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.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.
A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project a ....A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project aims to use sensory neurons derived from human stem cells to develop and optimise assays that can be used to study the pharmacology and function of human sensory neurons in vitro. This enhances access to critical model systems and technology platforms and removes the need for isolation of cells from cadavers. 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
Discovery Early Career Researcher Award - Grant ID: DE170100546
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Activity-dependent regulation of glutamate receptor trafficking in 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 not well understood. This project will use structural, biochemical, molecular and cell biological assays to study the molecular processes that control glutamate receptor trafficking in the ....Activity-dependent regulation of glutamate receptor trafficking in 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 not well understood. This project will use structural, biochemical, molecular and cell biological assays to study the molecular processes that control glutamate receptor trafficking in the postsynaptic compartment. It will elucidate how neural plasticity is generated and maintained, information critical for understanding sensory processing, learning and memory throughout life. The findings could identify cellular targets for interventions to enhance cognitive performance and maintain optimal brain function.Read moreRead less
Control of selective microRNA release via exosomes and microvesicles. This project aims to improve our understanding of cell-to-cell communication. Cells release genetic material including microRNAs in lipid membrane-enclosed vesicles (called exosomes and microvesicles) to alter neighbouring and distant cells. Recent research shows that the contents of these vesicles are regulated by cell state, however, the molecular mechanisms are not yet known. This project will investigate the hypothesis tha ....Control of selective microRNA release via exosomes and microvesicles. This project aims to improve our understanding of cell-to-cell communication. Cells release genetic material including microRNAs in lipid membrane-enclosed vesicles (called exosomes and microvesicles) to alter neighbouring and distant cells. Recent research shows that the contents of these vesicles are regulated by cell state, however, the molecular mechanisms are not yet known. This project will investigate the hypothesis that changes in the RNA-binding protein composition of cholesterol-rich membranes mediate the selection of miRNA loaded in the vesicles. This knowledge may increase our understanding of mechanisms of disease because this mode of cell-to-cell communication is disrupted or hijacked in pathologies. Future translation in diverse applications may improve human, animal and plant health.Read moreRead less
Adrenomedullin: a specific regulator of venous vessel integrity. Arteries and veins display different adhesive properties, which enable them to fulfil their physiological roles. We are yet to understand the mechanisms that establish and maintain adhesive function in different vessel types. We have discovered that signalling by the peptide Adrenomedullin (ADM) is a key mediator of adhesion, only in veins but not arteries. This project aims to utilise innovative models (zebrafish, mouse and bioeng ....Adrenomedullin: a specific regulator of venous vessel integrity. Arteries and veins display different adhesive properties, which enable them to fulfil their physiological roles. We are yet to understand the mechanisms that establish and maintain adhesive function in different vessel types. We have discovered that signalling by the peptide Adrenomedullin (ADM) is a key mediator of adhesion, only in veins but not arteries. This project aims to utilise innovative models (zebrafish, mouse and bioengineered vessels) to identify the biochemical and mechanical mechanisms by which ADM controls venous adhesion. Outcomes will improve our understanding on how vessel integrity is controlled across vessel types and will expand the scope of Australian research by informing efforts to vascularise engineered tissues.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100524
Funder
Australian Research Council
Funding Amount
$365,057.00
Summary
Manipulating selected inflammatory responses in macrophages. This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to effect the inflammatory pathway. The project outcomes will include the first structure of this unconventional complex. The project will have significant flow on benefits including new knowledge and new protein methodologies for end-users in research and industry, and ultimately economic impact.
Tuning the activating stimulus of voltage-gated sodium channels. This proposal aims to advance fundamental knowledge about how proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. We aim to study how molecular probes and structural parts of these proteins affect the local chemical environment of ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that ....Tuning the activating stimulus of voltage-gated sodium channels. This proposal aims to advance fundamental knowledge about how proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. We aim to study how molecular probes and structural parts of these proteins affect the local chemical environment of ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that activates them (cell membrane voltage).
The conceptual knowledge gained from this project would advance our understanding of a fundamental physiological process and facilitate the development of drugs that regulate ion channel function, such as anti-epileptics, analgesics and insecticides.Read moreRead less