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Revealing the Landscape of Synaptic Diversity by Cell type- and Synapse-specific Proteomics and Transcriptomics

Objective

Synapses differ in their shape, size, and function and exhibit ongoing plasticity during the development and modification of neural circuits. The structural diversity of synapses is largely known whereas the molecular diversity of synapses is much less well understood. While most synaptic molecules have been identified by immunolabeling and bulk proteomic approaches, the complement of proteins present at individual synapse types, as well as their stoichiometric relationships with other molecules remains unknown. Indeed, our current classification mostly relies on neurotransmitter/receptor phenotypes, leading to broad descriptors like “excitatory” or “inhibitory” synapses. Because the function of the synapse, as well as its ability to change, is largely determined by the quality and quantity of molecules that inhabit it, it is essential to understand synaptic molecular diversity.

The aims of this proposal are to determine the proteomes and transcriptomes of genetically-identifiable synaptic populations in different brain areas and to determine the molecular diversity in these same synapse populations using transcriptomic analysis of individual synapses. We will also assess how these synaptic proteomes, transcriptomes and the transcriptomic diversity respond to plasticity.

To study synaptic proteomes and transcriptomes we will use Fluorescence-Activated Synaptosome Sorting to purify different synaptic populations (excitatory, inhibitory, dopaminergic) from different brain areas. We will use the state-of-the-art methods optimized for quantitative transcriptomic and proteomic profiling of very small amounts of sorted synapses and develop a method, SynDrops, for the transcriptomic analysis of individual synapses. We will examine how synaptic proteomes and transcriptomes change during plasticity. These studies will reveal the landscape of synaptic diversity within synapse types and across brain areas and allow the field to probe “diseased” synapses in the future.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-ADG

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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
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.

€ 2 498 575,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 498 575,00

Beneficiaries (1)

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