PhD position in Nice, France

REGULATION OF ION CHANNELS IN CARCINOGENESIS

PhD position (CNRS/PACA funding) available from September 2010 in the Institute of

Developmental Biology and Cancer (UNSA CNRS UMR 6543), in the group of Dr Franck

Borgese at the University of Nice Sophia Antipolis / CNRS, Nice, France.

Thesis supervisor: Dr Olivier Soriani

Our project will focus on the regulation of ion channels involved in cancer cell behaviour

(apoptosis resistance, extra cellular matrix adhesion and degradation, motility, proliferation).

Recently, we have demonstrated that a unique tumour biomarker, the sigma-1 receptor

(Sig1R), was functionally associated to Cl- and K+ channels in lung cancer and leukaemia

cells. We have shown that the over-expression of Sig1R in cancer cells enhances cell

apoptotic resistance through a decrease of volume-regulated Cl- channels activation kinetics

(Renaudo et al., 2007; Le Guennec et al., 2008). Moreover, exogenous sigma ligands inhibit

cell cycle through a K+ channel / p27kip1-dependent pathway (Renaudo et al. 2004).

The project will deal on the molecular mechanisms associating the Sig1R to ion channels

aberrantly expressed in leukaemia and breast cancer cells, in relation to their

aggressiveness state. Finally, in vivo significance of the described mechanisms will be

explored in a mouse metastatic model.

Main technical approaches: Molecular cell biology, genetics, microscopy imagery and

electrophysiology (patch-clamp).

We are seeking highly talented and self-motivated candidates. A background in the field of

electrophysiology and cell physiology will be appreciated. The position will be available on

September 2010.

Candidates are invited to obtain application forms from soriani@unice.fr or borgese@unice.fr

Application deadline: Friday 30th April.

Provisional date for auditions of short listed candidates: Monday 17th May

Références:

· Martial,S., Giorgelli,J.L., Renaudo,A., Derijard,B., and Soriani,O. (2008). SP600125 inhibits Kv

channels through a JNK-independent pathway in cancer cells. Biochem. Biophys. Res.

Commun. 366, 944-950

· Renaudo,A., L'Hoste,S., Guizouarn,H., Borgese,F., and Soriani,O. (2007). Cancer cell cycle

modulated by a functional coupling between sigma receptors and Cl- channels. J. Biol. Chem.

282, 2259-2267.

· Le Guennec,J.Y., Ouadid-Ahidouch,H., Soriani,O., Besson,P., Ahidouch,A., and Vandier,C.

(2007). Voltage-gated ion channels, new targets in anti-cancer research. Recent Patents

Anticancer Drug Discov. 2, 189-202.

· Renaudo,A., Watry,V., Chassot,A.A., Ponzio,G., Ehrenfeld,J., and Soriani,O. (2004). Inhibition

of tumor cell proliferation by sigma ligands is associated with K+ Channel inhibition and

p27kip1 accumulation. J. Pharmacol. Exp. Ther. 311, 1105-1114.