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Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.
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
Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, thro ....Feeding and digestion in tropical rock lobster phyllosoma larvae and its applications for culture. Provision of larval culture diets that provide optimal nutrition in a suitable presentation format is the major challenge for developing a rock lobster aquaculture industry. Tropical rock lobsters are likely contenders due to their faster growth rates and shorter larval phase than temperate species. This project will assess the ingestive and digestive capabilities of larvae during development, through an examination of mouthpart and gut structure and their types and concentration of digestive enzymes. Information will be used to formulate and test improved diets of appropriate size, texture and nutritional composition and will be the first comprehensive analysis of preferred larval diets on the basis of their biological and physiological characteristics.Read moreRead less
Integrated System Wide Characterization Of Microbiota And Host Factors Influencing Intestinal Colonization Resistance To The Healthcare Pathogen Clostridium Difficile
Funder
National Health and Medical Research Council
Funding Amount
$359,999.00
Summary
Naturally occurring bacteria play an important role in determining patient disease susceptibility, disease progression and ultimately, disease outcome. Over 1000 species of bacteria, contributing 10 times as many cells as found within a single individual. This project seeks to understand these communities, how they confer resistance to infection and how they can be manipulated, both naturally and through controlled introduction of bacteria to prevent disease or improve disease outcome.
Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, ....Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, for example in disease such as diabetes or transplant rejection. Furthermore, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the ....Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the host's immune system will also be gained. The techniques established during the study of MSP-2 will be useful for the study of larger proteins and protein complexes from many systems in the future.Read moreRead less