Objective
A principal cause of failure in the treatment of cancer is that cancer cells develop resistance to chemo- and radiotherapy, leading to recurrence of the disease or even death. Sphingolipid molecules can modulate the ability of malignant cells to grow and resist anticancer regimens, with some molecules promoting tumorigenesis and others acting as tumor-suppressors. The tumor-suppressor activity of ceramides has prompted development of different formulations of synthetic ceramides in anticancer therapies, but the poor solubility of these compounds restricts their biocompatibility. Therefore, attention is increasingly focused on possibilities to manipulate cellular sphingolipid balances from within.
The recent discovery of a ceramide sensor that protects cells against ceramide-induced cell death marks an important breakthrough. Disrupting sensor function causes accumulation of ceramides in the endoplasmic reticulum (ER) and their flow into mitochondria, triggering a mitochondrial pathway of apoptosis. While these results define the transfer of ER ceramides to mitochondria as a key determinant of cell fate, the molecular principles that govern ceramide trafficking at the ER-mitochondrial interface remain to be established.
In this project, I aim to unravel the transport mechanism by which ER ceramides can reach mitochondria to initiate apoptosis. I will conduct a chemical screen employing photoactivatable and clickable ceramide analogues to identify ceramide-binding proteins operating at the ER-mitochondrial interface. As complementary approach, I will conduct a functional screen to search for proteins required for delivering ER ceramides to mitochondria. This screen is based on the principal that blocking expression of such proteins would prevent cells with a disrupted ceramide sensor from committing suicide. Finally, I will evaluate newly-identified components of the ceramide trafficking machinery as targets for modulating drug-induced apoptosis in tumors.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- medical and health sciences clinical medicine oncology
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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.
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.
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.
FP7-PEOPLE-2011-IEF
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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.
Coordinator
49074 Osnabrueck
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.