Projet 3

Thesis project

A Chloride permeability sensitive to volume variation has been described in most of the eukaryote cells. This ubiquitous Cl- conductance plays a major role in regulatory volume decrease (RVD) 1 and apoptotic volume decrease (AVD) processes 2. Since more than 30 years the molecular identity of this conductance has remained elusive. In 2014, 2 independent studies 3, 4 have demonstrated the involvement of a new family of membrane proteins (LRRC8A/swell) in the generation of a volume sensitive Cl- conductance opening new perspectives of research in this field.

 The aim of this original project is to establish the roles and the functions of this new family of channels in 1/ cell division, 2/ in apoptotic progression and 3/ in different cellular processes (epithelial mesenchymal transition and the behavior of immune cells). Extensively, animal model will be developed to study the importance of the LRCC8 family in kidney physiology and/or differentiation of immune cells. This project will focus on this new family of proteins to identified new processes and innovative targets to prevent kidney fibrosis and renal failure 5

We are looking for strongly motivated candidates with interest in cell volume regulation and ions transport. The candidate will be formed to various techniques including electrophysiology (patch-clamp), fluorescence video-microscopy and/or flow cytometry analysis. Basic techniques of biochemistry and cell biology will be also developed during the PhD.

 

1. Barriere, H. et al. Am J Physiol Renal Physiol 284, F796-811 (2003).

2. L'Hoste, S. et al. Free Radic Biol Med 46, 1017-31 (2009).

3. Voss, F. K. et al. Science 344, 634-8 (2014).

4. Qiu, Z. et al. Cell 157, 447-58 (2014).

5. Liu, Y. J Am Soc Nephrol 15, 1-12 (2004).

 

CNRS-UMR 7370 -Laboratoire de Physiomedecine moléculaire, Université de Nice-Sophia antipolis Faculté de Médecine, 28 Av Valombrose, Tour Pasteur

06108 Nice, France.   e-mail to Christophe Duranton or Isabelle Rubera