Description du sujet de thèse

The PhD project will investigate the physiological and biophysical mechanisms by whose voltage-gated L-type Cav1.3 calcium channels control the generation and regulation of heart pacemaker activity by the autonomic nervous system and the cardiac electromechanical coupling. The project will employ the most advanced techniques in cardiac cellular electrophysiology, calcium imaging, site directed mutagenesis, genomics, proteomics and structural biology of calcium channels. As the outcome of PhD, the candidate will own unique expertise in the domain of ion channels and the possibility of integration into an outstanding international network of teams to pursue postdoctoral research and build an independent career.

Contexte de travail

All necessary instruments and experimental approaches will be rendered available to the trainee to ensure project feasibility and success. The IGF is a pluridisciplinary centre of excellence combining physiology with neuroscience. The trainee will benefit of a highly stimulating scientific environment at the IGF and within the ERA-Net CARDINNOV as well as in the FANTASY Network. The Fellow will work under the responsibility of Matteo Mangoni in the team “Physopathology of heart rhythm and ischemia” (https://www.igf.cnrs.fr/en/teams/team-barrere-lemaire-mangoni/project-ion-channels-in-the-genesis-and-regulation-of-heart-rate-and-rhythm/). The M. Mangoni team is also labelled by the Fondation pour la Recherche Médicale (FRM) and associates internationally leading experts in voltage gated calcium channels (Cav), hyperpolarisation activated channels (HCN) and G protein activated potassium channels (GIRK). The team harbors a worldwide unique collection of genetically modified mice carrying modified alleles of ion channels involved in pacemaking. For ex vivo experiments, the team will make available four patch-clamp setups, a Langerdorff isolated heart setup, optical mapping of membrane voltage/intracellular calcium. Microscopy suitable for confocal recording of calcium dynamics, FRET and BRET and super-resolution of protein staining is also available in core facilities of the Arnaud de Villeneuve campus. For in vivo experiments, the team has a dedicated room equipped with telemetric recording of ECG, blood pressure, and activity, together with laser assisted echocardiograpy.

Contraintes et risques

The thesis topic requires very good capability of integration in a large pluridisciplinary research team involved in international research programmes. It requires willingness to collaborate with the other PhD trainees and postdoctoral fellows of the team, as well as with other teams of the FANTASY network. Strong motivation in learning cellular electrophysiology and biophysics will be the key to success. The employment does not imply radiological or biologicals risks, nor of “on duty” working hours.