Project description
Multi-molecular connectomic mapping of mammalian brain tissue
Neuronal wiring forms the brain’s information network, but key questions about its organisation and cellular evolution remain unresolved. Current measurement technologies struggle to clarify connectivity and molecular characteristics, leaving these aspects disconnected in analysis. The ERC-funded MOLCONN project aims to develop optical imaging technologies for multi-molecular mapping and connectomic reconstruction. By integrating protein information and gene expression profiling, it will reveal cell types and intercellular signalling mechanisms. Using high-fidelity expansion microscopy, it will explore brain tissue architecture in mice during development and ageing and define organisational principles in human brain tissue. It will also analyse the ageing brain to relate genotype and disease states to functional outcomes in a Parkinson’s disease mouse model.
Objective
Complex wiring between neurons underlies the information processing network enabling all brain function. Fundamental questions on how the network is organized, how structural connectivity relates to the cells’ molecular machineries and how cells, synaptic connections, and circuits evolve over time remain enigmatic. Addressing these questions is beyond the limits of current measurement technologies, as these either lack resolving power to untangle cellular connectivity or can’t visualize the molecular characteristics of cells, such that these functionally highly interlinked modalities of information remain disconnected in current analysis.
Here, we will devise transformative optical imaging technologies for multi-molecular mapping in relation to dense, synaptic resolution connectomic reconstruction of the same cells. We will directly integrate multiplex protein information and in-situ gene expression profiling with connectomic reconstruction. This will reveal cell types and states and the molecular machineries involved in intercellular signaling mapped, onto neuronal morphology and synaptic connectivity patterns. The technology will be based on high-fidelity expansion microscopy with combined structural and multi-molecular readout. We will apply MOLCONN to study the functional architecture of brain tissue across development and ageing in healthy mice with unprecedented information content. We will then define multi-modal organizational rules in human brain tissue. Analysis of the ageing brain will serve as reference frame to bridge from genotype/disease states to tissue-level functional phenotypes in neurodegenerative disease in a mouse model of Parkinson’s disease.
We will use a uniquely cross-disciplinary approach integrating developments in imaging, sample preparation, molecular labeling, and computational data interpretation to build unified models of molecular and structural circuit properties to address the fundamental question of how these interrelate.
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 biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology neurodegenerative diseases parkinson
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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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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.
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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-2024-ADG
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3400 Klosterneuburg
Austria
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