Description du projet
Le rôle des espèces réactives de l’oxygène dans la différenciation cellulaire
Les espèces réactives de l’oxygène (ROS pour «reactive oxygen species») sont des dérivés des molécules de dioxygène: ces sous-produits toxiques du métabolisme sont étroitement associés au stress oxydatif. Les faibles niveaux de ROS produits dans les mitochondries (mROS) servent pourtant de signaux pour des processus biologiques ordinaires. Le projet MitoSignal, financé par le Conseil européen de la recherche, étudiera la façon dont les mROS contrôlent la différenciation cellulaire. Les chercheurs utiliseront les parasites du genre Trypanosoma (les agents responsables de la maladie du sommeil) comme organisme modèle simple contenant une mitochondrie unique et subissant divers changements métaboliques au cours du développement programmé. Les résultats de MitoSignal fourniront des informations importantes sur les interactions entre les mitochondries et le reste de la cellule dans le cadre des décisions relatives au destin cellulaire.
Objectif
Mitochondria perform three essential functions: ATP production, metabolite synthesis and cellular signaling. These signals, communicating the bioenergetic and biosynthetic fitness of the organelle to the nucleus, play a powerful role in determining cellular fate. The incorporation of mitochondrial reactive oxygen species (mROS) in cellular signaling is an interesting evolutionary outcome, as excess levels of these potent oxidizers have been implicated in many pathologies. While most research focuses on these outcomes of oxidative stress, much less is known about how mROS drive a range of physiological responses. Furthermore, the available studies are limited to a few traditional model organisms, featuring complex cellular systems with numerous mitochondria at different energetic states. Here, we propose to utilize the unicellular parasites, Trypanosoma brucei and T. congolense, as simplified but elegant models to define mROS-driven cellular differentiation. As these protists undergo programmed development between several distinct life cycle forms, there are striking changes to the structure and physiology of their single mitochondrion that manifest in elevated ROS levels. Importantly, we demonstrated that these ROS molecules are essential for the developmental progression of the parasite. Employing these well-chosen models and combining next-generation biosensors, advanced bioenergetic methods, redox proteomics and a CRISPR/Cas9 genetic screen, we will answer the following fundamental questions: Does mROS drive Trypanosoma cellular differentiation? What molecular processes are responsible for the elevated mROS levels during differentiation? How is the redox signal propagated to the rest of the cell? The proposed research aspires to unravel the fundamental mechanisms underlying the intricate communication between mitochondria and the rest of the cell, featuring cellular hallmarks of cell fate decisions.
Champ scientifique
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsbiosensors
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiology
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
ERC - Support for frontier research (ERC)Institution d’accueil
370 05 Ceske Budejovice
Tchéquie