We are looking for a PhD student (f/m) starting on 1 November 2022 or on 1 January 2023 in our team at the Institut de Biologie Structurale (IBS) in Grenoble, France working on the
Structure of the vaccinia virus DNA replication machinery in complex with DNA substrates by single-particle cryo-electron microscopy
With the recent spread of monkeypox infections, poxviruses got into the headlines. Our team works on the elucidation of structure and function of the poxvirus DNA replication machinery, now mainly by single-particle cryo-electron microscopy. The DNA replication of vaccinia virus, a safe model system, involves the DNA polymerase holoenzyme complex E9-A20-D4, furthermore the hexameric helicase-primase D5. The aim is to determine structures of these assemblies by cryo-EM with bound DNA substrates, nucleotides, inhibitors and nucleotide analogues in order to stabilize different functional states for the understanding of poxvirus DNA replication. The project builds on the team’s experiences in the structure determination and biophysical characterization of the partners and their domains, our recent results on the cryo-EM of the helicase domain of D5 and first results by cryo-EM on the holoenzyme.
The candidate should be computer literate and have some experience in the use of Linux. Knowledge of relevant software packages used for cryo-EM will be an asset. Furthermore, a sound background in biochemistry, physics or biophysics is required as the project comprises multiple methods: protein production in the baculovirus-insect cell system; protein purification by affinity chromatography; sample preparation for cryo-EM. structure calculations for single-particle cryo-EM on a Linux computing cluster; analysis and visualization of protein structures.
The successful candidate will work in a small team interested in poxvirus DNA replication directed by Prof. Wim Burmeister within the « Viral Replication Machines group ». Cryo-EM and computing facilities are available on the research campus, which is shared with international institutes: the EMBL Grenoble outstation, the ESRF synchrotron and the ILL research reactor. Working languages of the institute are English and French. Grenoble is a mid-size town with an international atmosphere located in the middle of the French Alps. The net salary is about 1750 €/month (~2000 € gross salary),
In order to candidate please send a CV, a letter of motivation and a copy of the Master diploma with marks to wim.burmeis...@ibs.fr before 30 September, 2022.
Bibliography
Tarbouriech N, Ducournau C, Hutin S, Mas PJ, Man P, Forest E, Hart DJ, Peyrefitte CN, Burmeister WP & Iseni F. The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding. Nat Commun. 2017;8: 1455.* doi:10.1038/s41467-017-01542-z.
Bersch B, Tarbouriech N, Burmeister WP, Iseni F. Solution structure of the C-terminal domain of A20, the missing brick for the characterization of the interface between vaccinia virus DNA polymerase and its processivity factor. J Mol Biol. 2021; 167009.* doi:10.1016/j.jmb.2021.167009.
Hutin, S., Ling, W.L., Tarbouriech, N., Schoehn, G, Grimm, G., Fischer, U. & Burmeister, W.P. The vaccinia virus DNA helicase structure from combined single-particle cryo-electron microscopy and AlphaFold2 prediction. Viruses. In press.
Wim Burmeister
Professeur
Institut
de Biologie Structurale (IBS) CIBB
71
avenue des Martyrs / CS 20192
E-mail: wim.burmeis...@ibs.fr
Tel: +33 (0) 457 42 87 41 Fax: +33 (0) 476 20 94 00
Changement climatique : «Les autres combats n’ont aucun sens si celui-là est perdu» (Aurélien Barrau)
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