Objective
The Patched-Hedgehog signalling pathway is considered to be instrumental for normal developmental patterns but is also implicated in a number of cancer transformation processes that were recently found to include, basal cell carcinomas, but also pancreatic, digestive track and lung cancers. Studies, mainly in Drosophila, have allowed the dissection of the major components of this signal transduction system, that is the Hedgehog receptor Patched, the membrane signalling protein Smoothened, the intracellular transducers Fused, Suppressor of Fused and Costal 2 and the transcription factor Cubitus Interruptus.
However careful analysis of this pathway in mammalian systems revealed a higher complexity than Drosophila, and this is exemplified by the duplication or triplication of some of these components. Humans, for example, have three Hedgehog ligands, two Patched receptors and three Cubitus Interruptus homologs. Moreover the process of alternative pre-mRNA splicing has revealed additional component comple xity. For example GLI1, a Cubitus Interruptus human homolog, was found to express three different mRNAs, each with a unique combination of 5- untranslated exons that confer distinct capacities in translational efficiency.
The focus of this proposal is to expand on recent findings from our laboratory that suggest widespread splicing variation in components of this pathway. Specifically a Patched 1 variant that includes a novel first exon has been identified. Expression of this variant is up regulated by Hedgehog signalling and its functional properties are characterized by a pathway inhibitory capacity (Shimokawa et al, FEBS Lett. 578, 157-162, 2004). Additionally analysis of GLI1 expression revealed further complexity in the 5- exons, which is highly likely t o have functional implications. We would like to continue these studies and address whether targeting specific variants may represent a means to achieve a highly selective disease therapy.
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 computer and information sciences databases
- medical and health sciences clinical medicine oncology lung cancer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology skin cancer basal cells
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Programme(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-7
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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.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
STOCKHOLM
Sweden
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.