The physiologic response of an organ basically relies on a complex interplay between the different cell types structuring its tissue. At the cellular level, the response arises from the plasma membrane through different receptors, channels, pumps… that integrate and process the extracellular stimuli (chemical, mechanical). Alteration of the plasma membrane response is a hallmark of a number of pathophysiological situations. Now, how the plasma membrane and the overall cell architecture behave in such pathologies and what is the impact on the surface organization and functions of the proteins inserted in the plasma membrane still remain poorly understood. This is however of major interest in pharmacological medicine since most marketed drugs target these plasma membrane proteins.
In this context, the research program of our team focuses on understanding the relationship between the architecture of cardiac tissue (more precisely of the cardiac contractile cells) on the function and pharmacology of the heart and but also on the brain.
Our specific interests are subdivided in three main projects all around the notion of heart architecture:
Ø Identification of the molecular determinants of adult cardiomyocyte morphology & cardiac tissue organization
Ø Characterization of the Heart / Brain axis
Ø Exploration of cardiac cell surface GPCR architecture as a molecular basis underlying biased agonism efficacy of ligands (pharmacology of GPCR).
Our team is highly interdisciplinary integrating people from basic and medical research. As a consequence, our approach also relies on a high interdisciplinarity starting from the identification of the molecular/cellular mechanisms to the integration in animal models but also in humans thanks to our collaboration with the Toulouse University Hospital.
Technical specific skills:
- BRET-based study of protein-protein interactions as well as of protein conformational changes in real time and in living cells.
- Signaling II-messengers quantification
- Nanoscale imaging: Atomic Force microscopy and electron microscopy (TEM, SEM).
- Tissue histomorphology/immunohistology.
- Transgenic mouse models.
- Neonatal/Adult cardiomyocytes primary culture.
- Cardiac in vivo phenotyping: echocardiography, ECG, Heart Rate Variability, Muscle and renal sympathetic nerve activity microneurography