Mechanisms Of Nedd4/Nedd4-2-mediated Regulation Of The Epithelial Sodium Channel
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
The epithelial sodium channel (ENaC) is a highly specific ion channel expressed in the apical membrane of some tissues. In the kidney, ENaC activity is responsible for maintaining sodium balance, blood volume and blood pressure. In the lung ENaC function is required for fluid clearance. Abnormal regulation of ENaC is associated with conditions such as hypertension, cystic fibrosis and pulmonary oedema. Delineating the molecular basis of the regulation of ENaC is vital in understanding disease me ....The epithelial sodium channel (ENaC) is a highly specific ion channel expressed in the apical membrane of some tissues. In the kidney, ENaC activity is responsible for maintaining sodium balance, blood volume and blood pressure. In the lung ENaC function is required for fluid clearance. Abnormal regulation of ENaC is associated with conditions such as hypertension, cystic fibrosis and pulmonary oedema. Delineating the molecular basis of the regulation of ENaC is vital in understanding disease mechanisms and in defining targets for novel therapeutics for the treatment of disorders that arise due to sodium imbalance. Furthermore, ENaC and the molecules involved in the channel regulatory cascade are potential candidate genes in defining the genetic causes of human hypertension and salt wasting disorders. Previous studies from our laboratories and by other groups have shown that Nedd4 and Nedd4-2 proteins are key players in regulating ENaC activity. Our recent NHMRC supported work has identified another important protein, Grk2, as a regulator of ENaC. The work proposed in this application is an extension of our recent findings and will enable us to fully define how Nedd4-Nedd4-2 and Grk2 regulate the activity of ENaC.Read moreRead less
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883081
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
High Content Cell Signaling Discovery and Screening Facility. The national benefits of this facility will be an increase in basic knowledge of how cells transmit signals to determine their behaviour in normal or stressed situations. There will be high impact publications in learned journals, new IP developed, enhanced education and training in cutting edge technologies. The discoveries from this work will provide candidates for development by the Biotechnology industry in Australia. All of this ....High Content Cell Signaling Discovery and Screening Facility. The national benefits of this facility will be an increase in basic knowledge of how cells transmit signals to determine their behaviour in normal or stressed situations. There will be high impact publications in learned journals, new IP developed, enhanced education and training in cutting edge technologies. The discoveries from this work will provide candidates for development by the Biotechnology industry in Australia. All of this will promote an innovation culture and economy. The work done in this facility addresses several National Research Priority areas including Promoting and maintaining good health, Frontier technologies for transforming industry and Safeguarding Australia.Read moreRead less
Identifying novel insecticides and their targets: probing Australian arachnid venoms. Insect pests destroy an estimated 2-3 billion dollars of crops in Australia. Insect pests also are responsible for the transmission of many new and re-emerging human, animal and plant diseases threatening health, wellbeing and prosperity. Current insecticides are severely limited by toxicity and/or insect resistance, and some are undergoing use cancellation overseas. Thus there is an urgent need to develop safe ....Identifying novel insecticides and their targets: probing Australian arachnid venoms. Insect pests destroy an estimated 2-3 billion dollars of crops in Australia. Insect pests also are responsible for the transmission of many new and re-emerging human, animal and plant diseases threatening health, wellbeing and prosperity. Current insecticides are severely limited by toxicity and/or insect resistance, and some are undergoing use cancellation overseas. Thus there is an urgent need to develop safer and more specific insecticides that are effective against disease vectors and agricultural pest insects, as well as to identify new insecticide targets. This research has a multi-million dollar potential benefit to agricultural, health and pest control sectorsRead moreRead less
Regulation Of Pre-mRNA And MRNA Processing By The Neuron-specific Hu RNA-binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$477,750.00
Summary
The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, t ....The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism's homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating the activation of individual genes as they are copied from DNA to RNA. However, this activation is just the start of the process to produce an active protein. In higher organisms, these RNA copies almost always contain interruptions called introns, which must be excised from the RNA. Also, protein factors bound to specific RNAs can dictate whether the RNA is used to make protein or not, and these factors can also affect the localisation of the RNA to a specific sub-cellular destination, giving rise to highly localised protein expression. Evidence suggests that neurons are a cell type that rely heavily on mechanisms of RNA regulation. During development neurons become highly polarised, acquiring an axon which can elongate and find distant synaptic targets. While much is known about how axon growth cones respond to various guidance cues, the mechanisms by which the axon is able to translate this guidance cue information into structural changes which allow the growth cone to expand or collapse is largely unexplored. Recent evidence suggests that accurate growth cone guidance is absolutely dependent upon local protein synthesis. The functional corollary of this finding is that axon guidance requires RNA localisation and control of protein synthesis of RNAs in the growth cone. This phenomenon of spatial gene regulation within an individual cell is a central research interest for understanding how the brain functions.Read moreRead less