SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Formation of the Chlamydial Inclusion Requires Host Trafficking Pathways. Using cellular and biochemical approaches this project aims to examine the membrane trafficking pathways hijacked by the pathogen Chlamydia and to define the key components of these pathways. Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen hijacks the host's membrane trafficking pathways to engineer an intracellular ....Formation of the Chlamydial Inclusion Requires Host Trafficking Pathways. Using cellular and biochemical approaches this project aims to examine the membrane trafficking pathways hijacked by the pathogen Chlamydia and to define the key components of these pathways. Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen hijacks the host's membrane trafficking pathways to engineer an intracellular niche called an inclusion. In addition to providing a permissive environment, this strategy also shields the pathogen from the host's immune system.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
Fyn-STEP-Tau axis: the nanoscale mechanisms of synaptic plasticity. This project investigates how brain cells use their molecular machinery to communicate with one another. At the heart of this process lies the synapses, the contact points that connect brain cells. This project will employ an innovative combination of quantitative microscopy techniques, gene knockout mouse models, and advanced computational and mathematical analyses to generate new knowledge on how a crucial set of proteins orga ....Fyn-STEP-Tau axis: the nanoscale mechanisms of synaptic plasticity. This project investigates how brain cells use their molecular machinery to communicate with one another. At the heart of this process lies the synapses, the contact points that connect brain cells. This project will employ an innovative combination of quantitative microscopy techniques, gene knockout mouse models, and advanced computational and mathematical analyses to generate new knowledge on how a crucial set of proteins organises in space and time to regulate synaptic connectivity. This will provide significant benefits, including molecular-level insight into the inner workings of the brain and interdisciplinary training for students. The expected outcomes include a deeper understanding of brain functions, such as learning and memory.Read moreRead less
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
Nuclear functions of the microtubule-associated protein tau. The important neuronal protein, tau, has cellular functions that go far beyond its established role in stabilising microtubules. This project will determine which tau species are nuclearly localised, what the consequences are for nuclear functions, and how phosphorylation regulates this localisation.
The role of actin in driving bulk endocytosis in neurons and neurosecretory cells. Synaptic release of neurotransmitter is essential for neuronal communication. Following fusion, synaptic vesicle membrane is incorporated into the plasma membrane and retrieved by endocytosis to recover both lipids and essential vesicular proteins. The project will characterise how the actin cytoskeleton perform this function.
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