Deciphering Signalling Pathways Regulating Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$407,402.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia.
Organising Intracellular Compartments by Formation of Transport Carriers. This project aims to investigate the cellular components which generate carriers that transport material between compartments within the cell. The process of sorting proteins and sending them to the right place is a fundamental mechanism critical to understand how individual proteins function as the move around within cells. The generated knowledge about how cells organise themselves through the movement of proteins betwee ....Organising Intracellular Compartments by Formation of Transport Carriers. This project aims to investigate the cellular components which generate carriers that transport material between compartments within the cell. The process of sorting proteins and sending them to the right place is a fundamental mechanism critical to understand how individual proteins function as the move around within cells. The generated knowledge about how cells organise themselves through the movement of proteins between endosomal intracellular compartments will provide significant benefits by enhancing our capacity to understand this conserved cellular pathway which ensures the integrity of all cellular processes including signalling, communication, homeostasis and development.Read moreRead less
Defining the membrane protein cargo transported by Retromer. This project aims to define the role of Retromer, a protein machine that directs the organisation and movement of proteins within the cell. The function of proteins is dependent on how they travel through the various regions or compartments within the cell. One intracellular compartment, termed endosomes, is central to this dynamic process. Intracellular transport of biomolecules through the endosomal organelle is critical for normal c ....Defining the membrane protein cargo transported by Retromer. This project aims to define the role of Retromer, a protein machine that directs the organisation and movement of proteins within the cell. The function of proteins is dependent on how they travel through the various regions or compartments within the cell. One intracellular compartment, termed endosomes, is central to this dynamic process. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling and development. Endosomal transport occurs within membrane domains and membrane vesicular carriers formed by Retromer. This project aims to define the transmembrane proteins sorted by the distinct retromer complexes that form within the cell and the sorting signals essential for their correct trafficking and localisation.Read moreRead less
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less
Understanding Changes In The Mammalian Prenylome Induced By Statins And Prenyltransferase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Prenylation, the covalent attachment of isoprenoid lipids to proteins, is widespread in mammalian cells. Essential for a protein's normal function, it contributes to the progression of cancer and inflammation. We have developed a novel technology to identify all prenylated proteins in the cell. Aided by this method, we will analyse the effect of statins and anti-cancer drugs on protein prenylation. This will provide guidance in identifying a more effective clinical use for them.
The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determinat ....Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determination. The underpinning experimental technology, termed reverse transfection arrays, allows for high-throughput assessment of cellular phenotype properties for individual proteins.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL210100107
Funder
Australian Research Council
Funding Amount
$2,960,000.00
Summary
Tracking nanoparticles: from cell culture to in vivo delivery. Understanding how cells function in the ‘real-time’ context of a living organism is a key challenge in the new era of cell biology. Using super-resolution light microscopy and state-of-the-art correlative electron microscopy together with model systems, this Fellowship aims to deliver new understandings of cells in their natural environment. Significantly, the project will elucidate how proteins or nanoparticles pass from the bloodst ....Tracking nanoparticles: from cell culture to in vivo delivery. Understanding how cells function in the ‘real-time’ context of a living organism is a key challenge in the new era of cell biology. Using super-resolution light microscopy and state-of-the-art correlative electron microscopy together with model systems, this Fellowship aims to deliver new understandings of cells in their natural environment. Significantly, the project will elucidate how proteins or nanoparticles pass from the bloodstream into tissues and then into cells, and in doing so deliver much-needed knowledge of protein and particle trafficking in situ. Outcomes and benefits include leading-edge fundamental science into the function of cells, education, outreach and building of Australian capacity in high-demand skill sets.Read moreRead less
Regulation of glutamate receptor dynamics in mammalian central neurons. This proposal aims to understand the molecular mechanisms of neuronal communication and how neurons modify their synaptic strength. Although these processes are essential for normal brain function, the precise underlying mechanisms are still not well understood. This project will combine biochemical, molecular and cell biological assays, as well as electrophysiological measurements, to provide mechanistic insights into the m ....Regulation of glutamate receptor dynamics in mammalian central neurons. This proposal aims to understand the molecular mechanisms of neuronal communication and how neurons modify their synaptic strength. Although these processes are essential for normal brain function, the precise underlying mechanisms are still not well understood. This project will combine biochemical, molecular and cell biological assays, as well as electrophysiological measurements, to provide mechanistic insights into the molecular processes that control glutamate receptor trafficking in the postsynaptic compartment. This will elucidate how neural plasticity is generated and maintained, information that is critical for our understanding of sensory processing, learning and memory throughout life.Read moreRead less
Regulation of activity-induced glutamate receptor trafficking in neurons. Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate the role of a calcium binding protein i ....Regulation of activity-induced glutamate receptor trafficking in neurons. Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate the role of a calcium binding protein in controlling glutamate receptor trafficking in neurons. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition. Read moreRead less