Objective
Osteoporosis, one of the most prevalent degenerative diseases, is characterized by a reduction in bone mass and increased fracture risk and has been partly attributed to the decrease in mechanical usage of the skeleton. A detailed understanding of the molecular mechanisms governing load-regulated bone remodeling could therefore lead to the identification of molecular targets for the development of novel therapies. Bone remodeling is a multiscale process mediated through complex interactions between multiple cell types and their local 3D environments. However, the underlying mechanisms of how cells respond to mechanical signals are still unclear. By combining single-cell “omics” technologies with well-established tissue-scale models of bone mechanobiology, MechAGE proposes to develop the technology required to allow spatially resolved in vivo single-cell mechanomics of bone adaptation and regeneration. CRISPR/Cas technology will be exploited to generate fluorescent reporter mice to identify the different cell types involved in the bone remodeling process. By combining RNA-sequencing of single cells isolated by laser-capture microdissection with micro-finite element analysis and time-lapsed in vivo micro-CT, MechAGE will link the transcriptome of hundreds of single cells to their local mechanical in vivo environment (LivE). This will allow investigation of molecular responses of the cells to LivE changes with aging in established mouse models of bone adaptation and regeneration. In addition to in vivo mechanomics, MechAGE proposes to use cellular and multiscale computational modeling to run in silico simulations of real-world events for better understanding of diseases of aging in mice and to maximize the use of the high quality in vivo mechanomic data. Findings from MechAGE will lead to a systems level understanding of the spatio-temporal regulation of gene expression during the process of load-induced bone adaptation and regeneration in the aging mouse.
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)
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.
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
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.
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-ADG - Advanced 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-2016-ADG
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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.
8092 Zuerich
Switzerland
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