Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.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
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less
The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its ....The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its phenotype. By studying the effects of Cyp genes on fly survival, Cyp gene expression and regulation, and expressing selected Cyp genes in a yeast expression system, we will enhance our understanding of Cyp gene function and evolution.Read moreRead less
A New Window into Transgene Silencing in Plants: mechanisms of copy-number independent, 5' sequence dependent, post-transcriptional silencing in a complex polyploid. Silencing of introduced genes is a major problem limiting plant molecular improvement. Sugarcane, a complex polyploid, shows the most efficient transgene silencing ever observed in plants. Silencing operates on the RNA, depends on the upstream sequence of the gene, and is independent of copy number. Other plant species develop endop ....A New Window into Transgene Silencing in Plants: mechanisms of copy-number independent, 5' sequence dependent, post-transcriptional silencing in a complex polyploid. Silencing of introduced genes is a major problem limiting plant molecular improvement. Sugarcane, a complex polyploid, shows the most efficient transgene silencing ever observed in plants. Silencing operates on the RNA, depends on the upstream sequence of the gene, and is independent of copy number. Other plant species develop endopolyploidy with age, and show unpredictable or patchy silencing. We speculate that differential silencing is a natural control mechanism in the exploitation of polyploidy in plants. The sugarcane system provides an exceptional opportunity to identify the sequences that trigger and protect from silencing, and to develop approaches to avoid the problem.Read moreRead less
Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to ident ....Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to identify candidates for a wide variety of these proteins. The aim of this project is to establish systems in which the functional properties of these transporter proteins may be characterised in detail.Read moreRead less
Plant transformation: exploiting anti-apoptosis genes for very high efficiency transformation. Crop improvement through genetic modification depends on the ability to transform target species. The most desirable method is Agrobacterium mediated transformation. However, plant species and cultivars differ significantly in their ability to be efficiently transformed by Agrobacterium. This is particularly true for the economically important cereals. We have discovered that anti-apoptosis genes, whic ....Plant transformation: exploiting anti-apoptosis genes for very high efficiency transformation. Crop improvement through genetic modification depends on the ability to transform target species. The most desirable method is Agrobacterium mediated transformation. However, plant species and cultivars differ significantly in their ability to be efficiently transformed by Agrobacterium. This is particularly true for the economically important cereals. We have discovered that anti-apoptosis genes, which inhibit programmed cell death, dramatically increase the Agrobacterium transformation efficiency in bananas and sugarcane. We will utilise this information and develop the use of these genes to increase the efficiency of transformation in those crops and cultivars that are difficult to transform using Agrobacterium.Read moreRead less
Discovery of novel microRNA biogenesis and functional components. Discovery of novel microRNA components will provide new strategies for confronting a diverse array of challenges Australia faces, such as the increasing rates of certain cancers in our population, to stresses on our crop plants faced with environmental changes. The biological mechanisms underlying these disparate problems are unified by microRNA involvement in many instances. By finding microRNA controlling factors common to all h ....Discovery of novel microRNA biogenesis and functional components. Discovery of novel microRNA components will provide new strategies for confronting a diverse array of challenges Australia faces, such as the increasing rates of certain cancers in our population, to stresses on our crop plants faced with environmental changes. The biological mechanisms underlying these disparate problems are unified by microRNA involvement in many instances. By finding microRNA controlling factors common to all higher organisms, we expect our community will benefit from the increased knowledge base that will help our researchers adopt new strategies in fighting diseases and improving our agricultural industry.Read moreRead less
Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is ....Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is to elucidate how genes are assembled into complex active or inactive chromatin structures by employing a novel in vitro system. This information will have important implications for gene therapy strategies.
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The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This s ....The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This study will uncover the underpinning mechanism of how our chromosomes are organised into distinct functional domains, which may offer the potential to develop new strategies to correct chromosomal abnormalities.
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