Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be ....Old brain cells perform new tricks to allow life-long learning. In the brain, nerve cells transmit electrical signals more quickly and reliably when they are insulated. The insulating cells undergo small adaptive changes that speed up information transfer during learning, and the faster the electrical signal, the better the learning outcomes. This project aims to understand the signals that direct insulating cells to adapt and support life-long learning. In the longer term, this knowledge may be used to: develop interventions that improve learning and educational outcomes; counteract age-related memory decline and enable longer work force participation; develop strategies to circumvent the memory loss caused by brain diseases, or improve the design of computer hardware.Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Intra and intermolecular steps underpinning vesicular priming. This project aims to discover how secretory vesicles fuse with the plasma membrane, a process called priming. The fusion of secretory vesicles by exocytosis underpins neuronal communication. Despite efforts to understand vesicular fusion, how these vesicles become fusion-competent upon arrival at the plasma membrane is unknown. This project will use single molecule imaging to assess mobility changes of key priming molecules and uncov ....Intra and intermolecular steps underpinning vesicular priming. This project aims to discover how secretory vesicles fuse with the plasma membrane, a process called priming. The fusion of secretory vesicles by exocytosis underpins neuronal communication. Despite efforts to understand vesicular fusion, how these vesicles become fusion-competent upon arrival at the plasma membrane is unknown. This project will use single molecule imaging to assess mobility changes of key priming molecules and uncover their diffusional signature during priming. It intends to build a comprehensive model of molecular interactions that make a recently docked vesicle fusion-competent. This understanding is key to unravelling how the brain worksRead moreRead less
Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds ....Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds of fusion. This recycling process ensures that neurons communicate efficiently, however the underpinning mechanism is unknown. This project aims to use a recently developed single synaptic vesicle super-resolution tracking method to establish how Myosin-VI and Synapsin-IIa orchestrate this recycling in central and peripheral neurons. It will explain how neurons manage to preserve their ability to communicate.Read moreRead less
Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following ner ....Microtubule structure in nervous system repair. This Project aims to investigate the role of structural and functional cellular components known as microtubules in nervous system regeneration. This Project aims to use innovative approaches in confocal and electron microscopy, genetics, and cell biology, with the expectation of generating new knowledge into nervous system repair. Expected outcomes of this Project include a comprehensive description of how microtubules are rearranged following nervous system injury and the importance of microtubule modifying proteins in promoting regeneration. This should provide significant benefits in our understanding of the cellular mechanisms behind nervous system repair, and offer new approaches for promoting regeneration after injury.Read moreRead less
The processing of sensory information within cortical circuits. This project aims to improve our knowledge of neuronal activity during sensory perception and therefore shed light on overall brain function during behaviour. Understanding how dendrites receive and process this information is crucial to understanding brain function during sensory processing and perception. This proposal aims to characterise dendritic activity during sensory input and discover how this activity contributes to behavi ....The processing of sensory information within cortical circuits. This project aims to improve our knowledge of neuronal activity during sensory perception and therefore shed light on overall brain function during behaviour. Understanding how dendrites receive and process this information is crucial to understanding brain function during sensory processing and perception. This proposal aims to characterise dendritic activity during sensory input and discover how this activity contributes to behavioural tasks. In particular, the project plans to investigate activity of different dendritic domains during sensory perception and sensory-based behaviour. The project seeks to improve our knowledge of the importance of dendrites in transforming information from the sensory environment and highlight the cellular and network mechanisms contributing to behaviour.Read moreRead less
The role of tropomyosin in coordinated neurite branching. This project will explore how nerve cells generate a highly branched network of cell processes which allows all higher functions of the nervous system. We previously discovered the central role of a component of the cell architecture in determining the branching pattern and in this project expect to reveal the molecular basis for its function.
Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously ....Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously, whilst recording intestinal muscle electrical activity and the movements of the gut wall, the project expects to identify which enteric neurochemical classes of neurons generate specific motor patterns along the intestine.Read moreRead less
Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly qui ....Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly quiescent, dividing rarely to ensure that they are not prematurely exhausted. However, the factors that maintain this quiescence are very poorly defined. The project aims to understand how stem cell quiescence is controlled at both a molecular and cellular level in vivo within the adult mouse brain.Read moreRead less
Subcellular recruitment of a RhoA ubiquitination complex by Rnd proteins. This study addresses a novel molecular mechanism through which members of the Rnd family of GTP-binding proteins regulate the morphology and migration of immature nerve cells of the developing nervous system. This study has broad implications for the understanding of cell migration during embryo development, as well as in health and disease.