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Development of biomolecular tools for the spatiotemporal photocontrol of AMPA receptors mobility

Project description

Uncovering how AMPA receptors affect brain plasticity

Brain plasticity, also known as neuroplasticity, refers to the brain's ability to change and adapt as a result of experience. A known molecular mechanism for synaptic plasticity involves the AMPA glutamate receptor. This is an ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system. Its regulation plays an important role in learning and memory. The EU-funded PhotoXLink project will develop novel optogenetic tools (photocrosslinkers) that will specifically recognise AMPA receptor subunits and control their oligomeric state. The new tools will allow researchers to investigate with unprecedented spatiotemporal resolution, the impact of AMPA receptor mobility on short- and long-term brain plasticity.

Objective

The PhotoXLink project aims to develop original tools to elucidate the role of various AMPA receptor mediated forms of plasticity in both physiological and pathological situations. AMPAR is a transmembrane ionotropic receptor for glutamate molecule that mediates most fast excitatory synaptic transmission in the mammalian central nervous system. Its regulation is vital for their synaptic function, which underlies memory and learning theories. In the PhotoXLink project, we propose to engineer novel optogenetic tools (photocrosslinkers) that will specifically recognize AMPAR subunits and control their oligomeric state with spatial and temporal resolution. The photocrosslinkers will hence provide a unique control locally, acutely and in a reversible manner on the mobility and local number of AMPARs. The development of these photocrosslinkers will address current technical limitations and ultimately allow investigating with an unprecedented spatiotemporal resolution the impact of AMPARs mobility in short and long term plasticity in the brain function.
The multidisciplinary nature of the project is strong, involving molecular/cell biology, biochemistry and protein engineering for the design and production of the tools and advanced fluorescence imaging techniques for validating them in cellular context. It will be carried out at an internationally recognized neuroscience institute that will enhance my skills and diversify my individual competences through advanced training and quality research for improving my future career development. My expertise in photochemistry and photobiology combined with the host´s in neurobiology and protein engineering ensures the best chance for successfully fulfil the goals of the PhotoXLink project. This project is in line with the brain research priority for EU research funding.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-ST - Standard EF

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 184 707,84
Address
RUE MICHEL ANGE 3
75794 Paris
France
Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 184 707,84