Project description
Reactive oxygen species in cell differentiation
Reactive oxygen species (ROS) are derivatives of molecular oxygen that are toxic byproducts of metabolism closely associated with oxidative stress. However, low ROS levels produced in mitochondria (mROS) serve as signals for normal biological processes. The MitoSignal project, funded by the European Research Council, will investigate how mROS drive cell differentiation. Researchers will use Trypanosoma parasites – the causative agents of sleeping sickness – as a simple model organism containing a single mitochondrion that undergoes various metabolic changes during programmed development. MitoSignal results will provide important insights into the interplay between mitochondria and the rest of the cell in cell fate decisions.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors biosensors
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-COG
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370 05 Ceske Budejovice
Czechia
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