Post-doctoral Position on Epigenetics of the Dependence Receptors and their Signaling Pathways
- Inserm UMR 590 Centre Léon Bérard, Lyon, France
An original concept has emerged, based on the notion that a receptor unoccupied by its ligand is not necessarily inactive. In the absence of ligand, signaling leads to an active process that results in cell death through apoptosis. The survival of a cell expressing such a receptor can therefore be seen as dependent on the presence of the ligand, hence the concept of “dependence receptors” (DR). The fact that the different DRs trigger apoptosis in the absence of ligand suggests that they may all act as regulators of tumorigenesis. In addition, expression of DRs is lost or decreased in many tumors, suggesting that they act as tumor suppressors and that their loss represents a selective advantage for tumoral cells.
Abnormal patterns of DNA methylation in cancer cells have been recognized for over 20 years. Specifically, aberrant hypermethylation of CpG islands at the 5’ end of tumor-suppressor genes, leading to transcriptional repression, has been described both in cancer cell lines and tumor tissues. The discovery of methyl-CpG binding proteins (MBD) and their interacting partners provides a direct link between DNA methylation and the establishment of repressive chromatin architecture. Four of them, MBD1, MBD2, MBD3 and MeCP2, are directly involved in the transcriptional repression of methylated templates and, with the exception of MBD3, bind methylated DNA.
Our working hypothesis is that these receptors may be the targets of epigenetic modifications leading to their transcriptional silencing as it was observed for many tumor suppressor genes.
Thus a comprehensive analysis of these events needs high-throughput analyses of epigenetic modifications occurring in cancer cells since epigenetic inactivation may not only affects the DR expression but also the genes involved in downstream signaling pathways.
A postdoctoral position will be initially for 1 year and available immediately. The contract can be renewed.
This program will be developed in close collaboration with P. Mehlen laboratory. The candidates will benefit of several approaches already developed in both teams: Robert Dante team has long experience of epigenetic studies (ChIP-chip, new methods for mapping methylated sites) and the concept of Dependence Receptor has emerged from Patrick Mehlen laboratory (several cell lines and mouse models have been already developed).
Qualifications: A solid background in molecular biology is required.
Application Details: Interested applicants should send a cover letter explaining their interests in the project, a curriculum vitae including previous publications and names of three references per E-mail.
Robert Dante, PhD
Unité INSERM 590
Oncogenese et progression tumorale
Centre Léon Bérard
28 rue Laennec
69373 Lyon Cedex 08
Contact: Robert Dante, PhD
Closing Date: Check with institute