Objective
Flap endonuclease 1 (FEN1) catalyzes the removal of 5’-flap structures generated by strand-displacement synthesis during lagging-strand DNA synthesis and long-patch base excision repair. Homozygous knockout of FEN1 in mice is embryonically lethal, whereas haploinsufficiency or catalytic deficiency due to mutation leads to rapid tumor progression, thereby illustrating the importance of FEN1 to genome stability. Despite its critical role in DNA replication and repair, a detailed mechanistic understanding of how FEN1 enzymes achieve substrate specificity and scissile phosphate selectivity without sequence information is still poorly understood. Detailed kinetic studies from the laboratory of Dr. Jane Grasby suggest that a concerted enzyme-substrate conformational change is essential to create a cleavage-competent FEN1-substrate complex. Testing such a hypothesis requires an arsenal of molecular, chemical, kinetic, biophysical, and structural techniques. Although such studies are already underway in the Grasby laboratory, one powerful tool missing from the ‘Grasby arsenal’ that would greatly compliment her current work is NMR relaxation dispersion (RD) experiments, which can identify at the atomic level sites in and quantify the time scale of motion. Combining NMR-RD data with biophysical data routinely obtained in her lab would allow for direct correlations between observed rates of reaction and conformation exchange processes occurring in the protein and substrate as has been done for RNase A. Although the University of Sheffield has the instrumentation and protein NMR expertise of Dr. Jeremy Waltho, the presence of a researcher experienced in both NMR and enzymology would increase the chances for success of and greatly expedite the completion of the project. As a graduate student and postdoctoral fellow, the coordinator gained experience in protein-nucleic acid NMR and enzymology, respectively, and thus, is well suited to this task.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences catalysis
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2009-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
S10 2TN SHEFFIELD
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.