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MechAGE SIGNED

In Vivo Single-Cell Mechanomics of Bone Adaptation and Regeneration in the Aging Mouse

Total Cost €

EC-Contrib. €

Partnership

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MechAGE project word cloud

Explore the words cloud of the MechAGE project. It provides you a very rough idea of what is the project "MechAGE" about.

data reporter regulated isolated environments crispr combining partly multiscale single fluorescent maximize diseases osteoporosis run mediated lapsed regulation rna simulations therapies load modeling mechanisms proposes fracture laser quality generate cells attributed mass cellular exploited signals mechanomics 3d computational microdissection multiple expression spatio bone ct vivo identification mechanomic investigation hundreds mice cas environment cell world local time technologies sequencing live degenerative risk mouse governing aging molecular remodeling gene interactions events micro transcriptome underlying decrease regeneration mechage models unclear resolved prevalent skeleton mechanical mechanobiology silico capture types temporal finite link tissue omics

Project "MechAGE" data sheet

The following table provides information about the project.

Coordinator	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Organization address address: Raemistrasse 101 city: ZUERICH postcode: 8092 website: https://www.ethz.ch/de.html contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Switzerland [CH]
Total cost	2˙500˙000 €
EC max contribution	2˙500˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-ADG
Funding Scheme	ERC-ADG
Starting year	2017
Duration (year-month-day)	from 2017-10-01 to 2022-09-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Organization address address: Raemistrasse 101 city: ZUERICH postcode: 8092 website: https://www.ethz.ch/de.html contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	CH (ZUERICH)	coordinator	2˙500˙000.00

Map

Project 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.

Publications

List of publications.
year	authors and title	journal	last update
2018	Graeme R. Paul, Angad Malhotra, Ralph MÃ¼ller Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals published pages: 395-403, ISSN: 1544-1873, DOI: 10.1007/s11914-018-0448-6	Current Osteoporosis Reports 16/4	2019-08-06

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The information about "MECHAGE" are provided by the European Opendata Portal: CORDIS opendata.