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
Why do only some exotics become invasive? Combining ecological and genomic approaches to address alternative hypotheses in a recent Australian weed. This project will specifically test alternative hypotheses about how weeds become invasive. As invasive weeds affect both agricultural and native ecosystems equally, research on understanding the mechanisms of weed invasion is critical. Outcomes will benefit Australia by allowing better prioritisation of management against exotic plants already i ....Why do only some exotics become invasive? Combining ecological and genomic approaches to address alternative hypotheses in a recent Australian weed. This project will specifically test alternative hypotheses about how weeds become invasive. As invasive weeds affect both agricultural and native ecosystems equally, research on understanding the mechanisms of weed invasion is critical. Outcomes will benefit Australia by allowing better prioritisation of management against exotic plants already in the country by providing predictive tools to estimate likelihood of spread. For formal Pest Risk Analysis by regulators (eg Biosecurity Australia), our project will provide genomic tools by which the potential weediness of a regulated plant can be assessed through genetic screening, and forms part of an international effort to identify 'weedy genes'. Read moreRead less
Tree-mediated methane fluxes: A new frontier in the global carbon cycle. Methane is an extremely potent greenhouse gas. Recent evidence suggests that tree-mediated fluxes may be a significant, but overlooked source of methane to the atmosphere. This project aims to quantify the magnitude and drivers of tree-mediated methane fluxes from Australia’s dominant forest types. Innovatively, we will be using a novel combination of empirical field based measurements, gas tracer experiments, microbial ana ....Tree-mediated methane fluxes: A new frontier in the global carbon cycle. Methane is an extremely potent greenhouse gas. Recent evidence suggests that tree-mediated fluxes may be a significant, but overlooked source of methane to the atmosphere. This project aims to quantify the magnitude and drivers of tree-mediated methane fluxes from Australia’s dominant forest types. Innovatively, we will be using a novel combination of empirical field based measurements, gas tracer experiments, microbial analysis and modelling methods. Expected outcomes are a mechanistic understanding of tree-mediated methane fluxes, helping to constrain regional, national and global methane budgets. The results of this study will help inform publicly funded greenhouse gas abatement strategies, ensuring a maximal return on investment.Read moreRead less
The effect of aerial spraying of two pesticides on semi-arid grasslands. The project will investigate how two pesticides, fipronil and metarrhizium, used to control locusts, affect semi-arid ecosystems by examining impacts on invertebrates, their predators, lizards and soil processes. The effects will be followed through time in a large scale experiment to determine recovery and compare each pesticide.
Testing our knowledge on the dawn of animal life: evidence from the fossil record against modern ecological and morphological analogues. The Cambrian 'Explosion', half a billion years ago, is regarded as one of the most important events in the history of the Earth, when most major animal groups first appear in the rock record, and for which South Australia has recently become a significant source of spectacular fossils. However, important questions remain regarding their Ediacaran roots, the spe ....Testing our knowledge on the dawn of animal life: evidence from the fossil record against modern ecological and morphological analogues. The Cambrian 'Explosion', half a billion years ago, is regarded as one of the most important events in the history of the Earth, when most major animal groups first appear in the rock record, and for which South Australia has recently become a significant source of spectacular fossils. However, important questions remain regarding their Ediacaran roots, the speed of evolution at the time, and the environments in which the radiation took place. Studying the fossil evidence in the light of present-day ecological frameworks, and in comparison with modern behavioural and morphological analogues, as well as living relatives, can help us better assess our understanding of this first radiation of animals.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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A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
Mechanisms Of Premature Cranial Fusion: Role Of Retinol Binding Protein 4 In Osteogenesis And Suture Fusion
Funder
National Health and Medical Research Council
Funding Amount
$555,855.00
Summary
Craniosynostosis is a condition where the skull bones fuse prematurely, affecting skull shape, vision and cognition. It occurs in 1 in 2,500 births. The only treatment is surgery, which is life-threatening, costly and may need to be repeated. By studying how fusion happens in this project we may be able to devise therapies to minimize the risks and need for re-operation. Here, we hope to show that modification of a single substance in the skull of mouse models can prevent premature bone fusion.
The Role Of Arousal And Diaphragm Displacement In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$410,875.00
Summary
Obstructive sleep apnea (OSA) affects 4% of men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease e.g. heart attacks and strokes. OSA is characterized by repetitive obstructions of the floppy portion of the throat during sleep with adverse effects on oxygen levels and sleep quality. OSA is strongly associated with obesity and is 2-3 times more common in men than women. How obesity and male gender predispose to OSA is ....Obstructive sleep apnea (OSA) affects 4% of men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease e.g. heart attacks and strokes. OSA is characterized by repetitive obstructions of the floppy portion of the throat during sleep with adverse effects on oxygen levels and sleep quality. OSA is strongly associated with obesity and is 2-3 times more common in men than women. How obesity and male gender predispose to OSA is not known. We will investigate two factors that we believe are most likely involved in causing and explaining this gender difference in OSA. We will examine if breathing responses with brief awakening are sufficient to promote OSA patterns of breathing in snorers and if they are greater in male than female OSA patients. We have already shown that healthy men have greater breathing response to arousal compared to women. These brief arousals occur hundreds of times a night in OSA patients, and over-breathing on arousal may increase the probability of upper airway obstruction on falling back to sleep. We will also investigate why even healthy men show greater breathing responses compared to women. Men tend to accumulate fat centrally, particularly in the abdomen, whereas in women fat tends to be distributed more to the hips and thighs. This could be very important in OSA because downward pull exerted on the upper airway by the diaphragm is likely to be reduced in people with more abdominal obesity. This mechanisms has not yet been studied in humans. We will therefore investigate if increased forces placed on the diaphragm during sleep make the upper airway more prone to collapse. We will also investigate these effects during sleep onset, when there may well be important changes in diaphragm position as muscles relax.Read moreRead less
Control points in nitrogen uptake: enhancing the response of cereals to nitrogen supply and demand. Vast amounts of nitrogen fertiliser are applied to cereal crops to maintain yields. By uncovering what limits nitrogen uptake in cereals, this project will provide the scientific basis for improving nitrogen use efficiency and decreasing fertiliser use, with significant economic and environmental benefits.