic variation in three key eye developmental genes ....Regressive evolution of eyes in subterranean water beetles of arid-zone Australia: A comparative phylogenetic approach. Reduction or total loss of non-functional characters are common evolutionary phenomena, but little is known of the genetic basis of this regressive evolution. This project will use a phylogenetic framework to investigate the forces responsible for evolution of eyelessness in subterranean water beetles, by studying molecular genetic variation in three key eye developmental genes. The water beetles are explicitly suitable to address the questions due to their numerous independently evolved eyeless species and relatively old age of divergence from surface relatives. The research will provide a major new perspective on regressive evolution and the relationship between gene structure and function.Read moreRead less
Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control h ....Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control holistic physiological responses is largely unknown. By deciphering how neural networks are formed this project aims to provide broad biological insight to wiring of the entire nervous system which is likely to have significant implications for the formation of synthetic neural networks and for regeneration.Read moreRead less
Integrating a physical and functional genetic map of Prunus dulcis. Genome wide physical mapping is the centrepiece of current genomics research in virtually all plant and animal species. The proposal seeks to champion the development of Prunus dulcis (Rosaceae) as a model perennial species towards parity with other plant model systems for gene discovery and validation. The Rosaceae represents a rich repository of genes of relevance to perenniality, adaptation, sustainable agriculture, health a ....Integrating a physical and functional genetic map of Prunus dulcis. Genome wide physical mapping is the centrepiece of current genomics research in virtually all plant and animal species. The proposal seeks to champion the development of Prunus dulcis (Rosaceae) as a model perennial species towards parity with other plant model systems for gene discovery and validation. The Rosaceae represents a rich repository of genes of relevance to perenniality, adaptation, sustainable agriculture, health and nutrition and the bioindustries. Ultimately, comparative genomics across the family will advance molecular eco-genetics via dissection of traits determining adaptive response. Access to user-friendly molecular markers will also bring greater precision to breeding programmes. Read moreRead less
How common and what is the significance of cis-acting regulatory variation and genomic imprinting in plants? Plant based processes provide truly sustainable solutions to many of the challenges facing Australia. The proposed research will help elucidate how plants regulate variation in gene expression rather than changes in the structure of encoded proteins. This is an area of gene expression, that has not been approached before, that explains the plant's ability to respond to external stimuli. ....How common and what is the significance of cis-acting regulatory variation and genomic imprinting in plants? Plant based processes provide truly sustainable solutions to many of the challenges facing Australia. The proposed research will help elucidate how plants regulate variation in gene expression rather than changes in the structure of encoded proteins. This is an area of gene expression, that has not been approached before, that explains the plant's ability to respond to external stimuli. Variation between plant species in the number of genes does not fully explain the differences between them. This information will come not from seqenceing genomes but from investigation of regulatory elements. 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
Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 fun ....Genetic control of spermatogenesis: defining the role of SOX3 in spermatogonial progenitor cells. The transcription factor (TF) SOX3 is a key regulator of neural stem/progenitor cells. Recently, this project has also shown that SOX3 is active in sperm progenitors (spermatogonia) and is required for spermatogenesis. Using our Sox3 KO mouse model and extensive expertise in spermatogonial cell culture, ChIP-seq technology and bioinformatics, this project will investigate crucial aspects of SOX3 function in the testes including stem versus progenitor cell activity and genome-wide target gene regulation. These studies will uncover the molecular and cellular mechanism by which SOX3 controls spermatogenesis and provide unique insight into how a single TF controls context-dependent differentiation in sperm versus brain progenitor cells.Read moreRead less