LS, Please see below for the project outline of a fully funded PhD project (3.5 years) in collaboration with Professor Bas Dutilh at the University of Jena. Start on February 2022. Please forward this to any students who may be interested and ask them to contact us. Investigating prokaryotic defence and bacteriophage anti-defence systems Project outline: Microbes and their viruses, known as bacteriophages, have co-evolved for billions of years. As a result of their co-evolution, microbes developed multiple lines of defence to withstand the predatory attacks of phages, and phages responded with multiple forms to overcome these barriers. Microbial defence systems such as restriction-modification (RM), abortive infection (Abi), and CRISPR-Cas have been known for years and used extensively to develop molecular biology and biotechnological tools. Recently, the field has bloomed with the discovery of tens of completely novel defence systems that microbes encode to protect from phage predation [Kronheim, Swarts, Goldfarb, Ofir, Cohen, Doron, Gao, Millman, Rousset]. With the realization that the arsenal of microbial defences is much more diverse than previously perceived, came exciting new questions, such as Do defence systems actively cooperate for better protection? Are there preferred combinations of defence systems? Furthermore, the discovery of new defence systems in microbes suggests that phages also carry anti-defence systems to help them overcome these prokaryotic barriers. This may help reconcile the number of proteins of unknown function in phage genomes that have been found to be dispensable for infection of permissible hosts [Miller, Pires]. This raises important additional questions, such as Which mechanisms do phages employ to escape the new systems? How do phages protect against such large diversity of defence mechanisms while maintaining a compact genome? References: - Kronheim, S. et al. A chemical defence against phage infection. Nature 564, 283-286, doi:10.1038/s41586-018-0767-x (2018). - Swarts, D. C. et al. DNA-guided DNA interference by a prokaryotic Argonaute. Nature 507, 258-261, doi:10.1038/nature12971 (2014). - Goldfarb, T. et al. BREX is a novel phage resistance system widespread in microbial genomes. The EMBO journal 34, 169-183, doi:10.15252/embj.201489455 (2015). - Ofir, G. et al. DISARM is a widespread bacterial defence system with broad anti-phage activities. Nature Microbiology 3, 90-98, doi:10.1038/s41564-017-0051-0 (2018). - Cohen, D. et al. Cyclic GMP–AMP signalling protects bacteria against viral infection. Nature 574, 691-695, doi:10.1038/s41586-019-1605-5 (2019). - Doron, S. et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359, eaar4120, doi:10.1126/science.aar4120 (2018). - Gao, L. et al. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369, 1077-1084, doi:10.1126/science.aba0372 (2020). - Millman, A. et al. Bacterial Retrons Function In Anti-Phage Defense. Cell 183, 1551-1561.e1512, doi:10.1016/j.cell.2020.09.065 (2020). - Rousset, F., Dowding, J., Bernheim, A., Rocha, E. P. C. & Bikard, D. Prophage-encoded hotspots of bacterial immune systems. bioRxiv, 2021.2001.2021.427644, doi:10.1101/2021.01.21.427644 (2021). - Miller, E. S. et al. Bacteriophage T4 genome. Microbiol Mol Biol Rev 67, 86-156, doi:10.1128/mmbr.67.1.86-156.2003 (2003). - Pires, D. P. et al. Designing P. aeruginosa synthetic phages with reduced genomes. Scientific Reports 11, 2164, doi:10.1038/s41598-021-81580-2 (2021). Franklin Nóbrega, PhD Lecturer in Microbiology Microbial Interactions Lab University of Southampton Life Sciences Building 85 Highfield Campus Southampton SO17 1BJ UK fnobregalab.org<http://fnobregalab.org> Prof. Dr. Bas E. Dutilh<https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Ftbb.bio.uu.nl%2Fdutilh&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154133808%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=qj1E%2BkZNnJdicwPKEVbJPXcMk0YQ9%2Blt3CdANCzl8%2BU%3D&reserved=0> Viral Ecology and Omics Group | Metagenomics Group Microverse Cluster<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fmicroverse-cluster.de%2Fen%2F&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154133808%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=qqIlCsCIbx%2Bm3KsWkCg2JkB%2BPy2qQ114ZgP%2FUb91zlE%3D&reserved=0> | Theoretical Biology and Bioinformatics<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftbb.bio.uu.nl%2F&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154143764%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=V6WpsUAwOyYZQ%2FsqmEyzmOtpKaG3hxDll6kHqReakwk%3D&reserved=0> European Virus Bioinformatics Centre<https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fevbc.uni-jena.de%2F&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154143764%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=Zye0YgDcU7SVb5lZzrdSZ9MFNZoX24DsxXm7IIxgccg%3D&reserved=0> | Utrecht Bioinformatics Center<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fubc.uu.nl%2F&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154153736%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=c1jVz2iGtiZBfoHZ1MEZIcAuZS6nzcNiN1AfzhkeVcw%3D&reserved=0> Friedrich Schiller University Jena<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.uni-jena.de%2Fen%2F&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154153736%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=IUbDiK41fygoufETYVPVT5iU8jaSe64ljB4KcQgG2u0%3D&reserved=0> | Utrecht University<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.uu.nl%2F&data=04%7C01%7CF.Nobrega%40soton.ac.uk%7C1c20561b06c945e09ea508d9afdd09d9%7C4a5378f929f44d3ebe89669d03ada9d8%7C0%7C0%7C637734186154163676%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=vxqBbigAlFCh5gHejWb2eS2IN3aDt0ED3ORTYTm%2BhaA%3D&reserved=0>