Project description DEENESFRITPL Novel molecular targets against Mycobacteria Antimicrobial resistance is increasing in prevalence affecting various bacteria, including Mycobacterium tuberculosis. Profoundly, this necessitates the development of novel effective drugs. The project deCrYPtion, funded by the EU, proposes to target the cytochrome P450 (CYP) family of proteins as a treatment strategy. The main goal is to provide physiological information on a number of CYPs that have yet to be functionally characterised. Scientists will analyse the CYPs encoded by Mycobacterium species and link their function to specific biological pathways. deCrYPtion results will lead to the identification of novel drug targets against the Mycobacterium genus. Show the project objective Hide the project objective Objective More than 190 species belong to the Mycobacterium genus. Among those, several are pathogenic to human and animals. The high number of human lives lost and the economic consequences of livestock infection are important incentives in the control and eradication of the responsible organisms. M. tuberculosis, one of the causative agents of tuberculosis (TB), is the most problematic representative: in 2016, 1.7 million deaths worldwide have been attributed to TB. Like for other infectious organisms, antibiotic resistances have appeared in Mycobacterium. Thus, there is a fundamental need to develop new antimycobacterial drugs. The inhibition of enzymes belonging to the Cytochrome P450 (CYP) protein family has been shown to suppresses the growth of several Mycobacterium species, making CYPs targets for drug development. Unfortunately, most CYPs are considered orphan: proteins for which no physiological function is known. The deCrYPtion action aims to define the physiological function of a selected set of mycobacterial CYPs. It will prove determinant in the development of new antibiotics. I will perform a large-scale comparative genomics analysis of the CYPs encoded by Mycobacterium species, in order to define orthologous groups and identify, for each, conserved partners and pathway context. This approach is extremely powerful (even if not frequently used) and allow to propose physiological functions, based on the information obtained. Specific CYPs to be characterized will be selected based on a set of stringent considerations, including their potential as drug targets. A preliminary analysis illustrates the approach that will be used. A combination of complementary biochemical, genetics and physiological experiments will be performed to validate the hypotheses generated. deCrYPtion will be undertaken within the Centre for Cytochrome P450 Biodiversity, under the supervision of Prof Steven Kelly, at Swansea University (Wales, United Kingdom). Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencesgeneticsmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator SWANSEA UNIVERSITY Net EU contribution € 212 933,76 Address Singleton park SA2 8PP Swansea United Kingdom See on map Region Wales West Wales and The Valleys Swansea Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
