Post Doc - B.Reina San Martin Team
Reference : Post doc B.R-S-M
Offer publication : May 2, 2017
Postdoctoral position in the field of Molecular Immunology.
The Reina lab is seeking a highly motivated and experienced postdoctoral fellow to study the molecular mechanisms driving B cell receptor diversification during immune responses, with a particular focus on immunoglobulin class switch recombination (CSR). CSR modulates antibody effector functions by replacing the isotype expressed (from IgM to IgG, IgA or IgE) through a DNA recombination reaction (occurring at the IgH locus) that requires double stranded DNA break (DSBs) intermediates induced by activation-induced cytidine deaminase (AID). These DSBs activate DNA damage response proteins to promote appropriate repair and long-range recombination. While on-target lesions are crucial for Ig diversification, off-target lesions contribute to malignant cell transformation and AID has been strongly implicated in the initiation of cancer. Despite the significant potential of AID to inflict collateral DNA damage, most B cells expressing AID do not suffer widespread mutation or chromosome instability. Therefore, it appears that specific regulatory mechanisms actively restrict AID's oncogenic potential. The selected postdoctoral fellow will build on the expertise of the lab, in particular in genome editing using the CRISPR/Cas9 system, to investigate the molecular mechanisms that control the function of AID during CSR and that limit its oncogenic potential.
Applicants must be highly motivated and have a PhD or equivalent doctoral degree with at least 3 years of proven research experience in Molecular Biology, Immunology or Biochemistry. Candidates should have a good publication record and should be fluent in English (French is not required). Good communication skills (oral and written) and the ability to work in a team are essential.
The Reina Lab has a strong publication record and has made in the past few years substantial contributions to the understanding of the molecular mechanisms that mediate CSR. Approaches used include molecular and cellular techniques, genome editing (CRISPR/Cas9), gene targeting, mouse genetics, mass spectrometry, in vitro cell differentiation assays, flow cytometry, ChIP-Seq and 4C-Seq analysis. The candidate will benefit from a rich scientific environment at IGBMC, including access to several state-of–the art research facilities.
- Robert, I., et al. Robust immunoglobulin class switch recombination and end-joining in Parp9-deficient mice. Eur J Immunol (2017).
- Tsouroula, K., et al. Temporal and Spatial Uncoupling of DNA Double Strand Break Repair Pathways within Mammalian Heterochromatin. Mol Cell 63, 293-305 (2016).
- Thomas-Claudepierre, A.S., et al. Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination. J Exp Med 213, 303-312 (2016).
- Robert, I., et al. Parp3 negatively regulates immunoglobulin class switch recombination. PLoS Genet 11, e1005240 (2015).
- Thomas-Claudepierre, A.S., et al. The cohesin complex regulates immunoglobulin class switch recombination. J Exp Med 210, 2495-2502 (2013).
- Willmann, K.L., et al. A role for the RNA pol II-associated PAF complex in AID-induced immune diversification. J Exp Med 209, 2099-2111 (2012).
- Jeevan-Raj, B.P., et al. Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination. J Exp Med 208, 1649-1660 (2011).
- Robert, I., Dantzer, F. & Reina-San-Martin, B. Parp1 facilitates alternative NHEJ, whereas Parp2 suppresses IgH/c-myc translocations during immunoglobulin class switch recombination. J Exp Med 206, 1047-1056 (2009).
Applications should be addressed by e-mail to Dr. Bernardo Reina-San-Martin (firstname.lastname@example.org) and include a complete curriculum vitae with a short statement of of past and future research interests and the contact information (phone number and email) of at least two referees.