Objective
The rapid and ongoing resistance to all commonly used antibiotics by pathogenic bacteria urgently requires the development of a novel class of antibacterial drugs. This can be achieved by targeting essential processes in the cell. In this Project we propose to develop different strategies to target and inactivate the replicative DNA helicases, that are required in an essential process: the copy of the genetic material during the bacterial cell cycle. The inactivation of replicative DNA helicases is lethal to bacteria. The new knowledge of the structure of replicative DNA helicases and the proteins that interact with them will make possible the design of compounds that will target the helicases. The novelty of this approach is to target replicative DNA helicases which are not inhibited by currently available antibiotics.
The main effort of this project will be directed toward the analysis of the replicative helicases, their carriers and helicase inhibitors of Gram-negative (E. coli) and Grampositive (B. subtilis ) bacteria. Three converging strategies, explored by a multi-disciplinary team, will be used. First, the characterization of replicative DNA helicases and of known antihelicase proteins, paying special attention to the protein interfaces involved in the helicase-antihelicase interaction. Second, the search for and characterization of natural products and as well as newly designed ones able to inhibit the activity of replicative helicases in-vitro. Finally, we will develop in vivo screening methods to examine the efficiency of these compounds as antibiotics.
In summary, this project involves the functional and structural analysis of replicative DNA helicases and helicase-inhibitors, and the design of antimicrobial agents with antihelicase activity. The participation as a full partner of a Pharmaceutical Industry, Glaxo Wellcome, a leader in the field of new antimicrobials, guaranties the effective utilization and exploitation of the results obtained in this project.
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 microbiology bacteriology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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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
MADRID
Spain
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.