We are looking for a highly-motivated Post-doctoral Research Scientist with knowledge in cell biology to join the lab “membrane traffic and pathogenesis” headed by Chiara Zurzolo.

Rôle des « Tunneling nanotubes » (TNTs) dans l’hétérogénéité tumorale, la formation des réseaux et la résistance aux thérapies Understanding the role of Tunneling nanotubes (TNTs) in tumor networking, heterogeneity and resistance to therapy

Project Intra-tumoral heterogeneity plays major roles in tumor proliferation/migration and invasion, as well as in tumor evasion and chemotherapy resistance. How cells communicate in the complex and dense heterogeneous tumor matrix in invasive cancers has become a major research area. The recent discovery of cellular connections called tunneling nanotubes (TNTs) or tumor microtubes (connecting cancer cells and between cancer and stromal and/or endothelial cells) in several aggressive forms of cancer points towards a novel mechanism for tumor molecular networking that appears to be key for cancer development and might be instrumental for its treatment (Connor et al, Nature Com, 2015; Osswald et al, Nature, 2015). Both glioblastoma (GMB) and neuroblastoma (NB) are well characterized for tumor heterogeneity and ability to trans-differentiate following therapeutic treatment, which results in therapy resistance and development of a more aggressive phenotype. Furthermore, TNT-like structures form between GMB and NB derived cells, exchange materials through them and correlate with more aggressive phenotype. Tunneling nanotubes (TNTs) are F-actin containing channels formed between remote cells, they emerged as a new mechanism for long-range intercellular communication in many cell types and contexts (Abounit and Zurzolo, J. Cell Sci, 2012; Baker, Nature, 2017). Unlike other filamentous bridges (e.g., filopodia, cytonemes), TNTs directly connect the cytoplasm of distant cells, and selectively transfer a wide variety of cellular materials, such as cytoplasmic molecules, miRNA, vesicles and organelles. The lab has pioneered studies in the TNT field demonstrating that they are involved in prions and amyloid protein dissemination (Gousset et al, Nat Cell Biol, 2009, Abounit et al, EMBO J, 2016, Victoria and Zurzolo, J Cell Biol, 2017) and they are distinct from filopodia (Delage et al, Sci Rep, 2016* ; Sartori-Rupp, Cordero Cervantes et al, bioRxiv, 2018*). In this project we will use a multidisciplinary approach combining cell biology, quantitative imaging, transcriptomic, bioinformatics and tumor physiology to: i) evaluate the participation of TNT-based communication into the networking among phenotypically different tumors (GBM and NB), depending on the genetic/epigenetic background; ii) define the role and appearance of TNTs in treatment responses; iii) characterize TNTs, both structurally and functionally within specific tumors in order to identify possible therapeutic targets. While providing novel insights on tumor heterogeneity establishment and consequences, this project will allow understanding the role and effects of TNT mediated intercellular communication in cancer. The translational impact of this proposal is based on the hypothesis that TNT disruption could drain cancer cells by not providing the required network, suggesting that TNTs could be novel promising targets. * publications from the host lab

Laboratory Chiara Zurzolo laboratory is located in the Institut Pasteur, Paris, and benefits from a highly dynamic, international scientific environment at the forefront of science. The lab has pioneered studies of TNTs in the context of prions and other neurodegenerative diseases over the last decade (Gousset and Zurzolo, Prion, 2009; Victoria and Zurzolo, J Cell Biol, 2017). The team of Zurzolo is a world leader in protein trafficking, and membrane biology and has set all experimental conditions for TNT analysis in different tissue culture models (2D, 3D and organoids). They are cell biologist experts in different tissue cultures, advanced confocal fluorescence microscopy, two photon and digital confocal microscopy, Electron Microscopy, FACS, CRISPR-Cas, and real-time PCR. The laboratory is fully equipped for biochemistry, cellular and molecular biology.

Qualifications of the applicant Candidates should hold a PhD in biological or biochemical sciences; first or second post-doc are considered and acquired experience in cell biology and microscopy techniques is welcome but not essential. CV and publication record competitive for national/international post-doctoral fellowships are desirable. Most importantly, strong motivation to pursue a scientific career, curiosity driven, organizational and team working abilities, as well as capacity to take projects from conception to completion are required. Verbal and written communication skills in English are essential.

Application details The post-doctoral fellow will use a multidisciplinary approach combining cell biology, quantitative imaging, transcriptomic, in collaboration with bioinformatics team in Cochin institute. The postdoctoral fellow will have access to the leading-edge core facilities available within the Institut Pasteur. The project is funded by Institut du Cancer for up to 3 years. Applications including a CV and a cover letter summarizing current and future research interests, as well as the contact details of 2 referees, should be sent by e-mail to chiara.zurzolo@pasteur.fr / christel.brou@pasteur.fr

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