Mitochondrial signaling drives parasite differentiation
This project aims to investigate how mitochondrial reactive oxygen species drive cellular differentiation in Trypanosoma parasites using advanced biosensors and genetic techniques.
Projectdetails
Introduction
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.
Mitochondrial Reactive Oxygen Species (mROS)
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.
Research Limitations
Furthermore, the available studies are limited to a few traditional model organisms, featuring complex cellular systems with numerous mitochondria at different energetic states.
Proposed Models
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.
Importance of ROS
Importantly, we demonstrated that these ROS molecules are essential for the developmental progression of the parasite.
Research Methodology
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?
Research Aspirations
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.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 1.991.125 |
Totale projectbegroting | € 1.991.125 |
Tijdlijn
Startdatum | 1-1-2023 |
Einddatum | 31-12-2027 |
Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- BIOLOGICKE CENTRUM AKADEMIE VID CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCEpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
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The molecular nexus coupling Cell Metabolism to Cell cycle and Genome SurveillanceThis project aims to explore how reactive oxygen species (ROS) influence DNA replication and cell cycle dynamics during early development and cancer, using advanced cellular models and innovative analytical tools. | ERC Starting... | € 1.499.329 | 2023 | Details |
A sense of direction: cooperative behaviour and chemotaxis in the life cycle of Trypanosoma bruceiThis project aims to uncover the mechanisms of cAMP-mediated pH sensing and chemotaxis in Trypanosoma brucei to understand its organ colonization and migration strategies in hosts. | ERC Advanced... | € 2.499.228 | 2024 | Details |
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Revival of the Powerhouse: How mitochondrial remodelling controls the energy metabolism of the malaria parasite to enable survival in different hosts
This project aims to elucidate the structure and function of Plasmodium falciparum mitochondria to inform antimalarial drug discovery by using advanced structural and functional techniques.
The molecular nexus coupling Cell Metabolism to Cell cycle and Genome Surveillance
This project aims to explore how reactive oxygen species (ROS) influence DNA replication and cell cycle dynamics during early development and cancer, using advanced cellular models and innovative analytical tools.
A sense of direction: cooperative behaviour and chemotaxis in the life cycle of Trypanosoma brucei
This project aims to uncover the mechanisms of cAMP-mediated pH sensing and chemotaxis in Trypanosoma brucei to understand its organ colonization and migration strategies in hosts.
Decoding the path to cellular variation within pathogen populations
The project aims to uncover the molecular mechanisms behind cell-to-cell heterogeneity in Trypanosoma brucei to inform strategies for combating pathogen adaptation and drug resistance.
Mitochondrial Precursor Proteins in the Cytosol as Major Determinants of Cellular Health
MitoCyto aims to uncover the biology of cytosolic mitochondrial precursor proteins using innovative interdisciplinary techniques to enhance understanding of cellular proteostasis and its implications for aging and neurodegeneration.