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CESYDE SIGNED

Ceramide Synthases in Diabetic Beta Cell Demise

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 CESYDE project word cloud

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

impair    cells    ceramide    worldwide    messenger    subcellular    membranes    tissue    functionally    inhibition    insulin    protective    animal    dependent    patients    building    enzymes    lipidomics    molecules    ameliorate    generate    protein    determined    expressed    sphingolipids    nutrients    regulated    biosynthesis    death    validate    inhibitors    six    pharmacological    proteins    modulating    downstream    crosslinking    indicate    specificity    million    combine    de    blocks    events    proteomics    beta    ceramides    synthesis    dysfunction    chain    dynamically    synthase    suffer    novo    mechanisms    post    lengths    prevent    diabetes    translational    intracellular    lipid    modulators    biology    400    regulatory    deleterious    human    localisation    mouse    genomics    manner    turn    cell    function    proliferation    systemic    act    functional    total    interacting    stress    metabolism    medical    mediating    modifications    cers    secretion    unknown    sum    tested    synthases    data    pancreatic    roles   

Project "CESYDE" data sheet

The following table provides information about the project.

Coordinator
DEUTSCHE DIABETES FORSCHUNGSGESELLSCHAFT EV 

Organization address
address: AUF M HENNEKAMP 65
city: DUESSELDORF
postcode: 40225
website: n.a.

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]
 Total cost 1˙492˙313 €
 EC max contribution 1˙492˙313 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-01-01   to  2022-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DEUTSCHE DIABETES FORSCHUNGSGESELLSCHAFT EV DE (DUESSELDORF) coordinator 1˙492˙313.00

Map

 Project objective

Sphingolipids including ceramides are building blocks of cell membranes, but also act as regulated intracellular messenger molecules. Emerging data indicate that sphingolipids are dynamically regulated by nutrients, and in turn control systemic metabolism, for example, by modulating insulin secretion, proliferation and cell death of pancreatic beta cells. Dysfunction and death of beta cells are key events during the development of diabetes, from which more than 400 million patients suffer worldwide. While pharmacological inhibition of general ceramide biosynthesis is protective against diabetes in animal studies, side effects of total loss of ceramides prevent medical implementation. The de novo synthesis of ceramides is fully dependent on six ceramide synthase enzymes (CerS 1-6), which are expressed in a tissue specific manner, and generate ceramides with different chain lengths. Currently, the functional roles and regulatory modulators of each CerS are unknown in pancreatic beta cells. Importantly, the downstream mechanisms by which ceramides impair beta cell function and eventually cause diabetes are not defined. Here, I propose to combine genomics, proteomics and lipidomics to assess the function of ceramide synthases expressed in mouse and human beta cells. Furthermore, both the subcellular localisation and the post-translational modifications of CerS will be determined. The ceramide-interacting proteins mediating the deleterious effects of ceramides will be identified by lipid-protein crosslinking and functionally tested. Finally, in a translational approach, we will test the ability of recently generated novel specific CerS inhibitors with improved specificity to ameliorate beta cell stress, and improve insulin secretion in mouse and human beta cells. In sum, we will identify, characterize, validate and target ceramide synthases involved in beta cell biology and development of diabetes.

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

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