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CESYDE SIGNED

Ceramide Synthases in Diabetic Beta Cell Demise

Total Cost €

0

EC-Contrib. €

0

Partnership

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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.

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

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

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 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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