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EMERGE SIGNED

Epigenetic and metabolic regulation of endothelial heterogeneity

Total Cost €

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EC-Contrib. €

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Partnership

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Project "EMERGE" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

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 Germany [DE]
 Project website https://www.angio-met-lab.com
 Total cost 1˙998˙750 €
 EC max contribution 1˙998˙750 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2023-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 1˙998˙750.00

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 Project objective

Heterogeneity within the endothelium is increasingly recognized in both normal and disease conditions, influencing vascular architecture, structure, and function. The diverse phenotypes that endothelial cells (ECs) adopt suggest substantial plasticity and indicate that heterogeneity is a core property that enables ECs to fulfill their tissue-specific tasks. However, the molecular basis for tissue-specific endothelial differentiation and heterogeneity remains largely unknown. In this project, we will study the impact of environmental context on endothelial specialization and focus on the emerging relationship between metabolism, epigenetics, and cellular differentiation. We hypothesize that organ-specific differences in endothelial metabolic state, through altered epigenetics, promote specialization and thereby contribute to heterogeneity within the vascular system. The proposal rests on the notion that many of the enzymes that erase epigenetic modifications (from DNA and histones) are exquisitely sensitive to changes in metabolism as they utilize cosubstrates that are generated by cellular metabolism. Using a combination of state-of-the-art genetics, high-resolution imaging, metabolomics, and biochemistry, we will study the role of these epigenetic mechanisms for general and organ-specific blood vessel formation (Objective I) and determine their regulation by metabolic and vascular differentiation signals (Objective II). Moreover, we will explore whether metabolic changes during obesity and aging impact the maintenance of endothelial specialization, and assess whether deregulation of metabolic-epigenetic signalling leads to endothelial malfunction and organ failure (Objective III). We trust that the knowledge gained through this project will provide a conceptual framework for understanding how environmental context can drive vascular heterogeneity and, more generally, how alterations in metabolism and nutrition might contribute to vascular-related diseases.

 Publications

year authors and title journal last update
List of publications.
2019 Lim R, Sugino T, Nolte H, Andrade J, Zimmermann B, Shi C, Doddaballapur A, Ong YT, Wilhelm K, Fasse JWD, Ernst A, Kaulich M, Husnjak K, Boettger T, Guenther S, Braun T, Krüger M, Benedito R, Dikic I, Potente M
Deubiquitinase USP10 regulates Notch signaling in the endothelium
published pages: 364(6436):188-19, ISSN: 0036-8075, DOI:
Science 2019-10-30
2018 Meghan Riddell, Akiko Nakayama, Takao Hikita, Fatemeh Mirzapourshafiyi, Takuji Kawamura, Ayesha Pasha, Mengnan Li, Mikio Masuzawa, Mario Looso, Tim Steinbacher, Klaus Ebnet, Michael Potente, Tomonori Hirose, Shigeo Ohno, Ingrid Fleming, Stefan Gattenlöhner, Phyu P. Aung, Thuy Phung, Osamu Yamasaki, Teruki Yanagi, Hiroshi Umemura, Masanori Nakayama
aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA-binding ability
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07739-0
Nature Communications 9/1 2019-10-30
2018 Radiance Lim, Michael Potente
Top-NOTCH Regulation of Cardiac Metabolism
published pages: 2609-2612, ISSN: 0009-7322, DOI: 10.1161/circulationaha.118.033669
Circulation 137/24 2019-10-30
2019 Jorge Andrade, Michael Potente
Endothelial metabolism—more complex (III) than previously thought
published pages: , ISSN: 2522-5812, DOI:
Nature Metabolism 2019-10-30
2018 Oliver A. Stone, Mohamed El-Brolosy, Kerstin Wilhelm, Xiaojing Liu, Ana M. Romão, Elisabetta Grillo, Jason K. H. Lai, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne, I-Ching Lee, Thomas Braun, Massimo M. Santoro, Jason W. Locasale, Michael Potente, Didier Y. R. Stainier
Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06406-8
Nature Communications 9/1 2019-10-30

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