Objective
Cancer chemotherapeutic drugs, such as platinum agents, work by producing DNA damage that causes cell-cycle arrest and cell death. However, DNA repair pathways can enable tumour cells to survive DNA damage induced by chemotherapeutic treatments. Platinum resistance is a major clinical problem in cancer treatment and there is a considerable interest in inhibitors of DNA repair pathways, that can increase efficiency of chemotherapy, when administered together. An attractive target to circumvent platinum resistance is XPF/ERCC1 heterodimer. XPF/ERCC1 is a structure-specific endonuclease that cleaves double- to single-stranded DNA junctions, and its function is directly linked to repair of DNA cross-links induced by platinum agents. Here, we propose a multi-disciplinary methodology that combines structural studies by Nuclear Magnetic Resonance Spectroscopy with kinetic studies by Kinetic Capillary Electrophoresis to elucidate the mechanisms of XPF/ERCC1 function and modulate its activity for potential therapeutic benefit. Structural and molecular insights of DNA binding will be coupled with kinetic rates of DNA cleavage and enzyme/substrate interactions. The combined information will be used to develop XPF/ERCC1 inhibitors by in silico screening. Currently structure-kinetics relationship is not well explored in drug discovery, although the residence lifetime of a drug determines the duration of a pharmacological effect. The ability to combine structural and kinetic parameters in validating computational hits should identify compounds with desired pharmacological properties at early stages and facilitate faster optimization phase. The research proposed here is highly beneficial to public health, because it would allow to develop combination therapies for cancer treatment.
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 genetics DNA
- natural sciences chemical sciences inorganic chemistry transition metals
- natural sciences chemical sciences electrochemistry electrophoresis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences physical sciences optics spectroscopy
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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-2013-IIF
See other projects for this call
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
601 77 Brno
Czechia
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.