Objective Bacteria have a range of immune mechanisms, but it is unclear why this diverse armamentarium evolved. The most important immune mechanisms are (1) Surface Modification (SM) (2) Abortive infection (Abi) (3) Restriction Modification (R-M) (4) CRISPR-Cas and (5) prokaryotic Argonaute (pAgo), all of which can occur as stand-alone mechanisms or in combination. The individual mechanisms differ in key aspects, such as their fitness costs (constitutive versus inducible), specificity (indiscriminate versus specific), the recipient of the benefits (individual versus group), the speed of de novo resistance evolution (rapid versus slow), and heritability of immunity. Here I will take a combined in vitro and in vivo approach to tease apart the variables that drive the evolution of these diverse stand-alone and integrated bacterial immune strategies in nature, and examine their associated co-evolutionary dynamics. I focus on three ecological variables that are consistently important in host-symbiont co-evolution: (1) force of infection (2) spatial structure (3) presence of mutualists (plasmids). First, I will perform in vitro manipulations using Pseudomonas aeruginosa PA14 variants that carry either single or multiple immune mechanisms. Next, I will sequence metagenomes, transcriptomes and viromes of microbial communities from environments that differ in ecological variables that are important in vitro, to examine their importance in vivo. Key ecological mechanisms identified in the first two parts of the project will be used to guide mesocosm experiments to experimentally confirm that these mechanisms are the drivers of the observed patterns of resistance and co-evolution in nature. Finally, I will share my data with mathematical biologists to generate theoretical models to predict and manipulate the evolution of bacterial immune mechanisms, which will facilitate tailored species protection in agriculture and industry. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesevolutionary biologymedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsmutation Keywords bacteria phage plasmid surface modification restriction modification CRISPR-Cas prokaryotic argonaute abortive infection Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-STG - ERC Starting Grant Call for proposal ERC-2016-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution THE UNIVERSITY OF EXETER Net EU contribution € 1 420 837,00 Address THE QUEEN'S DRIVE NORTHCOTE HOUSE EX4 4QJ Exeter United Kingdom See on map Region South West (England) Devon Devon CC 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 € 1 420 837,00 Beneficiaries (3) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE UNIVERSITY OF EXETER United Kingdom Net EU contribution € 1 420 837,00 Address THE QUEEN'S DRIVE NORTHCOTE HOUSE EX4 4QJ Exeter See on map Region South West (England) Devon Devon CC 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 € 1 420 837,00 UNIVERSITY OF OTAGO New Zealand Net EU contribution € 62 500,00 Address SAINT DAVID STREET 9054 Dunedin 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 Total cost € 62 500,00 THE UNIVERSITY OF LIVERPOOL United Kingdom Net EU contribution € 15 000,00 Address BROWNLOW HILL 765 FOUNDATION BUILDING L69 7ZX Liverpool 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 € 15 000,00