Section: Partnerships and Cooperations

National Initiatives

ANR EXACARD

We started a collaboration with the STORM team at Inria Bordeaux Sud-Ouest to work on further scaling of the Propag code, to push the limit from about ${10}^4$ to ${10}^6$ parallel processors. A proposal for this project was funded this year by ANR. It allows a postdoc to be employed for 2 years.

ANR MITOCARD

The MITOCARD project (Electrophysiology of Cardiac Mitochondria), coordinated by S. Arbault (Université de Bordeaux, ISM), was granted by the ANR in July 2017. The objective of MITOCARD is to improve understanding of cardiac physiology by integrating the mitochondrial properties of cell signaling in the comprehensive view of cardiac energetics and rhythm pathologies. It was recently demonstrated that in the heart, in striking contrast with skeletal muscle, a parallel activation by calcium of mitochondria and myofibrils occurs during contraction, which indicates that mitochondria actively participate in Ca2+ signaling in the cardiomyocyte. We hypothesize that the mitochondrial permeability transition pore (mPTP), by rhythmically depolarizing inner mitochondrial membrane, plays a crucial role in mitochondrial Ca2+ regulation and, as a result, of cardiomyocyte Ca2+ homeostasis. Moreover, mitochondrial reactive oxygen species (ROS) may play a key role in the regulation of the mPTP by sensing mitochondrial energetics balance. Consequently, a deeper understanding of mitochondrial electrophysiology is mandatory to decipher their exact role in the heart's excitation-contraction coupling processes. However, this is currently prevented by the absence of adequate methodological tools (lack of sensitivity or selectivity, time resolution, averaged responses of numerous biological entities). The MITOCARD project will solve that issue by developing analytical tools and biophysical approaches to monitor kinetically and quantitatively the Ca2+ handling by isolated mitochondria in the cardiomyocyte.

MITOCARD is a multi-disciplinary project involving 4 partners of different scientific fields: the CARMEN team as well as

• ISM, the largest chemistry laboratory of the Université de Bordeaux, where the necessary measurement methods will be developed;

• Liryc, where mitochondria are studied at all levels of integration from the isolated mitochondrion to the intact heart; and

• LAAS, the MiCrosystèmes d'Analyse (MICA) group at the Laboratory of Analysis and Architecture of Systems, which develops the biological microsensors for this project.

The project will

• develop chips integrating 4 different electrochemical microsensors to monitor in real-time key mitochondrial signaling parameters: Ca2+, membrane potential, quinone reduction status, O2 consumption, and ROS production;

• develop microwell arrays integrating ring nanoelectrodes to trap single mitochondria within micrometric chambers and measure locally by combined fluorescence microscopy and electrochemical techniques intra- (by fluorescence) and extra-mitochondrial (electrochemistry) metabolites; and

• develop a mathematical model of mitochondrial Ca2+ and ROS handling built on existing knowledge, new hypotheses, and the measured data.

The model may serve both to assess biological assumptions on the role of mitochondria in Ca2+ signaling and to integrate pathological data and provide clues for their global understanding.

GENCI

GENCI (grand équipement national de calcul intensif) is the agency that grants access to all national high-performance resources for scientific purposes in France. GENCI projects have to be renewed yearly. Our project renewal Interaction between tissue structure and ion-channel function in cardiac arrhythmia, submitted in September 2018, has been granted 8 million core-hours on the three major systems Irene, Occigen, and Turing. This compute time is primarily destined for our research into the interaction between ionic and structural heart disease in atrial fibrillation, Brugada syndrome, and early repolarisation syndrome [7] [65], and for new HPC developments [27].