H2020Индивидуална стипендия2019–2021

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-07-01 → 2021-10-30
Финансиране от ЕС: 184 708 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Рецепторите AMPA в мозъка и тяхното движение между различните части на невроните се контролират чрез светлина. Това помага да се разбере как се формират паметта и ученето, както и как работят синапсите при нормални и патологични състояния.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

The understanding of learning and memory in our brain at cellular and molecular levels, and specifically, the role of AMPA receptors’ mobility regulation at the synaptic site in neurons is of special interest. The regulation of AMPAR trafficking is crucial to its synaptic function. Indeed, the widely accepted model at present is that AMPARs are in dynamic equilibrium between synaptic, extrasynaptic and intracellular compartments. The changes in this equilibrium, affects AMPAR numbers at the synaptic sites what underlies long term plasticity of the efficacy of synaptic transmission, such as LTP (long term potentiation) and LTD (long term depression). This dynamic regulation is the basis of current molecular theories of learning and memory. Despite being a core locus of molecular information storage, the nature of this regulation is not yet completely understood because of the lack in technical tools. The principal aim of this project was to develop innovative methods to control AMPAR mobility, and to monitor the resulting effects with unique spatial and temporal resolution. This addressed technical limitations and allowed investigating with a unique spatiotemporal resolution the impact of AMPARs mobility in short and long term plasticity in the brain function. More precisely, we aimed to design tools that provide a control of endogenous or genetically modified AMPARs mobility by way of light-controlled crosslinking. This project consisted on developing innovative methods to photoreversibly control receptor clustering/stabilization in order to be able to investigate how the dynamics of AMPAR is linked to the functional properties of synaptic transmission in normal and pathological brain states. I used a two-step strategy to achieve our goals, where we first focused on the photosensitive domain optimization and then implemented our work to more efficient binders. The project was organized around the following three objectives: (1) Design and production of a first generation of photocrosslinkers, (2) Validate and characterize the system in cellular environments and (3) Expand the photocrosslinking systems to minimally invasive epitope/binder pairs (2nd generation photocrosslinkers).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция