Project description
Exploiting skull-meninges connections to control brain pathologies
As more and more people around the world are living longer, society is facing growing challenges arising from neurodegenerative diseases affecting millions of people. The recent discovery of the skull-meninges connections (SMCs) that can mediate immune cell trafficking into the brain is extremely promising for new diagnostics and treatments. However, the comprehensive cellular and structural features of the SMCs and the skull/calvaria need further research. The EU-funded CALVARIA project will use advanced experimental technologies of tissue clearing, proteomics and single-cell RNA sequencing to investigate possible exploitation of the discovery for easier access from the skull/calvaria bone marrow, enabling better drug delivery into the brain, control of neuroinflammation and easier detection of brain pathologies.
Objective
Neurodegenerative diseases (NDs) are labeled as the epidemic of the 21st century. The inflammation of the brain is a common pathology observed in many NDs. Here I aim to exploit our discovery of skull – meninges connections (SMCs) mediating immune cell trafficking into the brain to ease this healthcare burden. Using tissue clearing methods, we found that the skull (calvaria) bone marrow is directly connected to the brain meninges, a discovery that was also shown by an independent group around the same time. This finding suggests that the calvaria is involved in diverse brain pathologies. Easier accessibility of the calvaria compared to brain parenchyma also makes it an attractive region to target, which would alleviate hurdles of drug delivery into the brain, e.g. to control neuroinflammation. Furthermore, potential biomarkers in the calvaria reflecting pathologies of the brain could be easier and faster to detect. However, the detailed structural and cellular characteristics of the SMCs and the calvaria, and how they correlate and interact with neuropathology remain unknown. Here, we will utilize high-throughput technologies such as tissue clearing, single cell RNAseq, proteomics and unbiased analysis of data using deep learning to close this knowledge gap. We will use ischemic stroke and dementia models that are associated with acute and chronic neuroinflammation, respectively, and study both mouse and human tissues in parallel to validate potential clinical implications.
This project will investigate followings:
Aim 1 | Calvaria in physiological state
Aim 2 | Therapeutic aspect: manipulation of calvaria to control stroke and dementia
Aim 3 | Diagnostic aspect: calvaria imaging to monitor stroke and dementia
Thus, the first in-depth investigation of the calvaria bone in health and disease could deliver novel diagnostic and therapeutic targets to mitigate the increasing burden of neurological diseases.
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 proteomics
- medical and health sciences basic medicine neurology dementia
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine neurology stroke
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
Funding Scheme
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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.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-COG
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85764 Neuherberg
Germany
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