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Postdoc position in molecular biology, biochemistry and structural biology

Our group at the IGBMC in Illkirch (France) has an open Postdoc position. We are looking for a passionate postdoctoral fellow who is eager to combine molecular biology, biochemistry with cryo-electron microscopy to investigate mechanisms of transcription regulation by the glucocorticoid receptor. We are an international team at an interdisciplinary research center with excellent in-house access to state-of-the-art EM infrastructure, scientific services and technological platforms.

Référence
IGBMC / POST DOC A.H

Type de contrat
POST-DOC

Date de publication
09/11/2022

About us

The Hamiche group is part of the Institute of Genetics and Cellular and Molecular Biology (IGBMC), the largest French academic research unit, under the supervision of Inserm, CNRS and the University of Strasbourg. The institute develops interdisciplinary research at the interface of biology, biochemistry, structural biology, physics and medicine, hosts state-of-the art scientific services and technological platforms, and attracts students from around the world by offering high-level education in biomedical sciences. IGBMC is located at the “Parc d’Innovation d’Illkirch”, an exceptional scientific, academic and industrial environment next to Strasbourg.

Our laboratory has an international reputation in chromatin biology, epigenetics, histone variants and regulation of gene expression by transcription factors, including nuclear receptors. The team is working on the isolation and purification of various macromolecular complexes to decipher their functional role using protein and DNA biochemistry, molecular and cell biology techniques, X-ray crystallography and single particle cryo-electron microscopy. Within the Hamiche team, Dr. Isabelle Billas is a project leader with expertise in biochemistry, biophysics and structural biology and she has been leading the research work focusing to the understanding of the mechanisms of transcription regulation by steroid nuclear receptors. She will be supervising the GR project and will benefit from the multidisciplinary environment of the group. 

The Hamiche group profits from funding by different national and international institutions and caritative associations. We have access to an excellent mammalian and insect cell culture facility in house and state-of-the-art fluorescence, mass spectrometry, and genomics. The IGBMC that hosts one of node of the French Infrastructure for Integrated Structural Biology (FRISBI frisbi.eu) , a part of the European distributed infrastructure Instruct EM (http://www.structuralbiology.eu) entertains strong structural core facilities including protein production, crystallography, biophysics, high performance computing and state-of-the art electron microscopy instrumentation (2 Titan Krios and one Galcios microscopes). You will thus join a collaborative and international work environment.

 

Project description

This project entails an exciting combination of molecular biology, biochemistry, and structural biology, in particular single particle cryo-EM, to investigate transcription regulation by the glucocorticoid receptor. GR plays an important role in immune and stress response and is the main target of synthetic compounds widely prescribed for chronic inflammatory and autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis and asthma. However, chronic use of these compounds can result in important tissue-specific side effect, as they increase gluconeogenesis and inhibit insulin action, therefore leading to an increased risk of type-2 diabetes, cause osteoporosis as well as muscle weakness and atrophy. However, molecular mechanisms of glucocorticoid actions through GR are still poorly characterized.

This project aims to identify macromolecular complexes associated with GR in skeletal muscles and other target tissues, to purify and reconstitute complexes for functional physico-chemical studies and for structural characterization using cryo EM. Prior experience with eukaryotic cell culture, biochemistry and protein purification is therefore required. Experience with cryo EM is desired.

Informations complémentaires

Selected publications of the team:

  1. Sandra Postel, Lisa Wissler, Carina A. Johansson, Anders Gunnarsson, Euan Gordon, Barry Collins, Marie Castaldo, Christian Köhler, David Öling, Patrik Johansson, Linda Fröderberg Roth, Brice Beinsteiner, Ian Dainty, Stephen Delaney, Bruno P. Klaholz, Isabelle M.L. Billas, Karl Edman (2022).“Quaternary GR structure highlights allosteric interdomain communication”, Nat. Struct. Mol. Biol., in press.
  2. Beinsteiner, B., G. V. Markov, M. Bourguet, A. G. McEwen, S. Erb, A. K. M. Patel, F. Z. El Khaloufi El Khaddar, C. Lecroisey, G. Holzer, K. Essabri, I. Hazemann, A. Hamiche, S. Cianférani, D. Moras, V. Laudet and I. M. L. Billas (2022). "A novel nuclear receptor subfamily enlightens the origin of heterodimerization." BMC Biol 20(1): 217.
  3. Fontaine, E., C. Papin, G. Martinez, S. Le Gras, R. A. Nahed, P. Héry, T. Buchou, K. Ouararhni, B. Favier, T. Gautier, J. S. M. Sabir, M. Gerard, J. Bednar, C. Arnoult, S. Dimitrov and A. Hamiche (2022). "Dual role of histone variant H3.3B in spermatogenesis: positive regulation of piRNA transcription and implication in X-chromosome inactivation." Nucleic Acids Research 50(13): 7350-7366.
  4. Rovito, D., A.-I. Rerra, V. Ueberschlag-Pitiot, S. Joshi, N. Karasu, V. Dacleu-Siewe, Khalil B. Rayana, K. Ghaibour, M. Parisotto, A. Ferry, Scott A. Jelinsky, G. Laverny, Bruno P. Klaholz, T. Sexton, I. M. L. Billas, D. Duteil and D. Metzger (2021). "Myod1 and GR coordinate myofiber-specific transcriptional enhancers." Nucleic Acids Research 49(8): 4472-4492.
  5. Beinsteiner, B., G. V. Markov, S. Erb, Y. Chebaro, A. G. McEwen, S. Cianférani, V. Laudet, D. Moras and I. M. L. Billas (2021). "A structural signature motif enlightens the origin and diversification of nuclear receptors." PLoS Genet 17(4): e1009492.
  6. Ibrahim, A., C. Papin, K. Mohideen-Abdul, S. Le Gras, I. Stoll, C. Bronner, S. Dimitrov, B. P. Klaholz and A. Hamiche (2021). "MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion." Science 372(6549): eabd5581.
  7. Papin, C., S. Le Gras, A. Ibrahim, H. Salem, M. M. Karimi, I. Stoll, I. Ugrinova, M. Schröder, E. Fontaine-Pelletier, Z. Omran, C. Bronner, S. Dimitrov and A. Hamiche (2021). "CpG Islands Shape the Epigenome Landscape." Journal of Molecular Biology 433(6): 166659.
  8. Boopathi, R., S. Dimitrov, A. Hamiche, C. Petosa and J. Bednar (2020). "Cryo-electron microscopy of the chromatin fiber." Current Opinion in Structural Biology 64: 97-103.
  9. Khalturin, K., I. M. L. Billas, Y. Chebaro, A. M. Reitzel, A. M. Tarrant, V. Laudet and G. V. Markov (2018). "NR3E receptors in cnidarians: A new family of steroid receptor relatives extends the possible mechanisms for ligand binding." The Journal of Steroid Biochemistry and Molecular Biology 184: 11-19.
  10. Markov, G. V., J. Gutierrez-Mazariegos, D. Pitrat, I. M. L. Billas, F. Bonneton, D. Moras, J. Hasserodt, G. Lecointre and V. Laudet (2017). "Origin of an ancient hormone/receptor couple revealed by resurrection of an ancestral estrogen." Science Advances 3(3): e1601778.
  11. Mohideen-Abdul, K., K. Tazibt, M. Bourguet, I. Hazemann, I. Lebars, M. Takacs, S. Cianférani, B. P. Klaholz, D. Moras and I. M. L. Billas (2017). "Importance of the Sequence-Directed DNA Shape for Specific Binding Site Recognition by the Estrogen-Related Receptor." Frontiers in Endocrinology 8(140).

Modalités de candidature

The group of Dr. Ali Hamiche (IGBMC) is looking for an excellent, highly motivated and self-organized postdoctoral candidate to investigate how the glucocorticoid receptor associated complexes regulates gene expression using molecular biology, biochemistry and structural biology approaches. The position is available from 01 February 2023 or as soon as possible thereafter. The position will initially be limited to 2 years but can be extended to 4 years depending on your performance.

 

Your application must be submitted electronically to Dr. Isabelle Billas (billas@igbmc.fr) and should include:

  • Cover letter describing your motivation and qualifications for the position
  • CV incl. education, work/research experience, language skills and other skills relevant for the position.
  • Complete publication list
  • A certified/signed copy of a) PhD certificate and b) Master of Science certificate. If the PhD is not completed, a written statement from the supervisor will do.
  • Separate reprints of 3 particularly relevant papers
  • Contact information of at least two references

Associé à :

Profil

We are specifically looking for someone with significant experience in eukaryotic cell culture techniques, biochemistry, purification of recombinantly expressed proteins and protein structural characterization.

  • PhD in biology, biochemistry, structural biology or in related field.
  • A strong background in protein biochemistry and insect and/or mammalian cell culture techniques.
  • Experience in cryo-electron microscopy sample preparation, data acquisition and analysis would represent a strong advantage.
  • Strong team player and networking skills.
  • You should have an interest in supporting the supervision of master and doctoral students.
  • Publications in high-quality journals and presentations at international conferences
  • Ability to manage a research project and the associated resources

 

As a postdoctoral candidate, you will have the opportunity to work on an interesting and challenging project that will profit from your enthusiasm, creativity and willingness to implement new methodology. 

The duration of the position is 2 years with a possibility of extension, depending on performance.

Remuneration and social benefits will be based on the CNRS agreement for public-sector employees.