Descripción del proyecto
Especies reactivas de oxígeno en la diferenciación celular
Las especies reactivas del oxígeno (ERO) son derivados del oxígeno molecular que constituyen subproductos tóxicos del metabolismo que están estrechamente relacionados con el estrés oxidativo. Sin embargo, los bajos niveles de ERO producidos en las mitocondrias (mERO) actúan como señales para los procesos biológicos normales. El equipo del proyecto MitoSignal, financiado con fondos del Consejo Europeo de Investigación, estudiará el modo en que las mERO impulsan la diferenciación celular. Los investigadores utilizarán parásitos «Trypanosoma», los agentes causantes de la enfermedad del sueño, como organismo modelo simple con una sola mitocondria sometida a diversos cambios del metabolismo durante el desarrollo programado. Los resultados de MitoSignal aportarán información importante sobre la interacción entre las mitocondrias y el resto de la célula en las decisiones sobre el destino celular.
Objetivo
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.
Ámbito científico
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsbiosensors
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiology
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
ERC - Support for frontier research (ERC)Institución de acogida
370 05 Ceske Budejovice
Chequia