Objective
The co-ordination and balance between cell proliferation and cell death is crucial for normal development of multicellular organisms as well as tissue-size homeostasis in the adult. Cancer occurs when this delicate balance is disrupted by mutations allowing the cell to proliferate and survive inappropriately.
Certain members of the Inhibitor of Apoptosis proteins (IAPs) protein family play a pivotal role in regulating caspase activation and activity. IAPs are evolutionarily conserved from insects to humans and suppress apoptosis induced by a large variety of cell death triggers. It is now clear that several human IAP homologues are deregulated in cancers, suggesting that IAP-mediated suppression of apoptosis contributes to tumour pathogenesis, progression, and resistance to drug treatment.
The mechanism of apoptosis is remarkably conserved, although with the expected greater complexity in mammals. In Drosophila cell survival is ensured by the IAP, DIAP1. Molecular and genetic data indicate that DIAP1 utilizes two independent mechanisms to regulate apoptosis. One relies upon the E3 ubiquitin protein ligase activity of DIAP1¿s own RING-finger while the other, the N-end rule, functions independently of this domain.
Despite that most IAPs identified in humans also contain a RING-finger motif and display E3 ubiquitin protein ligase activity, only little is known about how this activity of IAPs regulates apoptosis. The objective of the proposed research is to study the molecular mechanisms through which the ubiquitin system impacts on caspase regulation with specific focus on the role for IAP proteins. I will initially investigate how DIAP1 neutralizes effector caspases via the N-end rule mediated degradative pathway.
Moreover, I will study the importance of DIAP1¿s own E3 ubiquitin protein ligase activity in regulating apoptosis. Finally, I will expand my study to human IAPs and test whether my findings from Drosophila are evolutionarily conserved in humans.
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
- natural sciences biological sciences zoology entomology
- natural sciences biological sciences zoology mammalogy
- medical and health sciences basic medicine physiology homeostasis
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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-5
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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
United Kingdom
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.