10/09/2021

PostDoctoral position for 3-years starting from December 2021

This job offer has expired


  • ORGANISATION/COMPANY
    Inserm U955
  • RESEARCH FIELD
    Biological sciencesBiology
    Medical sciencesMedicine
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
    Recognised Researcher (R2)
  • APPLICATION DEADLINE
    10/10/2021 23:00 - Europe/Brussels
  • LOCATION
    France › Creteil
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    35
  • OFFER STARTING DATE
    01/12/2021
  • REFERENCE NUMBER
    196

OFFER DESCRIPTION

Deciphering molecular signatures of pre-malignant lesions in Neurofibromatosis type 1 (NF1)

Institut Mondor of Biomedical Research (IMRB); INSERM U955, Creteil, France

We seek to hire a highly motivated postdoctoral fellow to work on exploring genetic, epigenetic and transcriptomic alterations driving malignant transformation in NF1. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with no effective therapy. In half of cases, they occur in NF1 patients, a genetic disorder caused by mutations in the NF1 tumor suppressor gene. NF1 patients develop benign nerve sheath tumors, called plexiform neurofibromas (pNFs), known to arise from the NF1-/- Schwann cells (SC) with hyperactive RAS pathway. About 10% of pNFs transform into MPNSTs. This progression is preceded by a pre-neoplastic state, termed as “dysplastic” NF (dNF) and characterized by increased proliferative activity of NF1-/- SCs and heavy but transient infiltration by T lymphocytes. The malignant transformation is driven by acquisition by mutant SCs of additional mutations in tumor suppressor genes. Our team has developed a Nf1-KO mouse model that successfully recapitulates the development of pNFs and their transformation into MPNSTs through a dysplastic phase. This project aims to apply multi-omics approach on dNFs issued from this mouse model and from NF1 patients to address key questions concerning molecular events underlying malignant transformation of NFs. First, by performing biobanking followed by genetic, epigenetic and transcriptomic analyses of tumor cells we expect identifying molecular alterations and candidate genes involved in this process. Next, by grafting individually barcoded tumor cells into nude recipients, and analyzing developing tumors at successive transformation steps, we will rank these molecular modifications, and set up a patient-derived xenograft model for drug screening essays. Last, by grafting tumor cells carrying permanent inactivation of candidate genes, we expect to functionally validate their role in progression of dNFs into MPNSTs.

The Postdoc candidate should have expertise in both cellular and molecular biology applied to cancer. A background in single cell molecular analyses (epigenetics and transcriptomics), both experimental procedure and bioinformatic analysis would be appreciated but not required. The post-doc candidate will integrate our young and dynamic team including Postdocs, engineers and PhD students located at IMRB. IMRB is one of the major pluridisciplinary biomedical research centres in the eastern part of the Paris region. The research teams develop high-standing basic and translational research in a wide variety of fields in direct connection with healthcare services and a large number of patient cohorts. It comprises almost 600 people belonging to 14 research teams, and 4 technological platforms.

Selected publications of the host team relative to the project:

Radomska, K. J. et al. Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells. Cancer Discov 9, 130-147 (2019).

Gresset, A. et al. Boundary Caps Give Rise to Neurogenic Stem Cells and Terminal Glia in the Skin. Stem Cell Reports 5, 278-290 (2015).

Website: https://www.imrb.inserm.fr

More Information

Additional comments

Interested candidates should send their CV, a motivation letter including research interests and names of 2 referees

Offer Requirements

  • REQUIRED LANGUAGES
    ENGLISH: Good

Skills/Qualifications

The Postdoc candidate should have expertise in both cellular and molecular biology applied to cancer

Specific Requirements

A background in single cell molecular analyses (epigenetics and transcriptomics), both experimental procedure and bioinformatic analysis would be appreciated but not required. The post-doc candidate will integrate our young and dynamic team including Postdocs, engineers and PhD students located at IMRB. IMRB is one of the major pluridisciplinary biomedical research centres in the eastern part of the Paris region. The research teams develop high-standing basic and translational research in a wide variety of fields in direct connection with healthcare services and a large number of patient cohorts. It comprises almost 600 people belonging to 14 research teams, and 4 technological platforms

Work location(s)
1 position(s) available at
Institut Mondor for Biomdecial Research
France
Ile de France
Creteil
94010
8 rue de General Sarrail

EURAXESS offer ID: 682688

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