Thesis defense Hugo Millet

Equipe

Team II - Ion channels and cardiopathies

Directeur de thèse

Michel De Waard
 

Co-Encadrant

Jérôme Montnach

Rapportrices

Stéphanie Barrere-Lemaire, PhD, DR CNRS, Institut de Génomique Fonctionelle, Montpellier
Evelyne Benoit, PhD,  CRCN CNRS, CEA, Université Paris-Saclay, Paris

Examinateurs

Isabelle Baro-Puigdemasa, PhD, DR Inserm, l'institut du thorax, Nantes
Pietro Mesirca, PhD,  CRCN Inserm, Institut de Génomique Fonctionelle, Montpellier
Alexandre Mourot, PhD, DR Inserm, Laboratoire Plasticité du Cerveau, ESPCI, Paris 

Abstract

Cardiac arrhythmias are a major public health issue, often linked to ion channel dysfunction. My thesis project focuses on the voltage-gated sodium channels expressed in the heart, in particular the isoforms sensitive to tetrodotoxin (TTX-S). Although their expression is in the minority compared with NaV1.5, their role in the emergence of arrhythmias remains poorly understood. My aim is to identify the isoforms involved in these disorders and to gain a better understanding of their functions at different scales in the living world. To do this, I am using peptides derived from animal venoms, which have a remarkable affinity and selectivity for certain isoforms, in order to target them precisely. Part of my project also involves developing photopharmacological approaches to spatio-temporally control the activity of these peptides. These innovative tools will enable me to explore the functional impact of these channels in cellular, tissue and animal models. By combining pharmacological and photopharmacological approaches, this research aims to shed light on the molecular mechanisms of arrhythmias and lay the foundations for the development of new targeted therapeutic strategies that are more effective and have fewer side effects than current treatments.