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lixuyang1新虫 (初入文坛)
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哥本哈根大学生物系招2023年CSC博士研究生
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PhD project – Characterization of anti-defense genes of archaeal viruses Introduction The co-existence of selfish mobile genetic elements (MGEs, e.g. viruses and plasmids) with their prokaryotic hosts has resulted in a large and diverse array of defense mechanisms that protect cells against these elements, with over 50 prokaryotic defense systems described up to date (1-3). Expectedly, MGEs have in turn developed ways to inhibit cellular defenses, the so-called anti-defense elements, which tend to cluster within anti-defense islands in the viral genomes (4). CRISPR-Cas systems are the only example of adaptive immunity in prokaryotes and, in a nutshell, work by mediating the RNA-guided, sequence-specific recognition and degradation of complementary invading nucleic acids (5). One mechanism by which MGEs can escape the action of CRISPR-Cas systems is by the action of anti-CRISPR (acr) proteins. The majority of the members of the archaea (a total of 85%) contain CRISPR-Cas systems, which contrasts markedly with the 42% prevalence in bacteria (5). Accordingly, we expect the majority of anti-defense viral elements to be acrs. However, only three anti-CRISPRs have been described in archaeal viruses (6-8), whereas 181 acr families have been characterized in bacteriophages. Project Previous work in our group identified and characterized the first acrs against subtypes I-D (6), III-B (7) and I-A (unpublished) CRISPR-Cas systems, and a viral inhibitor of an abortive system (unpublished). Using bioinformatics we have additionally identified 30 putative anti-defense genes in crenarchaeal viruses (unpublished) through the identification of anti-defense islands in their genomes, and the aim of this project is to investigate the function, mechanism of action and regulation of the expression of these anti-defense genes. We envisage to use approaches that include molecular biology and biochemical assays, protein expression and purification, genetic manipulation of Sulfolobus and/or its viruses and bioinformatics. We use the hyperthermophilic crenarchaeon Sulfolobus islandicus as our research model because it is amenable to genetic manipulation and can be infected by members of different families of archaeal viruses. Given that prokaryote defense systems (particularly CRISPR-Cas) have great biotechnological potential and have been used in the development of several genome-engineering tools, the results of this project have the potential to serve as regulators of these tools and for the understanding of antiviral resistance and virus-host interactions in the archaea domain. Profile of applicants Applicants should hold a Master’s degree in any field of Life Sciences. A background in prokaryote molecular biology, cell biology, biochemistry or bioinformatics is preferred, but not mandatory. Medium to high proficiency in English is required. Environment You will join the Microbial Immunity group (https://www1.bio.ku.dk/english/research/fg/peng/ ) headed by Professor Xu Peng at the University of Copenhagen, Denmark. We are an international group investigating diverse aspects of archaeal biology, with particular focus in virus-host interactions within the hyperthermophilic crenarchaea and a strong background in microbial immunity. The group has experience with archaeal and bacterial CRISPR-Cas systems and its viral counterparts, the anti-CRISPRs and has established approaches to genetically manipulate Sulfolobus islandicus and its viruses. Other than Sulfolobus, the lab has experience with CRISPR-Cas systems of gram-positive, acidophilic bacteria (e.g. Lactobacillus, Streptococcus). As a PhD student at our group, you will be exposed to different topics related to microbial immunity and gain ample knowledge about archaeal viruses and virus-host interactions while participating in frontier research projects. Additionally, the University of Copenhagen is among the top 30 universities internationally with a strong PhD student network. Applications Aspirants that had their visa application rejected by the U.S.A. immigration are encouraged to submit an application with us. Applications should be addressed to peng@bio.ku.dk and include a full CV and motivation statement. Additional questions about the project or the position can be addressed to Li Xuyang (xuyang.li@bio.ku.dk) or Laura Martínez Alvarez (laura.martinez@bio.ku.dk). References 1. Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A, Keren M, Amitai G, Sorek R. 2018. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359:eaar4120. 2. Gao L, Altae-Tran H, Böhning F, Makarova KS, Segel M, Schmid-Burgk JL, Koob J, Wolf YI, Koonin EV, Zhang F. 2020. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369:1077–1084. 3. Pawluk A, Davidson AR, Maxwell KL. 2018. Anti-CRISPR: discovery, mechanism and function. Nat Rev Microbiol 16:12–17. 4. Makarova KS, Wolf YI, Iranzo J, Shmakov SA, Alkhnbashi OS, Brouns SJJ, Charpentier E, Cheng D, Haft DH, Horvath P, Moineau S, Mojica FJM, Scott D, Shah SA, Siksnys V, Terns MP, Venclovas Č, White MF, Yakunin AF, Yan W, Zhang F, Garrett RA, Backofen R, van der Oost J, Barrangou R, Koonin EV. 2020. Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants. 2. Nat Rev Microbiol 18:67–83. 5. He F, Bhoobalan-Chitty Y, Van LB, Kjeldsen AL, Dedola M, Makarova KS, Koonin EV, Brodersen DE, Peng X. 2018. Anti-CRISPR proteins encoded by archaeal lytic viruses inhibit subtype I-D immunity. Nat Microbiol 3:461–469. 6. Bhoobalan-Chitty Y, Johansen TB, Di Cianni N, Peng X. 2019. Inhibition of Type III CRISPR-Cas Immunity by an Archaeal Virus-Encoded Anti-CRISPR Protein. Cell 179:448-458.e11. 7. Athukoralage JS, McMahon SA, Zhang C, Grüschow S, Graham S, Krupovic M, Whitaker RJ, Gloster TM, White MF. 2020. An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity. Nature 577:572–575. |
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