Objective Wolbachia is a widespread, intracellular symbiont of arthropods and filarial nematodes, inducing reproductive distortions and antiviral protection in insects. Wolbachia is currently being deployed in disease vector control programs and is also a target in the treatment of lymphatic filariasis. Despite its prevalence, fascinating phenotypes, and applied importance, Wolbachia biology remains poorly explored, as it cannot be cultured or genetically manipulated. To date, antisense RNA and a transfection reagent that knock down Wolbachia gene expression have been deployed in cell culture, but the effect was modest and likely very transient. In order to achieve a robust and lasting antisense inhibition in Wolbachia, applicable in an in vivo system, I will utilize developments from drug delivery and gene manipulation in other members of the Rickettsiales. This will involve the use of nuclease resistant nucleic acid analogs, which can strongly inhibit transcripts for many days. This technology will be combined with attachment to different transporter molecules, known to deliver nucleic acids to other intracellular bacteria and parasites within host cells and organisms. I will then use this system to interrogate the genes putatively involved in host-microbe interactions in cell culture. I will focus on genes underlying symbiosis and those directly conferring the trait of antiviral resistance. The technology created will be widely applicable in studies of host-symbiont interactions, and in determining the mechanisms underlying the diverse phenotypes and symbioses observed. This project will thus both enable discovery science and allow better human disease prevention and treatment. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesbiological behavioural sciencesethologybiological interactionsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistancenatural sciencesbiological scienceszoologyinvertebrate zoologymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals 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-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator THE UNIVERSITY OF LIVERPOOL Net EU contribution € 183 454,80 Address BROWNLOW HILL 765 FOUNDATION BUILDING L69 7ZX Liverpool United Kingdom See on map Region North West (England) Merseyside Liverpool 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 Total cost € 183 454,80
