Objective
Angiogenesis, the growth of new blood vessels, is vital for tumour malignancy. Attempts to inhibit it by blocking VEGF has had limited success in the clinic with many patients innately resistant or acquiring resistance over time. Therefore, novel anti-angiogenic therapeutic strategies are required to improve overall efficacy and reduce resistance.
Novel work in the Carmeliet lab has highlighted the importance of the metabolic pathway in regulating the switch from a quiescent endothelial cell to a proliferative one. Little is known about how this angiogenic switch is regulated by metabolism and which metabolic pathways are even involved. One such pathway, the hexoasmine biosynthetic pathway (HBP) generates UDP-GlcNAc, necessary for post-translational modification of proteins via glycosylation. N-linked glycosylation can regulate growth factor receptor exposure on the surface and signaling, while O-linked glycosylation can rapidly alter the function and activity of nuclear and cytosolic proteins, alike phosphorylation.
Despite the important roles these modifications have, minimal research has been done into the role of glycosylation in angiogenesis. The proposal of this project is to investigate whether the HBP regulates angiogenesis via a specific “glycosylation switch”. In particular, using multi-disciplinary gene-discovery, pharmacological and genetic approaches in various animal models (zebrafish; mouse), I propose to investigate whether changes in nutrient supply regulate EC responses (quiescence versus proliferation) through selective HBP-mediated glycosylation of Flk1 or Notch and p53, and to explore the role and relevance of the HBP and key glycosylation pathways in EC quiescence / proliferation in vitro and (pathological) angiogenesis in vivo. The combination of genetic and translational studies might also open novel avenues to develop novel anti-angiogenic therapeutic strategies.
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
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
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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
9052 ZWIJNAARDE - GENT
Belgium
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.