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Financement de l’UE (1 997 549 €) : Rapporteurs de gènes en microscopie électronique basés sur des nanocompartiments d’encapsuline issus de la bio-ingénierie Hor24/07/2020 Programme de recherche et d'innovation de l'UE « Horizon »
Vue d’ensemble
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Rapporteurs de gènes en microscopie électronique basés sur des nanocompartiments d’encapsuline issus de la bio-ingénierie
The biological engineering project EMcapsulins will create the first suite of multiplexed genetic reporters for electron microscopy (EM) to augment today’s merely structural brain circuit diagrams (connectomes) with crucial information on neuronal type and activation history. My team will generate this new toolbox based on genetically encoded nanocompartments of the prokaryotic ‘encapsulin’ family that we have recently shown to enable genetically controlled compartmentalization of multicomponent processes in mammalian cells. By encapsulating metal-organizing cargo proteins in the lumen of the semi-permeable encapsulin nanospheres, they serve as fully genetic EM gene reporters (EMcapsulins) that provide robust and spatially precise contrast by conventional EM in mammalian cells. To enable geometric multiplexing in EM in analogy to multi-color light microscopy, we will explore the large geometrical feature space of EMcapsulins to establish three core Functionalities: ① different shell structures and diameters, ② modular and tunable shell functionalizations, and ③ multiplexed and triggered cargo loading. We will combine these Functionalities to produce geometrically multiplexed EMcapsulin markers of neuronal identity in serial EM (Application ❶). We will also engineer EMcapsulin reporters for activity-dependent gene expression, calcium signaling, and synaptic activity that can ‘write’ geometrically encoded records of neuronal activation history into EM connectomics data (Application ❷). These ‘multi-color’ and modular EMcapsulin markers and reporters deliver the missing bridging technology between time-resolved light microscopy measurements of neuronal activation dynamics and structural EM connectomics data. EMcapsulin technology will convert structural to functional EM connectomes to enable a systematic analysis of how brains write molecular signaling dynamics into structural patterns to store information for later retrieval.
| HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GmbH | 225 000 € |
| TECHNISCHE UNIVERSITAET MUENCHEN | 1 772 549 € |
https://cordis.europa.eu/project/id/865710
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel.