CHLARABIDOX | Discovering genome-wide thiol-dependent metabolic regulation in photosynthesis with redox chemoproteomics

Summary
Most organisms exhibit a diurnal metabolic cycle, especially phototrophs, whose metabolism is strictly dependent on light. Dark-light transitions are accompanied by dramatic changes in the redox state of photosynthetic components, which drives redox-based post-translational modification of protein cysteines, whose oxidation state can considerably impact protein activity, and thus regulate metabolism. Given the central role of redox metabolism in biology, the operation of thiol-disulphide based switches are well-appreciated as a metabolic acclimation strategy, and the study of cysteine modifications in proteomes is a major interest of contemporary biology. The objective of CHLARABIDOX is to go beyond inventories of redox modified proteins by monitoring the proteome-wide dynamics of disulphide-dithiol status in the context of a diurnal metabolic cycle in phototrophic eukaryotes, specifically, the green alga Chlamydomonas reinhardtii and the land plant Arabidopsis thaliana. An innovative chemoproteomic isoTOP-ABPP approach will be used in an experimental design with deep temporal resolution to capture a good fraction of the proteome with site specificity and quantitative information about reactivity. The discoveries will be made in the context of a body of literature on thioredoxin-dependent redox regulation of central carbon metabolism, which will serve as a priori validation. The outcome of the project is a proteome-wide view of the operation of regulatory redox sensors, anchored to accompanying rich datasets on physiology, metabolic potential, transcriptomics, proteomics and central metabolites, which would inform the operation of light-driven metabolic networks. Both systems are compatible with downstream modelling of diurnal metabolic fluxes and validation by reverse genetics approaches. A long term impact on strategies for manipulating metabolism for biofuels production, or manipulating photosynthesis for better acclimation to climate change is also envisioned.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/887992
Start date: 01-06-2020
End date: 08-12-2023
Total budget - Public funding: 263 732,16 Euro - 263 732,00 Euro
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Original description

Most organisms exhibit a diurnal metabolic cycle, especially phototrophs, whose metabolism is strictly dependent on light. Dark-light transitions are accompanied by dramatic changes in the redox state of photosynthetic components, which drives redox-based post-translational modification of protein cysteines, whose oxidation state can considerably impact protein activity, and thus regulate metabolism. Given the central role of redox metabolism in biology, the operation of thiol-disulphide based switches are well-appreciated as a metabolic acclimation strategy, and the study of cysteine modifications in proteomes is a major interest of contemporary biology. The objective of CHLARABIDOX is to go beyond inventories of redox modified proteins by monitoring the proteome-wide dynamics of disulphide-dithiol status in the context of a diurnal metabolic cycle in phototrophic eukaryotes, specifically, the green alga Chlamydomonas reinhardtii and the land plant Arabidopsis thaliana. An innovative chemoproteomic isoTOP-ABPP approach will be used in an experimental design with deep temporal resolution to capture a good fraction of the proteome with site specificity and quantitative information about reactivity. The discoveries will be made in the context of a body of literature on thioredoxin-dependent redox regulation of central carbon metabolism, which will serve as a priori validation. The outcome of the project is a proteome-wide view of the operation of regulatory redox sensors, anchored to accompanying rich datasets on physiology, metabolic potential, transcriptomics, proteomics and central metabolites, which would inform the operation of light-driven metabolic networks. Both systems are compatible with downstream modelling of diurnal metabolic fluxes and validation by reverse genetics approaches. A long term impact on strategies for manipulating metabolism for biofuels production, or manipulating photosynthesis for better acclimation to climate change is also envisioned.

Status

CLOSED

Call topic

MSCA-IF-2019

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2019
MSCA-IF-2019