Post-doc Chemistry, In Nice, France

A two-year postdoctoral position is available in the Ion Channel Genetics team at IPMC -

TIANP (UMR CNRS 6097) located at the Science faculty in Parc Varlose in Nice, south of

France ( http://www.unice.fr/tianp).

Subject: TASK K+ channel contribution in breathing adaptation to O2, CO2 and

pH changes

Context of the study

The chemosensitivity is an essential property of the respiratory system to permanently adapt

its activity to the needs of the body. Specialized sensors at the periphery (mainly carotid

bodies) and at the central level (specialized nuclei in the brainstem) are involved in

monitoring arterial blood CO2 and O2 pressures as well as pH. Defects of central

chemoreception are implicated in respiratory pathologies such as sleep apnea syndromes,

periodic breathing in high altitude and drug- or anesthesia-induced respiratory depression.

The congenital central hypoventilation syndrome is a severe hereditary form of central

breathing chemosensitivity in human. The brainstem topology of respiratory nuclei is

relatively well known. Yet, we don't precisely know what are the neurons directly involved in

chemosensitivity and even less the exact molecular identities of the chemoreceptors.

Background K+ channels (K2P) of the TASK family display functional characteristics

including pH and reactive oxygen species (ROS) sensitivities that make them good CO2 and

O2 sensors candidates.

In a recently published work, we have identified TASK2 as the molecular O2 sensor in

retrotrapezoid nucleus (RTN) and proposed that its activation by hypoxia generated ROS is

the mechanism by which central hypoxia-induced ventilatory depression takes place

(Gestreau et al 2010).

Objectives

The project is aimed at the characterization of the molecular mechanisms regulating the CO2

and O2 sensing in the brainstem and involved in the adaptation of breathing to the blood gases

relying on the unique model of TASK mutant mice.

We have produced mice invalidated for the three TASK channel genes task1 (kcnk3), task2

(kcnk5) and task3 (kcnk9) as well as double knockout task1-3 and task2-3. The postdoctoral

fellow will develop patch-clamp studies on brainstem slices from these mouse models.

Therefore, a good experience in electrophysiology, and possibly in electrophysiology on

slices would be greatly appreciated.

Post starting January 2011

Duration 24 months

Contact Jacques Barhanin (jacques.barhanin@ unice.fr).

TIANP UMR6097

Faculté des Sciences

Bâtiment Sciences Naturelles

Parc Valrose

06105 Nice, France

Gestreau, C., D. Heitzmann, J. Thomas, V. Dubreuil, S. Bandulik, M. Reichold, S. Bendahhou, P. Pierson, C. Sterner, J.

Peyronnet-Roux, C. Benfriha, I. Tegtmeier, H. Ehnes, M. Georgieff, F. Lesage, J. F. Brunet, C. Goridis, R. Warth and J.

Barhanin (2010). "Task2 potassium channels set central respiratory CO2 and O2 sensitivity." Proc Natl Acad Sci U S A

107(5): 2325-30.