Dr. Johannes Wollbold

Production of reactive oxygen species (ROS) in the respiratory chain

"I aim at connecting interdisciplinary knowledge in order to understand the logics of free radical production and ageing."

The classical free radical theory of aging assumes that oxidative damage by reactive oxygen species (ROS) accumulates with age in a self-enhancing process. The theory has been confirmed by many experiments in various species. However, it is seriously challenged since several years. In this ambiguous situation, I am collecting and ordering existing knowledge focusing on the questions: Under which conditions do ROS increase with age? Do they always cause damage, or what are beneficial effects? Is a high lifespan observed in spite of a certain level of nonfunctional DNA, proteins or lipids?

In order to shed light on these questions, I developed a specific method of knowledge base construction. Data reported in literature or collected by our experimental partners of the ROSAge consortium is formalized as "Ripple Down Rules" (RDR), a structure of general rules and exceptions. This rule set is further validated and completed by the attribute exploration algorithm [1] of Formal Concept Analysis: Implicational rules proposed by the algorithm are accepted or counterexamples are given, if necessary after supplementary literature or data queries. Thus, a minimal rule base is defined systematically. From this base, all implications valid according to the available knowledge can be derived logically (completeness). I am adapting the open source software conexp-clj (written in the LISP dialect Clojure) accordingly.

Furthermore, my special attention is directed towards physiological conditions where ROS have a positive role for signalling, e.g. in the immune system. Recent findings suggest that - in contrast to other tissues - in inflamed pancreatic acinar cells pro-apoptotic effects of ROS dominate their effect on mitochondrial pore opening leading finally to necrosis

For this situation, we developed a model in multi-valued logic (implemented in R, published 2014 in BMC Systems Biology (see below) and in the BioModels database, after conversion to the SBML-qual standard), based on published data and supplementary measurements by the department of Gastroenterology Rostock. The investigation of beneficial ROS signaling contributes to a more differentiated knowledge of its deregulation and of real ROS influences on ageing. Moreover, we hope to better understand the effect of ROS on enhanced apoptosis as a property of ageing.
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[1] German Wikipedia page co-authored by me, with some English literature and weblinks.