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3 Publications visible to you, out of a total of 3
Advice from a systems-biology model of the corona epidemics

Abstract (Expand)

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 (iv) it may be best to begin with selecting a lockdown intensity beyond the intensity that leads to the maximum duration, (v) an intermittent lockdown strategy should also work and might be more acceptable socially and economically, (vi) an initially intensive but adaptive lockdown strategy should be most efficient, both in terms of its low number of casualties and shorter duration, (vii) such an adaptive lockdown strategy offers the advantage of being robust to unexpected imports of the virus, e.g. due to international travel, (viii) the eradication strategy may still be superior as it leads to even fewer deaths and a shorter period of economic downturn, but should have the adaptive strategy as backup in case of unexpected infection imports, (ix) earlier detection of infections is the most effective way in which the epidemic can be controlled, whilst waiting for vaccines.

Authors: Hans V. Westerhoff, Alexey N. Kolodkin

Date Published: 1st Dec 2020

Publication Type: Journal

ROS networks: designs, aging, Parkinson's disease and precision therapies.

Abstract (Expand)

How 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.

Authors: A. N Kolodkin, R. P. Sharma, A. M. Colangelo, A. Ignatenko, F. Martorana, D. Jennen, J. J. Briede, N. Brady, M. Barberis, T. D. G. A. Mondeel, M. Papa, V. Kumar, B. Peters, A. Skupin, L. Alberghina, R. Balling, H. V. Westerhoff

Date Published: 26th Oct 2020

Publication Type: Journal

Design principles of ROS dynamic networks relevant to precision therapies for age-related diseases

Abstract (Expand)

The eminently complex regulatory network protecting the cell against oxidative stress, surfaces in several disease maps, including that of Parkinson’s disease (PD). How this molecular networking achieves … its various functionalities and how processes operating at the seconds-minutes time scale cause a disease at a time scale of multiple decennia is enigmatic. By computational analysis, we here disentangle the reactive oxygen species (ROS) regulatory network into a hierarchy of subnetworks that each correspond to a different functionality. The detailed dynamic model of ROS management obtained integrates these functionalities and fits in vitro data sets from two different laboratories. The model shows effective ROS-management for a century, followed by a sudden system’s collapse due to the loss of p62 protein. PD related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the system’s collapse. Various in-silico interventions (e.g. addition of antioxidants or caffeine) slowed down the collapse of the system in silico, suggesting the model may help discover new medicinal and nutritional therapies.

Authors: Alexey Kolodkin, Raju Prasad Sharma, Anna Maria Colangelo, Andrew Ignatenko, Francesca Martorana, Danyel Jennen, Jacco J. Briede, Nathan Brady, Matteo Barberis, Thierry D.G.A. Mondeel, Michele Papa, Vikas Kumar, Bernhard Peters, Alexander Skupin, Lilia Alberghina, Rudi Balling, Hans V. Westerhoff

Date Published: No date defined

Publication Type: Not specified

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