Objective Secretion systems are evolved machineries enabling bacteria to deliver toxins and virulence factors, called effectors, into target cells to enable the onset of infectious diseases. Uncovering these effectors is essential for the understanding of bacterial pathogenesis and the establishment of appropriate therapeutic strategies to tackle infectious diseases. The recently identified Type Six Secretion System (T6SS) is conserved in environmental and pathogenic Gram-negative bacteria. The T6SS is an organelle structurally akin to an intracellular and membrane-bound contractile phage tail used for the delivery of toxins into prokaryotic and eukaryotic target cells. The importance of this system in the context of infection is highlighted by its ability to not only target eukaryotic cells during bacterial infection, but additionally to target other bacteria co-infecting mammalian and plant hosts. Despite the recent advances made in understanding the mechanisms underlying the T6SS dynamic, very little is known about the T6SS effectors repertoire used by life-threatening pathogens, such as Burkholderia pseudomallei, and for which, vaccine strategies are currently unavailable. In the proposed research, a combination of high-throughput and cross-disciplinary technologies will be used to uncover and characterise novel T6SS effectors in B. thailandensis, a surrogate organism closely related to B. pseudomallei. This will 1) identify new T6SS effectors targeting eukaryotic cells, using a reporter-based transposon screening and 2) identify novel T6SS toxins targeting prokaryotic cells, using a genome-wide saturation mutagenesis strategy. The outcomes of the proposed research will identify the key cellular stages hijacked by the T6SS during the infection of a host, while exposing potential new bacterial targets exploitable for the development of novel antimicrobial strategies. Fields of science medical and health scienceshealth sciencestropical medicinenatural sciencesbiological sciencesmicrobiologybacteriologymedical and health scienceshealth sciencesinfectious diseasesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical 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-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-GF - Global Fellowships Coordinator LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER Net EU contribution € 276 107,40 Address Keppel street WC1E 7HT London United Kingdom See on map Region London Inner London — West Camden and City of London 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 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. UNIVERSITY OF MELBOURNE Australia Net EU contribution € 0,00 Address Parkvilleoffice of the vice chancellor 3010 Melbourne See on map 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 € 178 380,00
