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
Discovery Early Career Researcher Award - Grant ID: DE160100293
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a l ....Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a lipid-binding module found in numerous proteins essential for normal cell trafficking and homeostasis, and perturbed in many conditions including immune dysfunction and cancer. This project plans to investigate molecular determinants of PX-lipid association, generating knowledge about protein-membrane interactions required for cellular function. These insights may underpin future drug design.Read moreRead less
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
Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental und ....Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental understanding of how SNXs control this process, and the work will significantly strengthen our international collaboration in this emerging area. The knowledge has potential future translation in the treatment of neurodegenerative disorders where dysregulation of these proteins is known to cause disease.Read moreRead less
Understanding the basic biology of cells will allow us to pinpoint key mechanisms and molecules that underpin multiple diseases and are targets for treatments. The broad aims of this research program include the development of new therapies for chronic inflammatory diseases, understanding how proteins are sorted and trafficked inside cells in processes that are essential to immunity and cancer biology, and identifying new intracellular targets to block bacterial invasion and infectious diseases.
How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Ke ....How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Key to this process are membrane dynamics during synaptic vesicle retrieval, but the precise underlying mechanisms are not well understood. The intended outcome of this project is insights into the molecular mechanisms of synaptic transmission, the fundamental process of brain function, increasing understanding of physiological processes such as muscle movement, vision, hearing, touch, learning and memory.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100078
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Live molecular imaging using super resolution microscopy, two photon and spinning disk confocal microscopy. With recent developments of super-resolution microscopy it is now feasible to image single molecules within the cellular environment in living cells. Such insight is key to understanding basic biological interactions that govern the wiring of our brain, communications between cells and neurons and cell-cell adhesion.