Objective
Mycobacterium tuberculosis (Mtb) is the biggest killer among infectious diseases. Multi-drug resistant strains are widespread. New antibiotic strategies are desperately needed to combat the deadly pathogen. The genome sequence of Mtb revealed that Mtb encodes a high number (~20) of cytochromes P450 (P450s). These enzymes have roles in sterol, lipid and and polyketide metabolism in the cell. The recent determination of the genome sequence of the leprosy pathogen (M. leprae) indicates a much smaller number of proteins encoded, with only a single P450 remaining. The remaining P450 is likely to be essential for bacterial viability. Azole drugs which inhibit activity of P450 enzymes also exhibit potent anti-mycobacterial effects. This suggests that azoles may be useful new drugs against these deadly pathogens. The major objectives of this proposal are the systematic study of the sole M. leprae P450 and its homologue in M. tuberculosis. This will involve protein expression and purification of the P450s, and detailed kinetic, spectroscopic and structural analysis of these enzymes. The substrate selectivity will be determined by spectral titrations and lipid analysis, and activity will be reconstituted with expressed redox partners. Azoles interactions will be also be examined. Collectively, these studies will allow fundamental understanding of these P450s' properties and their potential as drug targets.
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.
- medical and health sciences health sciences infectious diseases
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug resistance
- 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.
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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
LE1 7RH LEICESTER
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.