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Content archived on 2024-06-10

The mechanism of retrograde transport in neurons

Objective



Research objectives and content Definition of the membrane dynamics at the nerve e terminal is one of the challenging frontiers in neurobiology. In recent years, the intracellular proteolytic activity of clostridial neurotoxins has been proven to be essential for studying neurosecretion,especially for the processes of docking and fusion of neurotransmitter-containing vesicles with the plasma membrane. Furthermore, the absolute neurospecificity and the distinct intraneuronal pathways of these neurotoxins make them useful tools to further the understanding of other important aspects of nerve terminal physiology. In particular,I am proposing to use the tetanus toxin binding fragment as a tool to unravel the molecular mechanism of retrograde transport and transcytosis in nerve cells through the characterization of its neuronal-specific receptor. The accomplishment of this goal will elucidate an important and still poorly understood neuronal transport mechanism and will disclose a new strategy for the delivery of pharmacologically active substances to the central nervous system. Training content (objective. benefit and expected impact) The identification of the receptor for tetanus toxin will peroxide valuable data as well as new tools for the study of the retrograde transport mechanism and will be a step-forward in the understanding of the cell biology of neurons. Furthermore, the achievement of this objective will reveal the strategy developed by this neurotoxin to specifically enter into neurons, a feature shared also by several viruses. This finding will be very useful for the delivery of drugs with clinical interest into the nervous system. The present research project will combine a relevant training on cellular, biochemical and molecular biology techniques that will be extremely useful for me in my return to a spanish laboratory. Links with industry / industrial relevance (22)

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Topic(s)

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Funding Scheme

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RGI - Research grants (individual fellowships)

Coordinator

Imperial Cancer Research Fund
EU contribution
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Address
Lincoln's Inn Fields 44
WC2A 3PX London
United Kingdom

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Total cost

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