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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine endocrinology diabetes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-STG - Starting Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2017-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
40225 Duesseldorf
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.