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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.

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

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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