Objective
The goal of the current proposal is to define the mechanisms that control phosphatidylinositol (PtdIns) biosynthesis. PtdIns is a structural component of the membrane and a precursor to signalling molecules. Its biosynthetic pathway utilizes phosphatidic ac id (PtdOH) and cytidylyldiphosphodiacylglycerol (CDP-DAG). There are two mammalian genes encoding CDP-DAG synthetases (CDS1 and CDS2). In the current proposal we will test whether one CDS isoform is involved in de novo PtdIns formation whereas the other participates in the turnover of PtdIns after agonist-induced stimulation of phospholipase C. There are strong computational evidence for CDS1 and CDS2 phosphorylation, and we propose to develop isoform specific antibodies to characterize the post-translation al modifications as well as the sub-cellular distribution of the two isoforms. The second goal is to identify the enzyme(s) that regulate the distribution of PtdOH between the CDP-DAG and diacylglycerol.
Our alternative hypothesis suggests that PtdIns bio-synthesis is regulated by the supply of PtdOH, the substrate of CDS. Magnesium-dependent phosphatidate phosphohydrolase (PAP1) is the enzyme involved in the de novo pathway of PtdOH utilization. The gene(s) coding for PAP1 enzyme(s) have not been characterized. We used a bio-informatics approach to identify two novel genes as candidates for PAP1 and we propose to characterize their biochemical activities and cellular functions as well as their involvement in PtdIns biosynthesis. Propranolol and bromoenol lactone have been previously identified as PAP1 inhibitors and additional micro-array experiments are proposed to characterize the transcriptional response to them, which may lead to the identification of their target PAP1 gene(s). The results of these studies will identify novel players in PtdIns biosynthesis, advance our understanding of the mechanisms that govern mammalian PtdIns metabolism and may lead to the development of novel therapeutics.
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.
- engineering and technology materials engineering amorphous solids amorphous semiconductors
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences genetics genomes
- 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.
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.
FP6-2002-MOBILITY-12
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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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
ATHENS
Greece
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.