Sascha Schäuble adminproject_administratorasset_housekeeperprogramme_administrator

Projects: A1, A2, A3, A4 (E), A5, A6, B1, B2, B4, B5, C2, C1, C3, C4 (E), C5, C6 (E), FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, FungiNet C - Candida projects, FungiNet total, INF, Z1, Z2, B3 (E), A7

Institutions: Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

https://orcid.org/0000-0003-3862-6546
Jan Ewald

Projects: B2, FungiNet total, B1

Institutions: Friedrich Schiller University Jena, Department of Bioinformatics, School for Biology and Pharmacy, Julius Maximilians University Würzburg, Biocenter, Department of Bioinformatics

https://orcid.org/0000-0002-9415-2317
Stefan Schuster project_administrator

Projects: FungiNet B - Bioinformatics projects, FungiNet total, B1

Institutions: Friedrich Schiller University Jena, Department of Bioinformatics, School for Biology and Pharmacy

Sybille Dühring

Projects: B1, FungiNet B - Bioinformatics projects, FungiNet total

Institutions: Friedrich Schiller University Jena, Department of Bioinformatics, School for Biology and Pharmacy

Jörg Linde

Projects: FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, FungiNet C - Candida projects, FungiNet total, INF

Institutions: Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

Thomas Dandekar project_administrator

Projects: FungiNet B - Bioinformatics projects, FungiNet total, B1, B2

Institutions: Julius Maximilians University Würzburg, Biocenter, Department of Bioinformatics

Daniela Albrecht-Eckardt

Projects: INF, Z2

Institutions: BioControl Jena GmbH

Christoph Kaleta

Projects: Not specified

Institutions: Not specified

State-based model of whole-blood infection assay with PMN-mediated immune evasion mechanism
B4

This model is a variant of the previously developed SBM of whole-blood infection assay. While in the previous model a spontaneous immune evasion mechanism (A) was implemented in this model immune evasion was caused by PMN molecule secretion (B).

Creators: Teresa Lehnert, Maria T. E. Prauße

Contributor: Sandra Timme

[DEMO] Response of hepatocytes to rapid change in the medium composition (gene regulatory network): Model 1100 "freshMedia"
FungiNet total, FungiNet B - Bioinformatics projects

Primary hepatocytes were exposed to a stimulus by exchanging culture medium, thereby simulating changes in the blood composition. The expression of genes at different time points was recorded. Differentially expressed genes were clustered using fuzzy c-means algorithm into five groups. The arcs of the possible network were identified using the NetGenerator algorithm under the restriction of biological knowledge. The analysis was restricted to the main metabolic pathways of hepatocytes. The reverse
...

Creators: Thomas Wolf, Wolfgang Schmidt-Heck, Reinhard Guthke

Contributor: Thomas Wolf

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Deciphering the Counterplay of Aspergillus fumigatus Infection and Host Inflammation by Evolutionary Games on Graphs.
B4

Abstract (Expand)

Microbial invaders are ubiquitously present and pose the constant risk of infections that are opposed by various defence mechanisms of the human immune system. A tight regulation of the immune response … ensures clearance of microbial invaders and concomitantly limits host damage that is crucial for host viability. To investigate the counterplay of infection and inflammation, we simulated the invasion of the human-pathogenic fungus Aspergillus fumigatus in lung alveoli by evolutionary games on graphs. The layered structure of the innate immune system is represented by a sequence of games in the virtual model. We show that the inflammatory cascade of the immune response is essential for microbial clearance and that the inflammation level correlates with the infection-dose. At low infection-doses, corresponding to daily inhalation of conidia, the resident alveolar macrophages may be sufficient to clear infections, however, at higher infection-doses their primary task shifts towards recruitment of neutrophils to infection sites.

Authors: J. Pollmacher, Sandra Timme, Stefan Schuster, Axel Brakhage, Peter Zipfel, Marc Thilo Figge

Date Published: 13th Jun 2016

Journal: Sci Rep

Deciphering the regulation of metabolism with dynamic optimization: an overview of recent advances.
B2

Abstract (Expand)

Understanding optimality principles shaping the evolution of regulatory networks controlling metabolism is crucial for deriving a holistic picture of how metabolism is integrated into key cellular … processes such as growth, adaptation and pathogenicity. While in the past the focus of research in pathway regulation was mainly based on stationary states, more recently dynamic optimization has proved to be an ideal tool to decipher regulatory strategies for metabolic pathways in response to environmental cues. In this short review, we summarize recent advances in the elucidation of optimal regulatory strategies and identification of optimal control points in metabolic pathways. We discuss biological implications of the discovered optimality principles on genome organization and provide examples how the derived knowledge can be used to identify new treatment strategies against pathogens. Furthermore, we briefly discuss the variety of approaches for solving dynamic optimization problems and emphasize whole-cell resource allocation models as an important emerging area of research that will allow us to study the regulation of metabolism on the whole-cell level.

Authors: Jan Ewald, M. Bartl, Christoph Kaleta

Date Published: 30th Jul 2017

Journal: Biochem Soc Trans

Optimality principles reveal a complex interplay of intermediate toxicity and kinetic efficiency in the regulation of prokaryotic metabolism.
B2

Abstract (Expand)

A precise and rapid adjustment of fluxes through metabolic pathways is crucial for organisms to prevail in changing environmental conditions. Based on this reasoning, many guiding principles that govern … the evolution of metabolic networks and their regulation have been uncovered. To this end, methods from dynamic optimization are ideally suited since they allow to uncover optimality principles behind the regulation of metabolic networks. We used dynamic optimization to investigate the influence of toxic intermediates in connection with the efficiency of enzymes on the regulation of a linear metabolic pathway. Our results predict that transcriptional regulation favors the control of highly efficient enzymes with less toxic upstream intermediates to reduce accumulation of toxic downstream intermediates. We show that the derived optimality principles hold by the analysis of the interplay between intermediate toxicity and pathway regulation in the metabolic pathways of over 5000 sequenced prokaryotes. Moreover, using the lipopolysaccharide biosynthesis in Escherichia coli as an example, we show how knowledge about the relation of regulation, kinetic efficiency and intermediate toxicity can be used to identify drug targets, which control endogenous toxic metabolites and prevent microbial growth. Beyond prokaryotes, we discuss the potential of our findings for the development of antifungal drugs.

Authors: Jan Ewald, M. Bartl, Thomas Dandekar, Christoph Kaleta

Date Published: 18th Feb 2017

Journal: PLoS Comput Biol

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