Meiotic recombination in Neurospora crassa: a model for the process in humans and other multicellular eukaryotes. Genes are shuffled by recombination during meiosis in the sexual cycle of higher organisms. This is best understood in yeast. Our findings show Neurospora recombination differs from yeast recombination. It is more tolerant of sequence mismatch, differs in the relative frequencies of gene conversion and crossing over, has frequently interrupted conversion tracts and has transacting ge ....Meiotic recombination in Neurospora crassa: a model for the process in humans and other multicellular eukaryotes. Genes are shuffled by recombination during meiosis in the sexual cycle of higher organisms. This is best understood in yeast. Our findings show Neurospora recombination differs from yeast recombination. It is more tolerant of sequence mismatch, differs in the relative frequencies of gene conversion and crossing over, has frequently interrupted conversion tracts and has transacting genes controlling recombination hotspot activity. We propose to genetically dissect Neurospora recombination which appears to be a closer model for recombination in humans and other higher eukaryotes, where understanding recombination can assist control of genetic disease, efficient breeding in agriculture and our understanding of evolution.Read moreRead less
Developmental regulation of plant mitochondrial genome structure and copy number. Recombination is a major driving force behind mitochondrial DNA evolution and is responsible for the occurrence of cytoplasmic male sterile plants that are used by plant breeders to obtain high yield hybrids. A better understanding of the mechanisms that underlie mitochondrial and chloroplast genome maintenance and segregation will be a major fundamental scientific advance that will permit an integrated picture of ....Developmental regulation of plant mitochondrial genome structure and copy number. Recombination is a major driving force behind mitochondrial DNA evolution and is responsible for the occurrence of cytoplasmic male sterile plants that are used by plant breeders to obtain high yield hybrids. A better understanding of the mechanisms that underlie mitochondrial and chloroplast genome maintenance and segregation will be a major fundamental scientific advance that will permit an integrated picture of the interactions between the three plant genomes (nuclear, mitochondrial and chloroplastic). It is also a pre-requisite for the future manipulation of the cytoplasmic genomes leading to new ways to develop varieties with modified cytoplasms.Read moreRead less
Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a fra ....Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a framework to test regulatory network models and to analyse the molecular basis of interactions between control systems. This research will eventually provide the ability to predict how cells respond to drugs and other environmental stimuli.Read moreRead less
A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We hav ....A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We have shown that Neurospora, like other less tractable multicellular eukaryotes, is tolerant of sequence mismatch, allowing high resolution analysis of individual recombination events. This project will build on fundamental advances we have already made in understanding how recombination occurs.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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How sexually antagonistic genes and sexual selection influence the evolution of the Y chromosome. Sexually antagonistic genes are beneficial to members of one sex, but costly to the other. They are of significance both to the coevolution between the sexes and the evolution of the sex chromosomes. We will measure the sexually antagonistic effects of genes that make male guppies sexually attractive. We will then study how these genes, and the process of sexual selection that favours them influence ....How sexually antagonistic genes and sexual selection influence the evolution of the Y chromosome. Sexually antagonistic genes are beneficial to members of one sex, but costly to the other. They are of significance both to the coevolution between the sexes and the evolution of the sex chromosomes. We will measure the sexually antagonistic effects of genes that make male guppies sexually attractive. We will then study how these genes, and the process of sexual selection that favours them influence the process of recombination between the X and Y chromosomes.Read moreRead less
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
Evolutionary genetics of bovid genomes over 60,000 years. This project will provide data critical for understanding the genetic background of modern cattle and bison, and how humans have shaped factors such as milk yield, growth rates and muscle mass. It will also reveal genes and genomic regions that were favoured in the domestication process, including those potentially linked to genes of commercial interest for future research. This pioneering ancient DNA approach will also be applicable to a ....Evolutionary genetics of bovid genomes over 60,000 years. This project will provide data critical for understanding the genetic background of modern cattle and bison, and how humans have shaped factors such as milk yield, growth rates and muscle mass. It will also reveal genes and genomic regions that were favoured in the domestication process, including those potentially linked to genes of commercial interest for future research. This pioneering ancient DNA approach will also be applicable to a variety of other domestic crops and animals. The unique temporal analysis of microevolution will provide crucial data for genetic research, and groundproof our attempts to analyse the timing and nature of human evolutionary history, major domestication events and inform conservation management.Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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