ROS networks: designs, aging, Parkinson's disease and precision therapies.
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BiBTeXHow the network around ROS protects against oxidative stress and Parkinson's disease (PD), and how processes at the minutes timescale cause disease and aging after decades, remains enigmatic. Challenging whether the ROS network is as complex as it seems, we built a fairly comprehensive version thereof which we disentangled into a hierarchy of only five simpler subnetworks each delivering one type of robustness. The comprehensive dynamic model described in vitro data sets from two independent laboratories. Notwithstanding its five-fold robustness, it exhibited a relatively sudden breakdown, after some 80 years of virtually steady performance: it predicted aging. PD-related conditions such as lack of DJ-1 protein or increased alpha-synuclein accelerated the collapse, while antioxidants or caffeine retarded it. Introducing a new concept (aging-time-control coefficient), we found that as many as 25 out of 57 molecular processes controlled aging. We identified new targets for "life-extending interventions": mitochondrial synthesis, KEAP1 degradation, and p62 metabolism.
SEEK ID: https://fairdomhub.org/publications/586
PubMed ID: 33106503
Projects: ROS detailed model for MSB manucript, SNAPPER: Synergistic Neurotoxicology APP for Environmental Regulation, Service to LCSB (Luxembourg) with respect to ROS management in Parkinso...
Publication type: Journal
Journal: NPJ Syst Biol Appl
Citation: NPJ Syst Biol Appl. 2020 Oct 26;6(1):34. doi: 10.1038/s41540-020-00150-w.
Date Published: 26th Oct 2020
Registered Mode: by PubMed ID
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Created: 23rd Jan 2021 at 18:04
Last updated: 8th Dec 2022 at 17:26
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Institutions: University of Surrey
https://orcid.org/0000-0001-5640-7422
Reader (Professor) of Systems Biology; Executive Director for the International Society of Systems Biology (ISSB); Editor-in-Chief of Current Opinion in Systems Biology (Elsevier).
Projects: SNAPPER: Synergistic Neurotoxicology APP for Environmental Regulation
Institutions: University of Milano-Bicocca
Projects: SNAPPER: Synergistic Neurotoxicology APP for Environmental Regulation, VHP project
Institutions: University Maastricht
Projects: SulfoSys, FAIRDOM user meeting, Service to Milano-Bicocca with respect to their ATP-ROS model (Active NOW), Make Me My Model, Service to University of Lisbon (Portugal) with respect to their CFTR maturation model (Active NOW), Service to LCSB (Luxembourg) with respect to ROS management in Parkinson’s disease and cancer model (Active NOW), Service to URV Tarragona, Spain with respect to their Safety Assessment of Endocrine Disrupting Chemicals model (Active NOW), Service to Universidade Católica Portugues with respect to their Molecular Insight into Autism Spectrum Disorder (ASD) model (Active NOW), Service to Slovenia with respect to their Protease signaling network in neurodegeneration model (Active NOW), Service to University of Duisburg- Essen (Germany): with respect to their The Yin-Yang of Metabolism; Endometatoxicity (YYME) model (Active NOW), Service to Sheffield University (UK): with respect to Mitochondrial perfect adaptation model (Active NOW), Service to Sanquin (Amsterdam): with respect to Modelling of acute and chronic inflammation (Prospective), Service to Munich (Germany): with respect toCharged peptide to charged membrane binding model (Prospective), Training Hunfeld, EraCoBiotech 2 nd call proposal preparation, ROS detailed model for MSB manucript, Mechanism based modeling viral disease ( COVID-19 ) dynamics in human population, COVID-19 Disease Map, Modelling COVID-19 epidemics, SNAPPER: Synergistic Neurotoxicology APP for Environmental Regulation
Institutions: University of Amsterdam, VU University Amsterdam, Infrastructure Systems Biology Europe, University of Luxembourg, Luxembourg Centre for Systems Biomedicine (LCSB)
I have modelling expertise in precise kinetic models of metabolism and signal transduction; metabolic control analysis, hierarchical regulation analysis, non-equilibrium dynamics, statistical mechanics, enzyme kinetics, flux balance analysis. Energy and carbohydrate metabolism in Archaea, Bacteria and human; ammonium assimilation in Bacteria; differential network-based drug design; cancer metabolic rewiring; cell cycle; genome wide metabolic map and inborn errors of metabolism; epigenetics.
I am research scholar in the Department of Chemical Engineering at the University of Rovira i Virgili, Spain, member of the ENVIRONMENTAL ANALYSIS AND MANAGEMENT (AGA) group and also part of TECNATOX a specialized research center in the area of Technology Transfer in Toxicology, Food and Environmental Health.
MY RESEARCH INTERESTS:
Knowledge Engineering and System modelling in environmental domain. Uncertainty Modelling (Stochastic, Fuzzy and hybrid system) Integrated Modelling and decision ...
Projects: Service to URV Tarragona, Spain with respect to their Safety Assessment of Endocrine Disrupting Chemicals model (Active NOW), EraCoBiotech 2 nd call proposal preparation, SNAPPER: Synergistic Neurotoxicology APP for Environmental Regulation
Institutions: VU University Amsterdam, Universitat Rovira i Virgili
https://orcid.org/0000-0001-9103-9127
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Institutions: Manchester Centre for Integrative Systems Biology, University of Manchester, VU University Amsterdam, University of Amsterdam, Systems Biology Amsterdam
https://orcid.org/0000-0002-0443-6114
Systems Biologist at University of Amsterdam, Free University Amsterdam, University of Manchester, Infrastructure Systems Biology.NL (ISBE.NL), Systems Biology Amsterdam.
ISBE-Light provides M4 service (Make Me My Mode) where non modelers can request (assistance with) the making of a computational model of their biological system. These models are deposited here.
Projects: Service to Milano-Bicocca with respect to their ATP-ROS model (Active NOW), Service to University of Lisbon (Portugal) with respect to their CFTR maturation model (Active NOW), Service to LCSB (Luxembourg) with respect to ROS management in Parkinson’s disease and cancer model (Active NOW), Service to URV Tarragona, Spain with respect to their Safety Assessment of Endocrine Disrupting Chemicals model (Active NOW), Service to Universidade Católica Portugues with respect to their Molecular Insight into Autism Spectrum Disorder (ASD) model (Active NOW), Service to Slovenia with respect to their Protease signaling network in neurodegeneration model (Active NOW), Service to University of Duisburg- Essen (Germany): with respect to their The Yin-Yang of Metabolism; Endometatoxicity (YYME) model (Active NOW), Service to Sheffield University (UK): with respect to Mitochondrial perfect adaptation model (Active NOW), Service to Sanquin (Amsterdam): with respect to Modelling of acute and chronic inflammation (Prospective), Service to Munich (Germany): with respect toCharged peptide to charged membrane binding model (Prospective), Training Hunfeld, EraCoBiotech 2 nd call proposal preparation, ROS detailed model for MSB manucript, Mechanism based modeling viral disease ( COVID-19 ) dynamics in human population
Web page: http://www.isbe.nl
Programme: Model repository for M4 (Make Me My Model) clients of ISBE
Public web page: Not specified
Programme: Model repository for M4 (Make Me My Model) clients of ISBE
Public web page: Not specified
The Integrated Platform for Endocrine Disruptor Risk Assessment (SNAPPER) project will propose solutions based around three core philosophies: Integrated Science: Integration of knowledge from a complete pipeline of systems biology into a holistic yet mechanistic framework that enhances the understanding both of endocrine biology and of adverse effects due to externally induced disruption of the body’s endocrine system. The pipeline includes in vivo, in vitro, and in silico data resulting both ...
Programme: This Project is not associated with a Programme
Public web page: Not specified
Submitter: Alexey Kolodkin
Biological problem addressed: Model Analysis Type
Investigation: ROS networks: designs, aging, Parkinson's disea...
This is a model about a ROS network that exhibits five design principles, and has been calibrated so as to predict quantitatively various steady state concentrations. 10191125.
Instructions RUN the model for steady state. For the Menadione experiment set the initial concentration of 'Menadione' species to experimental dosing i.e. 100 000 nM (0.1 mM) and make the simulation type "reaction" for both the species i.e. 'Menadione' and 'Menadione_internal'. Then run for 24 hr i.e. 1500 minutes approx. ...
Creators: Alexey Kolodkin, Hans V. Westerhoff, Raju Prasad Sharma
Submitter: Alexey Kolodkin
Model type: Ordinary differential equations (ODE)
Model format: Copasi
Environment: Copasi
This is a model about a ROS network that exhibits five design principles, and has been calibrated so as to predict quantitatively various steady state concentrations. 10191125.
Instructions RUN the model for steady state. For the Menadione experiment set the initial concentration of 'Menadione' species to experimental dosing i.e. 100 000 nM (0.1 mM) and make the simulation type "reaction" for both the species i.e. 'Menadione' and 'Menadione_internal'. Then run for 24 hr i.e. 1500 minutes approx. ...
Creators: Hans V. Westerhoff, Raju Prasad Sharma, Alexey Kolodkin
Submitter: Hans V. Westerhoff
Model type: Ordinary differential equations (ODE)
Model format: Copasi
Environment: Copasi
Creator: Alexey Kolodkin
Submitter: Alexey Kolodkin
Model type: Ordinary differential equations (ODE)
Model format: Copasi
Environment: JWS Online
