Objective
Small GTPases of the Ras superfamily, a major class of signalling proteins, control critical cellular functions, such as proliferation, differentiation, migration and trafficking. Their misregulation is associated with severe diseases, such as cancer or neurodegenerative diseases. More than 150 Ras-like GTPase are known, which are divided into four major subfamilies, each containing between 22 to 63 structurally related, but functionally distinct isoforms. A fundamental unresolved biological question in the field is the structure-based mechanism, which guides isoform specific functions. Recently, we provided new structural insight on how Ras operates in the context of the membrane. We showed that Ras adopts isoform specific orientations on the membrane, which in turn critically regulate Ras activity. These orientations are guided by a new switch III region and are stabilized by the amphipathic helix α4 and the membrane anchoring, C-terminal HyperVariable Region (HVR). Intriguingly, these structural elements vary from one isoform to another also in other subfamilies, suggesting that this mechanism is also operative in them. We will therefore study, whether this mechanism that involves helix α4 and the HVR also define isoforms of the Rho- and Rab-subfamily. In parallel, we will investigate the molecular mechanisms that are relevant for the overall membrane organisation of GTPases. This includes studies on the dynamics of the orientation, as well as on the mechanism of the formation of nanoscale assemblies (nanoclusters) of GTPases on the membrane. We expect that our results have the potential to substantially transform the current understanding of GTPase functioning and answer a long-standing fundamental biological question. Moreover, both mechanisms represent new, specific targets for pharmacological interventions.
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 biochemistry biomolecules proteins
- 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-2010-RG
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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
20500 ABO
Finland
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.