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Call for postdoctoral applicants in chemical biology
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Job description
Offer DescriptionCall for postdoctoral applicants in chemical biologyAre you a skilled and highly motivated postdoc with an expertise and track record in chemical biology and/or synthetic chemistry?Then apply to a 2-year postdoctoral fellowship to join the lab and work on:Supramolecular polymers as a platform for the dynamic assembly of a transmembrane kinase.Context – Cellular stress induced by the abnormal accumulation of improperly folded proteins in the endoplasmic reticulum (ER) is emerging as a major actor in disease development and an appealing actionable target. ER stress levels are under constant surveillance by the unfolded protein response (UPR), a major adaptive mechanism that lies at the core of cellular homeostasis and is responsible for cellular life-or-death decisions. The Inositol-requiring enzyme 1 (IRE1), the most evolutionary conserved UPR transducer, is an ER-resident transmembrane protein with a cytosolic dual kinase/RNase activity controlling pro-survival or pro-death signals. Yet, despite
20 years of investigations, the precise molecular mechanisms by which IRE1 is activated and exerts its catalytic and scaffolding functions still remain unclear and a subject of debate.Mission – This project is part of the Agence Nationale de la Recherche (ANR)-funded INSPIRE program, which aims at deciphering the molecular mechanisms of IRE1 through a unique and novel prism at the interface of chemical biology, supramolecular chemistry and structural biology. More specifically, you will focus on creating supramolecular polymers to use as a dynamic, one-dimensional, synthetic mimic of the endoplasmic reticulum (ER) membrane to characterize how IRE1 dynamically assemble under set conditions.This approach will enable you to:1 – Recreate low to high ER stress conditions for the systematic study of tailor-made protein complexes dynamic assembly and enzymatic activities within the supramolecular wire.2 – Investigate the stress sensing mechanism(s) by the luminal domain of this important kinase in charge of restoring protein homeostasis under ER stress (i.e. accumulation of misfolded protein).3 – Obtain structural information on these different complexes by microscopy & CryoEM.Main activities –
- Synthetic chemistry (plan and carry out syntheses of the supramolecular polymers building blocks)
- Protein expression in prokaryotic (bacteria) and eukaryotic (insect and human) cells.
- Protein engineering, bioconjugation, purification (affinity & SEC).
- Structural characterization of protein-supramolecular polymer conjugates (CryoEM).
- Functional and biophysical characterization in vitro of enzymatic activities (kinase & RNase), substrate specificity (RT-qPCR), protein-protein interactions (biophysical assays).
The candidate must possess a strong scientific rigor and a keen interest and motivation for interdisciplinary projects, along with autonomy, critical thinking and the ability to work as part of a team.Environment – The INSERM U1242 laboratory ( ) is a translational research structure bringing together biologists, chemists and clinicians to better understand oncogenesis in brain and gynecological cancers. By associating biologists working on cancer stress signaling pathways, chemists developing molecular tools and cancer clinicians, the laboratory aims at deciphering how tumor cells cope with stresses to resist to death and how they could be sensitized to treatments. The candidate will join an exciting and multidisciplinary scientific environment with on-site access to cutting-edge facilities in chemistry, biochemistry, biophysics, molecular biology, cell biology and structural biology.The INSERM U1242 laboratory Is affiliated to the Université of Rennes, a top French university that offers a dynamic and lively international campus with an ideal location less than 2 hours from Paris and 1 hour from Saint Malo and the beautiful Britany coast.National and international collaborations
- Pr. François-Hugues Porée, synthetic chemistry, Université de Rennes, France.
- Dr Pierre Maisonneuve, structural biology, Université de Bordeaux, France.
- Pr. Luc Brunsveld, synthetic platforms, Eindhoven University of Technology, Netherlands.
- Pr. Leif A. Eriksson, molecular modeling of protein complexes, University of Gothenburg, Sweden.
Fellowship & Eligibility criteria – BIENVENÜE is an international post-doctoral fellowship program aiming at attracting talented scientists to develop their two-year project in Breton laboratories. See full details here: . To be eligible, the applicant must have spent at least 18 months abroad between the 1st of May 2021and the start of the project and the hosting lab must provide co-funding of at least 25% (already acquired).Application deadline 27th May 2024To apply, send CV, cover letter, and at least one contact likely to provide a recommendation to:Dr. Xavier Guillory –Recent references from the group1. Mahdizadeh, S. J.; Grandén, J.; Pelizzari-Raymundo, D.; Guillory, X.; Carlesso, A.; Chevet, E.; Eriksson, L. A. Different Binding Modalities of Quercetin to Inositol-Requiring Enzyme 1 of S. Cerevisiae and Human Lead to Opposite Regulation. Commun. Chem.2024, 7 (1), 1-12. .2. Pelizzari-Raymundo, D.; Doultsinos, D.; Pineau, R.; Sauzay, C.; Koutsandreas, T.; Langlais, T.; Carlesso, A.; Gkotsi, E.; Negroni, L.; Avril, T.; Chatziioannou, A.; Chevet, E.; Eriksson, L. A.; Guillory, X. A Novel IRE1 Kinase Inhibitor for Adjuvant Glioblastoma Treatment. iScience2023, 106687. .3. Obacz, J.; Archambeau, J.; Lafont, E.; Nivet, M.; Martin, S.; Aubry, M.; Voutetakis, K.; Pineau, R.; Boniface, R.; Sicari, D.; Pelizzari-Raymundo, D.; Ghukasyan, G.; McGrath, E.; Vlachavas, E.-I.; Le Gallo, M.; Le Reste, P. J.; Barroso, K.; Fainsod-Levi, T.; Obiedat, A.; Granot, Z.; Tirosh, B.; Samal, J.; Pandit, A.; Négroni, L.; Soriano, N.; Monnier, A.; Mosser, J.; Chatziioannou, A.; Quillien, V.; Chevet, E.; Avril, T. IRE1 Endoribonuclease Signaling Promotes Myeloid Cell Infiltration in Glioblastoma. Neuro-Oncology2023, noad256. .4. Langlais, T.; Pelizzari-Raymundo, D.; Mahdizadeh, S. J.; Gouault, N.; Carreaux, F.; Chevet, E.; Eriksson, L. A.; Guillory, X. Structural and Molecular Bases to IRE1 Activity Modulation. Biochemical Journal2021, 478 (15), 2953-2975. .RequirementsResearch Field Chemistry Education Level PhD or equivalentLanguages ENGLISH Level GoodAdditional InformationBenefitsStarting at ~2900 euros brut/month + benefitsEligibility criteriaThe applicant must have spent at least 18 months abroad between the 1st of May 2021and the start of the project and the hosting lab must provide co-funding of at least 25% (already acquired).Work Location(s)Number of offers available 1 Company/Institute Inserm U1242 Country France State/Province Ille-et-Vilaine City Rennes Postal Code 35000 Street Avenue Bataille Flandres-Dunkerque GeofieldWhere to apply E-mail[email protected]Contact CityNANTES WebsiteStreet24 Boulevard Vincent Gâche Postal Code44200STATUS: EXPIRED
Expected salary
Location
Rennes, Ille-et-Vilaine
Job date
Sun, 14 Apr 2024 04:03:51 GMT
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