A post-doctoral position is currently available for 14 months (renewable) in the team Chanelopathies: cystic fibrosis and other diseases, of Research Center "Institut Necker Enfants Malades", INSERM U1151, Faculté Necker, Paris, France.
Salary: 56.000 € / year
Our research concerns the mechanisms involved in Cystic Fibrosis (CF), a lethal genetic disease due to mutations in CF gene. The most frequent mutation, F508del, leads to CFTR misfolding and preferential degradation at the ER, which constitutes the primary cause of the channel functional expression defect at cell surface. Exosomes (EXs), as part of extracellular vesicle populations, have been shown to contain CFTR. Investigating the contribution of selective autophagocytosis of mutated CFTR proteins may bring further insights into in the molecular and cellular pathogenesis of CF, as well as the role of exosome in clearance of misfolded proteins from ER. The study may be extended to other PMD.
The post-doctoral project lies at the interface of biochemistry, molecular cell biology and proteomics, aiming to investigate involvement of EXs in the trafficking and function of CFTR variants. EXs biogenesis and composition, as well as CFTR metabolism will be established in non-polarized cells and epithelia in the presence and absence of CFTR expression. The role of selective autophagocytosis will be probed in parallel by genetic means (siRNA, Crispr). The project will require experience in protein biochemistry, molecular biology, various microscopic and immunochemical techniques. Collaboration with mass spectrometry team is in place.
Candidates for this project should have a solid background in cell culture, cellular, molecular biology (transfection, real time PCR, plasmid construction), and biochemistry (Western Blot, co-immunoprecipitation, immunohistochemistry, microscopy, immunoisolation of organelles, protein biochemistry). Experience in electrophysiology would be an advantage.
Interested candidates should e-mail a letter of application, including a CV and the names and addresses of at least two referees to:
An open call for ERC-funded post-doctoral fellowship positions in the lab of Timothy WAI at INEM (Institut Necker Enfants Malades) located in Paris, France (Inserm U1151, CNRS 8253, Paris Descartes University) for the study of metabolic regulation of mitochondrial dynamics.
Mitochondria are dynamic organelles that can undergo dramatic changes in morphology in response to metabolic inputs by adapting the balance between mitochondrial fusion and fission. Mitochondrial fragmentation occurs in response to nutrient excess and cellular dysfunction and has been observed in cardiovascular and neuromuscular disorders, cancer and obesity.
We recently showed that mitochondrial fragmentation drives heart failure, which can be rescued by dietary and metabolic interventions (Wai et al. Science 2015). Our goal is now to understand how metabolic cues from outside the cell are relayed to mitochondria to affect their form and function, with a particular focus on the molecular events at the mitochondrial inner membrane (Wai et al. EMBO reports 2016).
The Institut Necker Enfants Malades (INEM) is an interdisciplinary Research Centre of Molecular Medicine with two excellent departments in the fields of “immunology, infectiology, and heamatology” and “cell biology”. The recently established laboratory “Immunity in Health and Disease” is looking for highly motivated post-doctoral scientists interested in studying the regulatory functions of B cells in autoimmune and infectious diseases. The project is funded by a European Research Council (ERC) grant awarded to characterize cytokine-producing regulatory plasma cells and pro-inflammatory B cells in autoimmune and infectious diseases. The project will combine novel state-of-the art in vivo genetic models, as well as cellular and molecular approaches to characterize novel disease-relevant B cell subsets. The candidates should have a strong track record in the field of immunology, cellular immunology, and possibly molecular biology. The laboratory “Immunity in Health and Disease” is at the interface between fundamental and clinical research, and the long-term goal of the project is to derive tools useful in the clinic.