Lung cancers are caused by tobacco smoking but there is a genetic susceptibility to their development, notably through a missense mutation in the a5 nicotinic receptor gene, carried by 30% of the European population. While it was discovered 15 years ago, the effect of this mutation is still not understood at the molecular and protein level. We suspect the mutation affects distribution of the a5 receptors in neurons or respiratory epithelium or that it interferes with a5 interaction with cytoplasmic partners. We propose to reveal the mechanism by which the mutation induces such a strong susceptibility to both nicotine addiction and lung cancer. We will develop specific and accurate camelid antibodies fragments (nanobodies) to examine the distribution of WT and mutant receptor in native conditions. We will use those nanobodies to identify stable partners of a5 receptors and in parallel we will develop proximity labeling approaches to capture transient partners. Comparison of WT and mutant cells will pinpoint those affected by the presence of the mutation.
This proposal will allow us to better understand the role of a5 in lung cancer development in smokers and in never-smokers. Furthermore, results will open paths to the development of new therapeutics targeting so far unexplored signaling cascades to prevent a highly prevalent cancer that kills around 1.8 million people each year. This collaborative project is funded by the Institut National du Cancer (INCa).
We are looking for a highly motivated junior postdoc to conduct most part of the project and starting in April/May 2026. The candidate will have expertise in molecular and cellular biology and will notably perform labelling and imaging by STED of primary culture, modification of the cells by CRISPR-Cas9 to introduce mutations, and interactome techniques.
Expected profile:
- The applicant should have a PhD in cellular biology or neurobiology.
- Experience in molecular biology, primary culture maintenance and/or CRISPR technology and/or proximity labeling is expected.
- Experience in confocal imaging and/or super-resolution microscopy would be a plus.
The proposed research will be supervised by Dr Marie Prevost (https://research.pasteur.fr/en/member/marie-prevost/) and hosted by the Signalization and Receptors Dynamics Unit of the Institut Pasteur (Paris, France). The project is part of a collaboration with Gaël Moneron (super-resolution microscopy) and Gabriel Aymé (nanobodies production). The Institut Pasteur offers excellent scientific environment with high-quality facilities and equipment and strong young researchers’ communities. The project is expected to start in April/May 2026.
Applications including a short description of how relevant your profile is, a CV, and references contacts should be sent to marie.prevost@pasteur.fr before 31st of December.