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 .
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.
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
Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC is ....Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC isoforms with desirable properties. Ultimately, the project aims to identify isoforms that improve plant fitness under stress conditions. Optimising PEPC activity will provide next generation solutions to improve water balance and carbon assimilation to keep C4 crops productive under future climates.Read moreRead less
A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough ....A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough and responsive hydrogel platform from this disordered protein family through greater understanding of structure and mechanical function and incorporating adequate stiffness, strength and biocompatibility. Such tough hydrogels would be applicable to a range of biotechnological applications (eg intervertebral disc repair or artificial skin tissue engineering).Read moreRead less
Industrial Transformation Research Hubs - Grant ID: IH220100017
Funder
Australian Research Council
Funding Amount
$4,808,669.00
Summary
ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The progra ....ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The program addresses industry-led challenges for translation of biologics as molecular radiopharmaceuticals, building capacity in biomanufacturing, radiobiology and radiochemistry. The program establishes a dedicated manufacturing pipeline, future-proofing production and securing supply chain of next generation medical technologies.Read moreRead less
Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors w ....Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors will be used to devise a simple portable colorimetric test that can be performed in the vineyard or the winery. The ability to rapidly determine the level of grape contamination with phenolic glucosides would give Australian wine growers and wine makers a powerful tool to mitigate the effects of bushfires.Read moreRead less
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100190
Funder
Australian Research Council
Funding Amount
$620,000.00
Summary
Electrophysiology Platform for Ion-channel Characterisation. Ion channels are ubiquitous pore-forming membrane proteins, with the human genome encoding >300 ion channels. The diverse roles of ion channels include action potential generation, control of ion flow across secretory and epithelial cells, and regulation of cell volume, motility and proliferation. Pharmacological modulators are powerful tools for probing ion channel function, but for most channels these tools are lacking. Thus, this p .... Electrophysiology Platform for Ion-channel Characterisation. Ion channels are ubiquitous pore-forming membrane proteins, with the human genome encoding >300 ion channels. The diverse roles of ion channels include action potential generation, control of ion flow across secretory and epithelial cells, and regulation of cell volume, motility and proliferation. Pharmacological modulators are powerful tools for probing ion channel function, but for most channels these tools are lacking. Thus, this project aims to develop the first comprehensive toolbox of ion channel modulators using an integrated in vitro/in vivo electrophysiology platform. These pharmacological tools will be made freely available to the Australian research community for probing the mechanism and physiological function of ion channels.Read moreRead less