Hans V. Westerhoff

Transcription bursting and stochastics

Using standard systems biology methodologies a 14-compartment dynamic model was developed for the Corona virus epidemic. The model predicts that: (i) it will be impossible to limit lockdown intensity such that sufficient herd immunity develops for this epidemic to die down, (ii) the death toll from the SARS-CoV-2 virus decreases very strongly with increasing intensity of the lockdown, but (iii) the duration of the epidemic increases at first with that intensity and then decreases again, such that ...

This is a project servicing Anna Maria Colangelo of UNIMIB to make models for neural differentiation and the effects of NGF addition and NGF withdrawal

This is the FAIRDOM hub for the Make Me My Model part of ISBE.NL. Various models for ISDBE.NL clients are stored here.

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 ...

Silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

From thermodynamics through kinetics and non equilibrium thermodynamics to control analysis

Chapter on non equilibrium thermodynamics. The chapter discusses both phenomenological and mechanistic non equilibrium thermodynamics. The phenomenological part has as asset compared to earlier treatments that it also considers the phenomenological stoichiometry as a parameter that may be adjusted by systems to attain optimal performance. In the mechanistic part, this feature of variable stoichiometry and 'slips' as well as redistribution of fluxes over parallel branches of metabolism is discussed. ...

A chapter on generalized thermodynamics. The chapter is not specifically about biology although it uses many examples in biology due to the richness of the topic. It deals with the first and second law of thermodynamics, catalysts, and engines. This includes heat engines, heat pumps, and protonmotive ATP synthase.

Most systems biology deals with Life as we know it on this planet (Earth). This project will focus on how (nonsynthetic) Life may differ from mainstream Life. The ultimate focus thereby rests on extraterrestrial Life, but for lack of definitive evidence of this, the project studies Life found under conditions that may be similar to extraterrestrial conditions enabling Life. The focus is herewith on the systems biology in remote environments on Earth. The project deals both with the systems cell ...

Old versions of files that cannot be deleted because they have been published.

Four ppt lecture files that are part of a UvA course on 'How to design an alien'. They correspond to four lectures given by Hans V. Westerhoff, September - October 2021

Modelling COVID-19 epidemics : the training course organized by ISBE-NL, ELIXIR-LU, and EOSC-Life

Glycon proposal preparation

Within the e:Bio - Innovationswettbewerb Systembiologie (Federal Ministry of Education and Research (BMBF)), the SulfoSYSBIOTECH consortium (10 partners), aim to unravel the complexity and regulation of the carbon metabolic network of the thermoacidophilic archaeon Sulfolobus solfataricus (optimal growth at 80°C and pH 3) in order to provide new catalysts ‘extremozymes’ for utilization in White Biotechnology.

Based on the available S. solfataricus genome scale metabolic model (Ulas et al., 2012) ...

Comparative Systems Biology: Lactic Acid Bacteria

Systems analysis of process-induced stresses: towards a quantum increase in process performance of Pseudomonas putida as the cell factory of choice for white biotechnology.

The specific goal of this project is to exploit the full biotechnological efficacy of Pseudomonas putida KT2440 by developing new optimization strategies that increase its performance through a systems biology understanding of key metabolic and regulatory parameters that control callular responses to key stresses generated ...

MOSES (Micro Organism Systems biology: Energy and Saccharomyces cerevisiae) develops a new Systems Biology approach, which is called 'domino systems biology'. It uses this to unravel the role of cellular free energy ('ATP') in the control and regulation of cell function. MOSES operates though continuous iterations between partner groups through a new systems-biology driven data-management workflow. MOSES also tries to serve as a substrate for three or more other SYSMO programs.

Governments and policymakers take different measures vis-à-vis the COVID-19 crisis, ranging from advice to reduce social activities, to a complete lock down of society and economy. To support them with tools that enable them to fulfill their tasks we constructed a differential equation model for the COVID-19 epidemics using systems biology methodologies.

We examined whether such a lockdown could be intermitted with periods with normal social contact, without endangering the success of the strategy.

please add your model here - associated to this assay

To obtain each of the figure 4A - 4D please download "Main Figure 4 Copasi" and open the sub-directory with the name of the sub-figure, run the Copasi files and the time dependence simulation. This will reproduce the figure in this paper.

The first sheet in this excel file is a Table that collects the standard Gibbs energies of formation (from the elements) of a large number of chemical species that are relevant for metabolism. It obtained these from a substantial number of sources, including Thauer et al and Alberty, as indicated at the bottom of the first sheet of the Table. Following Alberty, (2006) the Table also computes the further transformed Gibbs energies of formation, under the standard conditions also used by Alberty, ...

Westerhoff H.V. and Van Dam K. (1987) Thermodynamics and control of biological free-energy transduction, Elsevier, Amsterdam ISBN: 0-444-80783-7 (U.S.)

This monograph gives the basis of both non equilibrium thermodynamics and metabolic control analysis in biology. It is rife with examples from bioenergetics.

It is also a compilation of mathematical equations and text and hence serves as a data file for mathematical biology and biological modelling

working document 31 January 2022 Context is the equilibrium constants measurement standardization

1 file with legends 4 files with figures 2 files with tables

PhD thesis research by Joost W Aerts under supervision of Hans V. Westerhoff, Rob J van Spanning and Pascale Ehrenfreund

In this folder one has the: thesis summary a pdf of the thesis supplemental material per chapter, for chapters 3, 4, 6, and 7

To obtain each of the figure 2A - 2E please download "Main Figure Copasi" and open the sub-directory with the name of the sub-figure, run the Copasi files and the time dependence simulation. This will reproduce the figure in this paper.

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. Plot e.g. ATP.

For H2O2 experimental data validation for repeated treatment at 50uM, 150uM, and 300uM. To run the model with different dosing scenarios, one has to set both the H2O2 initial ...

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. ...

Model building:

The module was built using modular bottom-up approach where every module describes a certain process and then, when modules are connected together like domino tiles, we can reconstruct the emergent behavior of the whole system.

This is a blueprint model and might be used for various country/data. If one wans to use it for a particular country/data, we can recommend following steps:

1. Adjust total population by changing initial condition of A-Initial_population_innocent_non-tested ...

Copasi file chronic inflammation Abulikemu et al 2020 (altered units TNF and MMP8); see supplemntal material: TNF and MMP7 concentration upgrade of the models All computations for the present paper were completed by using the model prepared and tested in Abulikemu et al 2018. Then, little attention was paid to the unit in which concentrations were expressed, except for the concentration of fibroblasts, which we found important for modelling the effect of confluency. This led to a predicted TNF ...

Copasi file chronic inflammation Abulikemu et al 2020 (altered units TNF and MMP8); see supplemntal material: TNF and MMP7 concentration upgrade of the models All computations for the present paper were completed by using the model prepared and tested in Abulikemu et al 2018. Then, little attention was paid to the unit in which concentrations were expressed, except for the concentration of fibroblasts, which we found important for modelling the effect of confluency. This led to a predicted TNF ...

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. ...

Model that can be used to obtain the figures of Abudulikemu et al 2018: Abudukelimu, A., Barberis, M., Redegeld, F.A., Sahin, N., and Westerhoff, H.V. (2018). Predictable Irreversible Switching Between Acute and Chronic Inflammation. Front Immunol 9, 1596.

(Abudulikemu et al 2000 (also 2018) Standard model of acute mode Figure 32.

Particularly figure 2 of of Abudulikemu et al 2020 in press

The principles of Stealthy Engineering (Adamczyk et al.: Biotechnology Journal 2012; 7(7):877-83) are illustrated in this model by emulating a cross engineering intervention between L. lactis and S. cerevisiae.

The case study consists of replacing the native glucose uptake system of L. lactis with that native to the yeast S. cerevisiae. A modified version of Hoefnagel et al.’s model of L. lacrtis’ central metabolism was used as starting point. The total functional replacement of the PTS with the ...

Introductory lecture Biology & Epidemiology

Crash course of Mathematical modelling, for any learners who want to use models to better understand and assess COVID-19 policies around the world! This course aims at anyone who seeks to understand and assess the utility of mathematical models to make a prediction which could play a key role in government policymaking, as well as a research strategy for pandemic diseases such as COVID-19. The strategies of ‘learning by example’ and ‘learning by doing’ will be here instantiated as learning how ...

In this short book written by Hans V. Westerhoff, it is argued that scientific rationality as further developed in systems biology should be used to tackle the complex problems of society. This is promoted as one way to battle the disinformation strategies followed by a great many political leaders with the aim of staying in power through populism.

To be cited as: Westerhoff, H.V., (2020) Trumping the Trumps: Addressing complexities through biological rationality, SysBA press, Amsterdam.

Work document version 31 January 2020

Summary of the PhD thesis by Joost W. Aerts Under the auspices of Rob J. van Spanning, Pascale Ehrenfreund and Hans V. Westerhoff