The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
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Operator Integrals and Derivatives. The project is a contribution to the study of non-commutative differential and integral calculus. The novelty of the present project lies in the study of smoothness properties of functions whose domains and ranges are spaces of unbounded, non-commuting operators on some Hilbert space. Our general approach will be based on a detailed investigation of properties of double operator integrals, which permit smoothness estimates of operator-functions. It can be expe ....Operator Integrals and Derivatives. The project is a contribution to the study of non-commutative differential and integral calculus. The novelty of the present project lies in the study of smoothness properties of functions whose domains and ranges are spaces of unbounded, non-commuting operators on some Hilbert space. Our general approach will be based on a detailed investigation of properties of double operator integrals, which permit smoothness estimates of operator-functions. It can be expected that the new techniques generated will find further application in areas of mathematical physics and non-commutative geometry related to quantized calculus.
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Non-commutative analysis and differential calculus. This project is in an area of central mathematical importance and will lead to important scientific advances that will keep Australia at the forefront internationally in this field of research. There is an emphasis on international networking and we will collaborate with leading researchers in USA and France.
Development and regulation of thermogenesis in thermoregulating flowers. Flowers of certain primitive plants produce enough heat to raise their temperatures up to 40 C above the air, and regulate it at a nearly constant level. Like warm-blooded mammals, the flowers increase heat production as environmental temperature falls. However, they thermoregulate on a cellular level, unlike mammals with their complex nervous system. We aim to elucidate the mechanisms involved in regulation of heat-prod ....Development and regulation of thermogenesis in thermoregulating flowers. Flowers of certain primitive plants produce enough heat to raise their temperatures up to 40 C above the air, and regulate it at a nearly constant level. Like warm-blooded mammals, the flowers increase heat production as environmental temperature falls. However, they thermoregulate on a cellular level, unlike mammals with their complex nervous system. We aim to elucidate the mechanisms involved in regulation of heat-production, with molecular, biochemical and stable isotope techniques. We will investigate spatial and temporal patterns of gene expression and activity of putative regulatory enzymes. The results will have implications for human physiology and agriculture.Read moreRead less
Option pricing via path integrals: a new perspective. The risk management of derivative securities is a very exciting challenge for financial market researchers. The knowledge base resulting from this proposal will benefit both large financial institutions and Australia's financial system by creating a more competitive and efficient economic environment, which will inevitably lead to more gross domestic product (GDP) gains.Furthermore a large amount of software and numerical analysis work to be ....Option pricing via path integrals: a new perspective. The risk management of derivative securities is a very exciting challenge for financial market researchers. The knowledge base resulting from this proposal will benefit both large financial institutions and Australia's financial system by creating a more competitive and efficient economic environment, which will inevitably lead to more gross domestic product (GDP) gains.Furthermore a large amount of software and numerical analysis work to be developed during the project can be turned into IP for Australia. This will contribute to catalysing development of internationally competitive financial risk management software industry.Read moreRead less
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
Microgenomics - a tool to dissect effects of salinity on gene expression in specific cell types of Arabidopsis and rice. This project will provide novel, fundamental understanding of the cell type-specific processes involved in salinity tolerance in higher plants. As such, it will impact on our understanding of a range of processes relevant to salinity tolerance, an area of great importance to Australian agriculture and environmental sustainability. The increased understanding arising from this ....Microgenomics - a tool to dissect effects of salinity on gene expression in specific cell types of Arabidopsis and rice. This project will provide novel, fundamental understanding of the cell type-specific processes involved in salinity tolerance in higher plants. As such, it will impact on our understanding of a range of processes relevant to salinity tolerance, an area of great importance to Australian agriculture and environmental sustainability. The increased understanding arising from this project will underpin future work to increase agricultural productivity and the quality of life for all in the Australian and international communities.Read moreRead less
Calcium compartmentation in leaves: testing an integrated model of water and calcium transport with cell specific functional genomics. Calcium is a vital nutrient to animals and humans and its storage in vegetation is important for its accessibility. We believe this storage is linked to water flow in the leaf by a novel mechanism. This project will provide fundamental understanding of the cell type-specific processes involved in calcium storage and water flow in plants. High calibre PhD and Hono ....Calcium compartmentation in leaves: testing an integrated model of water and calcium transport with cell specific functional genomics. Calcium is a vital nutrient to animals and humans and its storage in vegetation is important for its accessibility. We believe this storage is linked to water flow in the leaf by a novel mechanism. This project will provide fundamental understanding of the cell type-specific processes involved in calcium storage and water flow in plants. High calibre PhD and Honours students will be educated to maintain the momentum of international excellence within Australia in the field of plant nutrient relations. The increase in understanding will allow future work to improve calcium availability and water use by plants to the benefit of agricultural productivity and quality of life.Read moreRead less
How IsomiRs Expand The MicroRNA Functional Repertoire In Affecting Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$439,570.00
Summary
MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA var ....MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA variation contributes to cancer.Read moreRead less