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Electron Microscopy gene reporters based on bioengineered encapsulin nanocompartments

Objective

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.

Field of science

  • /humanities/history and archaeology/history

Call for proposal

ERC-2019-COG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

TECHNISCHE UNIVERSITAET MUENCHEN
Address
Arcisstrasse 21
80333 Muenchen
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 772 549

Beneficiaries (2)

TECHNISCHE UNIVERSITAET MUENCHEN
Germany
EU contribution
€ 1 772 549
Address
Arcisstrasse 21
80333 Muenchen
Activity type
Higher or Secondary Education Establishments
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany
EU contribution
€ 225 000
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Activity type
Research Organisations