Project description
Molecular connectomics: untangling synapse-specific connectivity
Behaviour, emotion and cognition are macroscale phenomena relying on the brain’s vast number of cells and even greater number of synapses. The human genome plays a key role in the development of this symphony of interconnectedness. Untangling how the genomic information leads to synapse-specific connectivity is critical to fundamental understanding of the nervous system and nervous system development. It is also essential to understanding and treating nervous system dysfunction. The ERC-funded SpaRC project aims to develop an innovative approach for tracing massively parallel neural circuitry leveraging barcoded rabies virus and 3D intact-tissue RNA-sequencing. It will enable large-scale measurement of molecular, cellular, and circuit-level mechanisms, shedding light on the brain’s neural networks in health and disease.
Objective
The human genome contains several thousand genes that play a key role in the development of the brains connectome, a precise assembly of neural connections with billions of neurons and trillions of synapses. How is genomic information translated into synapse-specific connectivity underlying behavior and cognition? Answering this fundamental question will provide important insights about the principles underlying nervous system development and is relevant for neurodevelopmental disorders such as autism. However, current approaches to measure neuronal connectivity have intrinsic limitations that prevent combined analysis of connected neurons, and their gene expression profiles at a scale that matches the complexity of the mammalian nervous system. Here I propose to develop a novel approach for massively parallel neural circuit tracing with barcoded rabies virus and 3D intact-tissue RNA-sequencing. This will permit a comprehensive understanding about neural network architecture via the large-scale measurement of molecular, cellular, and circuit-level mechanisms in the mouse brain. Compared to current efforts that require vast scientific resources to map synaptic connectivity among a few cells or small tissue volumes, my approach will enable routine measurements of connections among thousands of single neurons with molecular detail. Based on my expertise in in vivo barcoding I will conduct a longitudinal study to reveal the wiring rules underlying the spatiotemporal development of neural circuits from diverse neuron types in the mouse prefrontal cortex, a brain region that plays a key role in cognition. I will follow a cross-sectional approach to unravel the effects of distinct mutations on neuronal wiring in the prefrontal cortex in two mouse models of autism (Cntnap2-/-, Syngap1+/-). My work will provide an innovative experimental platform and provide mechanistic insights into the developmental algorithms that the genome uses to encode the connectome.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-STG
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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.
171 77 STOCKHOLM
Sweden
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