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Plasma membrane probes for photo-controlled release of signaling molecules

Project description

Visualising and controlling neural signalling

The eukaryotic plasma membrane (PM) is a dynamic cellular structure that facilitates diverse processes such as cellular uptake, cell communication, and signalling. It is of particular importance for neuronal signalling as it is implicated in neurotransmitter release and also houses key proteins implicated in neural activity. Funded by the Marie Skłodowska-Curie Actions programme, the MemCage project aims to create membrane-targeting fluorescent molecular tools for imaging of neurons and control of their activity by release of neurotransmitters under light stimulus. These tools will provide central insight into the generation and propagation of neuronal signals in health and disease.

Objective

The cell plasma membrane (PM) of eukaryotic cells is a highly dynamic structure, which plays important role in diverse biological processes such as cellular uptake, neural communication, muscle contraction, and cell trafficking and signaling. The PMs are also responsible for communication between cells, especially between neurons. In particular, the exocytosis process leads to liberation of neurotransmitters and neuromodulators. On the other hand, it is a platform for receptors that convert the recognition of neuroactive molecules into ion flux and/or action potential. Therefore, to modulate and monitor the activity of neurons, an attractive approach is to design molecular tools that target cell PMs. In this project, we will combine PM-targeting anchors with photoactive fluorescent cages capable to photo-release signaling molecules. The obtained chemical tools (MemCages) will be applied for 1) imaging the neuronal organization and 2) photo-controlled activation of neurons and brain of mice by photo-uncaging of signaling molecules close to PM. The work is composed of 3 steps. First is synthesis of MemCages for dopamine and glutamate and their validation in solvents and model lipid membranes. Second is application of MemCages in cellular systems, which includes imaging and photo-stimulation of model cancer cell lines and neurons. The first step will be in vivo validation of MemCages, which will be done during the secondment. The applicant and the host laboratory plan extensive two-way knowledge transfer: the applicant will gain knowledge and expertise in membrane probe design, bioimaging in model membranes, cells and animals, whereas he will provide his expertise on design and characterization of molecular photocages for signaling molecules. The successful utility of the developed chemical tools could open new avenues for the biologists and neuroscientists working in the field of cell signaling, neuroscience and diagnosis and prevention of neurological disorders.

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSITE DE STRASBOURG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 211 754,88
Address
RUE BLAISE PASCAL 4
67081 STRASBOURG
France

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Activity type
Higher or Secondary Education Establishments
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Total cost

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