Post-doc position / Klaholz Lab
Development and application of high-resolution cryo-EM techniques to decipher the structure of key human translation complexes.
The Klaholz lab focuses on the molecular mechanism of translation by the human ribosome and its regulation. Using different sample preparation methods we have optimized the procedure of human ribosome purification for high-resolution studies (Khatter et al. Nature 2015; Natchiar et al. Nature 2017; Frechin et al. JSB 2022). Building on these achievements, we seek to recruit a highly motivated postdoctoral researcher that will use and develop classification methods for image processing and high-resolution structure refinements to obtain highly homogeneous cryo-EM structures of a key human translation complex. The project benefits from state-of-the art cryo electron microscopy instrumentation installed at the CBI/IGBMC which hosts French and European infrastructures.
Référence
IGBMC / POST DOC KLAHOLZ
Type de contrat
POST-DOC
Date de publication
05/06/2023
The successful candidate will work on a cutting-edge experimental research project to obtain a high-resolution structures involved in translation using the latest generation technology for cryo-EM data collection and image analysis. The project involves high-resolution cryo-EM data collection, using and further improving the latest developments in classification and refinements of large high-resolution datasets, atomic model building and structure interpretation.
The project will be carried out under the supervision of Ottilie von Loeffelholz in the friendly and supportive atmosphere of the Klaholz group, which has a strong track record in ribosome structure determination. The successful candidate will benefit from the thriving scientific environment of the CBI/IGBMC hosting a state-of-the-art cryo-EM facility including a Glacios equipped with a K2 camera, a G2 Titan Krios equipped with Volta phase plate, Gatan energy filter and Falcon III and K3 direct electron detectors as well as the recently installed G4 Titan Krios equipped with Volta phase plate, Selectris X energy filter and Falcon IVi direct electron detector. In addition the candidate will have access to the most recent equipment and services for biochemical sample preparation ranging from platforms for human cell cultures, molecular cloning, biophysical sample characterisation, genome-wide sequencing, and the possibilities to work with in vivo models. Highly performant in-house computational resources are available for the group as well as additional computational resources at the centre de calcul de l'Université de Strasbourg.
Informations complémentaires
The successful candidate will work on a cutting-edge experimental research project to obtain a high-resolution structures involved in translation using the latest generation technology for cryo-EM data collection and image analysis. The project involves high-resolution cryo-EM data collection, using and further improving the latest developments in classification and refinements of large high-resolution datasets, atomic model building and structure interpretation.
The project will be carried out under the supervision of Ottilie von Loeffelholz in the friendly and supportive atmosphere of the Klaholz group, which has a strong track record in ribosome structure determination. The successful candidate will benefit from the thriving scientific environment of the CBI/IGBMC hosting a state-of-the-art cryo-EM facility including a Glacios equipped with a K2 camera, a G2 Titan Krios equipped with Volta phase plate, Gatan energy filter and Falcon III and K3 direct electron detectors as well as the recently installed G4 Titan Krios equipped with Volta phase plate, Selectris X energy filter and Falcon IVi direct electron detector. In addition the candidate will have access to the most recent equipment and services for biochemical sample preparation ranging from platforms for human cell cultures, molecular cloning, biophysical sample characterisation, genome-wide sequencing, and the possibilities to work with in vivo models. Highly performant in-house computational resources are available for the group as well as additional computational resources at the centre de calcul de l'Université de Strasbourg.
Duration of the contract is for 1 year with the possibility for extension.
The salary will be based on experience following the institutes guidelines.
Please send your application including a statement describing research experience and expertise as well as future research interests, a curriculum vitae with publication list, date of availability, and at least two contact details for references (including phone number and email) to Ottilie von Loeffelholz (loeffelc@igbmc.fr) or Bruno Klaholz (klaholz@igbmc.fr). Informal enquires are very much welcome. Please, send your application before July 15, 2023, but note that applications will be processed continuously as they are received.
Selected Articles:
Fréchin, L., Holvec, S., von Loeffelholz, O., Hazemann, I., and Klaholz, B.P. (2022). High-resolution cryo-EM performance comparison of two latest-generation cryo electron microscopes on the human ribosome. J. Struct. Biol., 107905. 10.1016/j.jsb.2022.107905.
Khatter, H., Myasnikov, A.G., Natchiar, S.K., and Klaholz, B.P. (2015). Structure of the human 80S ribosome. Nature 520, 640–645. 10.1038/nature14427.
Natchiar, S.K., Myasnikov, A.G., Kratzat, H., Hazemann, I., and Klaholz, B.P. (2017). Visualization of chemical modifications in the human 80S ribosome structure. Nature 551, 472–477. 10.1038/nature24482.
von Loeffelholz, O., Natchiar, S.K., Djabeur, N., Myasnikov, A.G., Kratzat, H., Ménétret, J.-F., Hazemann, I., and Klaholz, B.P. (2017). Focused classification and refinement in high-resolution cryo-EM structural analysis of ribosome complexes. Curr. Opin. Struct. Biol. 46, 140–148. 10.1016/j.sbi.2017.07.007.
Bhaskar, V., Graff-Meyer, A., Schenk, A.D., Cavadini, S., von Loeffelholz, O., Natchiar, S.K., Artus-Revel, C.G., Hotz, H.-R., Bretones, G., Klaholz, B.P., et al. (2020). Dynamics of uS19 C-Terminal Tail during the Translation Elongation Cycle in Human Ribosomes. Cell Rep. 31, 107473. 10.1016/j.celrep.2020.03.037.
Afonine, P.V., Klaholz, B.P., Moriarty, N.W., Poon, B.K., Sobolev, O.V., Terwilliger, T.C., Adams, P.D., and Urzhumtsev, A. (2018). New tools for the analysis and validation of cryo-EM maps and atomic models. Acta Crystallogr. Sect. Struct. Biol. 74, 814–840. 10.1107/S2059798318009324.
Myasnikov, A.G., Kundhavai Natchiar, S., Nebout, M., Hazemann, I., Imbert, V., Khatter, H., Peyron, J.-F., and Klaholz, B.P. (2016). Structure–function insights reveal the human ribosome as a cancer target for antibiotics. Nat. Commun. 7. 10.1038/ncomms12856.
Gilles, A., Frechin, L., Natchiar, K., Biondani, G., Loeffelholz, O. von, Holvec, S., Malaval, J.-L., Winum, J.-Y., Klaholz, B.P., and Peyron, J.-F. (2020). Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies. Cells 9, 629. 10.3390/cells9030629.
Modalités de candidature
Please send your application including a statement describing research experience and expertise as well as future research interests, a curriculum vitae with publication list, date of availability, and at least two contact details for references (including phone number and email) to Ottilie von Loeffelholz (loeffelc@igbmc.fr) or Bruno Klaholz (klaholz@igbmc.fr). Informal enquires are very much welcome. Please, send your application before July 15, 2023, but note that applications will be processed continuously as they are received.
Associé à :
Profil
Duration of the contract is for 1 year with the possibility for extension.
The salary will be based on experience following the institutes guidelines.
Main research field : biological sciences / cryo electron microscopy (cryo-EM)
Offer Requirements : prior technical knowledge in either cryo electron microscopy, biochemistry of RNA or image processing of cryo-EM data is a plus, but is not essential as the group has well-established know-how in these techniques.
English: good level.
French speaking is NOT a requirement.
Eligibility criteria : The eligible candidate must hold a PhD for not longer than 2 years.