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ADIPOR SIGNED

Molecular and structural pharmacology of adiponectin receptor: towards innovative treatments of obesity-related diseases.

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

ADIPOR project word cloud

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

lack groundbreaking complexes characterization cells obtaining lifespan human energy witnessing agonists ameliorates pharmacology combining data action adiponectin justifies gap structure living activation receptors genetically prolongs fill health transfer strategy risks interaction rodent atypical integral physiology diseases revealed small obese innovative network discovery drug extensive gain risk function endeavor treating biophysics complete modulation mainly direction molecular proteomic escalation of silico exceptionally adipor biochemistry model resonance mechanisms molecules screening ray obesity membrane despite protein career diabetes biology cardiovascular crystallography feasibility signaling proximal structural

Project "ADIPOR" data sheet

The following table provides information about the project.

Coordinator	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Organization address address: RUE DE TOLBIAC 101 city: PARIS postcode: 75654 website: www.inserm.fr 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	France [FR]
Total cost	1˙989˙518 €
EC max contribution	1˙989˙518 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2014-CoG
Funding Scheme	ERC-COG
Starting year	2015
Duration (year-month-day)	from 2015-07-01 to 2020-06-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Organization address address: RUE DE TOLBIAC 101 city: PARIS postcode: 75654 website: www.inserm.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	coordinator	1˙989˙518.00

Map

Project objective

The human kind is witnessing an escalation of obesity-related health problems such as cardiovascular diseases and type 2 diabetes. A recent groundbreaking study revealed adiponectin receptors (ADIPOR) as key targets for treating such obesity-related diseases. Indeed, the modulation of this integral membrane protein by small molecules agonists ameliorates diabetes and prolongs lifespan of genetically obese rodent model. Despite these exciting results and the importance of ADIPOR in human physiology, there is a complete lack of knowledge of ADIPOR mechanisms of action and pharmacology. This is mainly due to the challenges associated with the characterization of membrane protein structure and function. To fill this gap of knowledge and based on my extensive experience in membrane protein biology, I propose here to characterize the the proximal signaling pathways associated with ADIPOR activation as well as the molecular and structural mechanisms of ADIPOR activation. We will develop an innovative integrated strategy combining state-of-the-art molecular and structural pharmacology approaches including 1) molecular analyses of ADIPOR network of interaction using resonance energy transfer measurement in living cells and a proteomic analysis and 2) structural analyses of ADIPOR and signaling complexes using biophysics and X-ray crystallography. Our data will have a major impact on drug discovery for treating obesity-related diseases as it will enable the application of structure-based drug design and in silico screening for the molecular control of ADIPOR activity. The proposed high-risk endeavor of obtaining structural data on these atypical membrane signaling complexes is a new direction both for my career and for the field of adiponectin biology; the exceptionally high gain from these studies fully justifies the risks; the feasibility of this project is supported by my recent success in membrane protein pharmacology, biochemistry, biophysics and crystallography.

Publications

List of publications.
year	authors and title	journal	last update
2017	Ieva VasiliauskaitÃ©-Brooks, Remy Sounier, Pascal Rochaix, GaÃ«tan Bellot, Mathieu Fortier, FranÃ§ois Hoh, Luigi De Colibus, ChÃ©rine Bechara, Essa M. Saied, Christoph Arenz, CÃ©dric Leyrat, SÃ©bastien Granier Structural insights into adiponectin receptors suggest ceramidase activity published pages: 120-123, ISSN: 0028-0836, DOI: 10.1038/nature21714	Nature 544/7648	2019-06-06

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