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