Reference : UMR5203-MATMAN-003
Workplace : MONTPELLIER
Date of publication : Monday, April 11, 2022
Type of Contract : FTC Scientist
Contract Period : 24 months
Expected date of employment : 1 September 2022
Proportion of work : Full time
Remuneration : 2500-2700 Euros
Desired level of education : PhD
Experience required : 1 to 4 years
The fellow will develop a project on the functional roles of cardiac G protein gated potassium (Girk4) channels encoding for IKACh and of L-type Cav1.3 calcium channels in cardiac automaticity in physiological conditions and upon sinus node dysfunction. The objective of the project is to establish Girk4 channels as therapeutic targets for managing dysfunction of heart automaticity and bradycardia. The Fellow's project is integrated into the general objectives of Fondation Leducq FANTASY Transatlantic Network of Excellence (https://sites.google.com/view/fantasyleducq/home). The Fellow will be integrated in the FANTASY Network et will benefit of internal scientific exchanges and collaborative program in a scientific environment of excellence.
- In vivo exploration of mouse models carrying mutant Girk4, Cav1.3 and HCN4 alleles.
- Ex vivo study of cardiac automaticity of isolated hearts and intact sinoatrial node tissue by employing optical mapping of membrane voltage and intracellular calcium.
- Patch-clamp recording of native cardiac sinoatrial pacemaker myocytes and cardiomyocytes differentiated from human pluripotent stem cells (hiPS-CM).
- Imaging of intracellular calcium and cAMP dynamics in native pacemaker myocytes and hiPS-CM.
- Selective vector-based targeting of Girk4 and Cav1.3 expression.
- Selective pharmacology of Girk4 and Cav1.3 channels.
- Experience in patch-clamp recordings of cardiac myocytes.
- Experience in confocal microscopy and confocal imaging of intracellular calcium dynamics.
- Experience in basic techniques of molecular biology and biochemistry: PCR, Western blot, RNAseq.
- Experience in immunofluorescence and immunohistochemistry would be suitable.
- Use of analysis and imaging software.
- Ability to write and present in English.
- Previous experience on ECG recording would be suitable.
- Possibility of on-site learning of specific techniques of genomics, proteomics, molecular pharmacology, vector-based gene knock-down, small animal imaging and immunohistochemistry via dedicated teaching courses of Biocampus core facilities.
All necessary instruments and experimental approaches will be rendered available to the Fellow to ensure project feasibility and success. The IGF is a pluridisciplinary centre of excellence, which combines physiology with neuroscience and cancer biology. The Fellow will benefit of a highly stimulating scientific environment within the IGF and the FANTASY Network. The Fellow will work under the responsibility of PI Matteo Mangoni in the team “Physopathology of heart rhythm and ischemia”. (https://www.igf.cnrs.fr/index.php/fr/h-teams-fr/ht-barrere-fr). The team associates internationally leading experts in ion channels and heart automaticity with experts in ischemia-reperfusion. 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 two patch-clamp setups, a Langerdorff isolated heart setup, optical mapping of membrane voltage/intracellular calcium and an Ionoptix system to measure contraction and calcium transients. 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.
Constraints and risks
No particular risks or constraints are to be expected. No exposure to pathogenic agents. Usage of human derived sample is established according to Institutional guidelines.
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