Stefan Schuster

• Professor
• Friedrich Schiller University Jena

Multiple dangerous pathogens from the World Health Organization’s priority list possess a plethora of virulence components, including the ability to survive inside macrophages. Often, the pathogens rely on a multi-layered defence strategy in order to defend themselves against the immune system. Here, a minimal model is proposed to study such a stra...

Host–pathogen interactions consist of an attack by the pathogen, frequently a defense by the host and possibly a counterdefense by the pathogen. Here, we present a game-theoretical approach to describe such interactions. We consider a game where the host and pathogen are players and can choose between the strategies of defense (or counterdefense) a...

Plants with constitutive defense chemicals exist widely in nature. The phenomenon is backed by abundant data from plant chemical ecology. Sufficient data are also available to conclude that plant defenses act as deterrent and repellent to attacking herbivores, particularly deleterious generalist insects. In the wild, generalist species are usually...

Host-pathogen interactions consist of an attack by the pathogen, frequently a defense by the host and possibly a counter-defense by the pathogen. Here, we present a game-theoretical approach to describing such interactions. We consider a game where the host and pathogen are players and they can choose between the strategies of defense (or counter-d...

Energy metabolism is crucial for all living cells, especially during fast growth or stress scenarios. Many cancer and activated immune cells (Warburg effect) or yeasts (Crabtree effect) mostly rely on aerobic glucose fermentation leading to lactate or ethanol, respectively, to generate ATP. In recent years, several mathematical models have been pro...

Collagens are structural proteins that are predominantly found in the extracellular matrix of multicellular animals, where they are mainly responsible for the stability and structural integrity of various tissues. All collagens contain polypeptide strands (α-chains). There are several types of collagens, some of which differ significantly in form,...

Multiple dangerous pathogens from the World Health Organisation’s priority list possess a plethora of virulence components, including the ability to survive inside macrophages. Often, the pathogens rely on a multi-layered defence strategy in order to defend themselves against the immune system. Here, a minimal model is proposed to study such a stra...

In humans and higher animals, a trade-off between a sufficiently high concentration of erythrocytes (hematocrit), to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. The optimal value lies between the extreme cases of pure blood plasma, which cannot practically transport any oxygen, and...

Mixed-species biofilms of Candida albicans and Staphylococcus aureus pose a significant clinical challenge due to their resistance to the human immune system and antimicrobial therapy. Using evolutionary game theory and nonlinear dynamics, we analyse the complex interactions between these organisms to understand their coexistence in the human host....

Plants store chemical defenses that act as toxins against herbivores, such as toxic isothiocyanates (ITCs) in Brassica plants, hydrolyzed from glucosinolate (GLS) precursors. The fitness of herbivorous larvae can be strongly affected by these toxins, causing immature death. We modeled this phenomenon using a set of ordinary differential equations a...

Knowledge of the frequencies of synonymous triplets in protein-coding and non-coding DNA stretches can be used in gene finding. These frequencies depend on the GC content of the genome or parts of it. An example of interest is provided by stop codons. This is relevant for the definition of Open Reading Frames. A generic case is provided by pseudo-r...

Brassicaceae plants have the glucosinolate–myrosinase defense system, jointly active against herbivory. However, constitutive glucosinolate (GLS) defense is observed to occur at levels that do not deter all insects from feeding. That prompts the question of why Brassicaceae plants have not evolved a higher constitutive defense. The answer may lie i...

A medically important feature of several types of tumors is their ability to “decide” between staying at a primary site in the body or leaving it and forming metastases. The present theoretical study aims to provide a better understanding of the ultimate reasons for this so-called “go-or-grow” dichotomy. To that end, we use game theory, which has p...

Introduction Various herbivorous insects prefer toxic plants as their hosts, although this may appear paradoxical. They have evolved specific adaptations (called counter-defenses) against the toxins. For example, the two-component chemical defense system of plants of the Brassicaceae family against herbivores consists of glucosinolates (GLSs) and t...

Mathematical and computational approaches in chemistry and biochemistry fill a gap in respect to the analysis of the physicochemical features of compounds and their functionality and provide an overview of known as well as yet unknown, but hypothetically possible structures. Nitrogen containing heterocycles such as aziridine, azetidine and pyrrolid...

Plants store chemical defenses that act as toxins to herbivores, such as toxic isothiocyanates (ITCs) in Brassica plants, hydrolyzed from the precursor glucosinolates (GLSs). Fitness of herbivorous larvae can be highly affected by these toxins, causing immature deaths. Theoretically, toxins can inordinately reduce larval fitness to death. We model...

Collagens are structural proteins that are predominantly found in the extracellular matrix, where they are mainly responsible for the stability and structural integrity of various tissues. There are several different types of collagens, some of which differ significantly in form, function, and tissue specificity. Subdivisions into so-called collage...

In the Mathematical Biology community, Reinhart Heinrich (1946-2006) is well-known as one of the founders of Metabolic Control Analysis. Moreover, he made significant contributions on the modelling of erythrocyte metabolism and signal transduction cascades, optimality principles in metabolism, theoretical membrane biophysics and other topics. Here,...

Brassicaceae plants have the glucosinolate-myrosinase defense system, jointly active against herbivory. Glucosinolates (GLS) are hydrolysed by myrosinase to produce isothiocyanates as soon as herbivory begins. Isothiocyanates exert detrimental effects on the feeding insects. However, constitutive GLS defense is observed to occur at levels that do n...

Various herbivorous insects prefer plants of the Brassicaceae family as their hosts, although they are toxic. The two-component chemical defence system of the Brassicaceae against herbivores consists of glucosinolates (GLS) and the activating enzyme myrosinase. GLS hydrolysis by myrosinase leads to isothiocyanate (ITC) products, which are toxic and...

A coiled coil is a structural motif in proteins that consists of at least two α-helices wound around each other. For structural stabilization, these α-helices form interhelical contacts via their amino acid side chains. However, there are restrictions as to the distances along the amino acid sequence at which those contacts occur. As the spatial pe...

Iron-reducing and iron-oxidizing bacteria are of interest in a variety of environmental and industrial applications. Such bacteria often co-occur at oxic-anoxic gradients in aquatic and terrestrial habitats. In this paper, we present the first computational agent-based model of microbial iron cycling, between the anaerobic ferric iron (Fe ³⁺ )-redu...

Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system an...

The burden of fungal infections for humans, animals and plants is widely underestimated and comprises deadly infections as well as great conomic costs. Despite that, antifungal drugs are scarce and emergence of resistance in fungal strains contributes to a high mortality. To overcome this shortage, we propose toxic intermediates and their controlli...

Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system an...

In this review, we summarize and briefly discuss various approaches to modeling the metabolism in human immune cells, with a focus on energy metabolism. These approaches include metabolic reconstruction, elementary modes, and flux balance analysis, which are often subsumed under constraint-based modeling. Further approaches are evolutionary game th...

Aging research is a very popular field of research in which the deterioration or decline of various physiological features is studied. Here we consider the molecular level, which can also have effects on the macroscopic level. The proteinogenic amino acids differ in their susceptibilities to non-enzymatic modification. Some of these modifications c...

In humans and higher animals, a trade-off between sufficiently high erythrocyte concentrations to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. Optimal hematocrit theory has been successful in predicting hematocrit (HCT) values of about 0.3–0.5, in very good agreement with the normal...

Most unicellular organisms live in communities and express different phenotypes. Many efforts have been made to study the population dynamics of such complex communities of cells, coexisting as well-coordinated units. Minimal models based on ordinary differential equations are powerful tools that can help us understand complex phenomena. They repre...

The classification of proteinogenic amino acids is crucial for understanding their commonalities as well as their differences to provide a hint for why life settled on the usage of precisely those amino acids. It is also crucial for predicting electrostatic, hydrophobic, stacking and other interactions, for assessing conservation in multiple alignm...

Understanding the process of aging is still an important challenge to enable healthy aging and to prevent age-related diseases. Most studies in age research investigate the decline in organ functionality and gene activity with age. The focus on decline can even be considered a paradigm in that field. However, there are certain aspects that remain s...

Biofilms are composed of microorganisms attached to a solid surface or floating on top of a liquid surface. They pose challenges in the field of medicine but can also have useful applications in industry. Regulation of biofilm growth is complex and still largely elusive. Oscillations are thought to be advantageous for biofilms to cope with nutrient...

Biofilms offer an excellent example of ecological interaction among bacteria. Temporal and spatial oscillations in biofilms are an emerging topic. In this paper, we describe the metabolic oscillations in Bacillus subtilis biofilms by applying the smallest theoretical chemical reaction system showing Hopf bifurcation proposed by Wilhelm and Heinrich...

Pathogenic microorganisms entail enormous problems for humans, livestock, and crop plants. A better understanding of the different infection strategies of the pathogens enables us to derive optimal treatments to mitigate infectious diseases or develop vaccinations preventing the occurrence of infections altogether. In this review, we highlight the...

In host-pathogen interactions, often the host (attacked organism) defends itself by some toxic compound and the parasite, in turn, responds by producing an enzyme that inactivates that compound. In some cases, the host can respond by producing an inhibitor of that enzyme, which can be considered as a counter-counter defence. An example is provided...

In host-pathogen interactions, often the host (attacked organism) defends itself by some toxic compound and the parasite, in turn, responds by producing an enzyme that inactivates that compound. In some cases, the host can respond by producing an inhibitor of that enzyme, which can be considered as a counter-counter defence. An example is provided...

The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale. These errors have been co...

Molecular mimicry is the formation of specific molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show such a behaviour by utilizing human complement factor H to hide in the blood stream. We call this type of mimicry molecular crypsis. Such a crypsis can re...

C3b active hemispheric region. (PDF)

Opsonization states and relevant complement factor concentrations without the scaling factor accounting for spatial effects. (PDF)

Opsonization states and relevant complement factor concentrations with higher heparan sulfate concentration and lower Pra1 concentration on the surfaces. (PDF)

Example dynamics assuming no inflow of C3 and FH. (PDF)

Complement protein concentrations used in the model. (PDF)

C3b diffusion in the blood. (PDF)

Scaling factor for the affinity of surface derived nascent C3b to the originating surface. (PDF)

Supporting references. (PDF)

Diagram of all reactions occurring in the C. albicans model. (PDF)

Example dynamics assuming inflow of C3 and FH limited only by blood flow. (PDF)

Opsonization states and relevant complement factor concentrations assuming unlimited inflow of C3 and FH. (PDF)

Binding rate of reactive C3b. (PDF)

Surface area distributions and erythrocyte count distribution used for sampling. (PDF)

Opsonization states and relevant complement factor concentrations assuming inflow of C3 and FH limited only by blood flow. (PDF)

Opsonization states and relevant complement factor concentrations assuming no inflow of C3 and FH. (PDF)

Kinetic rate constants used in the model. (PDF)

Decay rate of reactive C3b. (PDF)

Inflow and outflow of relevant complement factors C3 and H in the blood stream. (PDF)

The complete ODE model. (PDF)

Microorganisms encounter a diversity of chemical stimuli that trigger individual responses and influence population dynamics. However, microbial behavior under the influence of different incentives and microbial decision-making is poorly understood. Benthic marine diatoms that react to sexual attractants as well as to nutrient gradients face such m...

This supplement provides a detailed description of the metabolic model and the process of parameter calibration, as well as the sensitivity analysis and parameter scan result.

Mikroalgenbasierte Substanzen erlangen zunehmend Bedeutung als Bestandteil funktioneller Lebensmittel bzw. Nutrazeutika. Mikroalgen der Gattung Nannochloropsis zeichnet vor allem ein hoher Gehalt an der mehrfach ungesättigten ω-3-Fettsäure Eicosapentaensäure (EPA) als Wertstoff aus. Spezies-unabhängig sind mikroalgenbasierte Wertstoffe häufig in Ze...

Molecular mimicry is the formation of specific molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show such a behaviour by utilizing human complement factor H to hide in the blood stream. We call this type of mimicry molecular crypsis. Such a crypsis can re...

As a part of the complement system, factor H regulates phagocytosis and helps differentiate between a body's own and foreign cells. Owing to mimicry efforts, some pathogenic microorganisms such as Candida albicans are able to bind factor H on their cell surfaces and, thus, become similar to host cells. This implies that the decision between self an...

Many differentiated cells rely primarily on mitochondrial oxidative phosphorylation for generating energy in the form of ATP needed for cellular metabolism. In contrast most tumor cells instead rely on aerobic glycolysis leading to lactate to about the same extent as on respiration. Warburg found that cancer cells to support oxidative phosphorylati...

Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing base...

The identification of disease-associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. However, their identification is hampered by the detection of protein communities within large-scale, whole-genome PPINs. A presented successful st...

Gegenwärtig besteht ein wachsendes Interesse an der ökonomischen Produktion algenbasierter Inhaltsstoffe für nutrazeutische, kosmetische und pharmazeutische Erzeugnisse. Mikroalgen der Gattung Nannochloropsis zeichnet u.a. ein hoher Gehalt an der mehrfach ungesättigten ω-3-Fettsäure Eicosapentaensäure (EPA) als Wertstoff aus. Im Hinblick auf eine e...

Intrinsic of non-alcoholic fatty liver diseases is an aberrant accumulation of triglycerides (steatosis), which occurs inhomogeneously within lobules. To improve our understanding of the mechanisms involved in this zonation patterning, we developed a mathematical multicompartment model of hepatic fatty acid metabolism accompanied by blood flow simu...

The release of fungal cells following macrophage phagocytosis, called non-lytic expulsion, is reported for several fungal pathogens. On one hand, non-lytic expulsion may benefit the fungus in escaping the microbicidal environment of the phagosome. On the other hand, the macrophage could profit in terms of avoiding its own lysis and being able to un...

Die ökonomische Kultivierung von Mikroalgen erfordert u. a. eine Bioprozess-auslegung hinsichtlich maximaler Biomasseproduktivität. Dafür ist im kontinuierlichen Bioprozess die Einhaltung des optimalen Betriebspunktes essenziell. In Experimenten wurde die nächtliche Biomasse-Abnahme untersucht, welche zu einer deutlichen Verschiebung des Betriebspu...

The identification of disease associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. A major problem hampering their identification is the detection of protein communities within large-scale, whole-genome PPINs. Current strategies s...

Sexual communication between complementary mating partners in the fungal group of zygomycetes is mediated by the trisporoid pheromone system. A key enzyme towards biosynthesis of hormonally active trisporoids is 4-dihydromethyltrisporate dehydrogenase (TSP1), an enzyme occurring in all zygomycetous fungi. Trisporic acid and some of its precursor mo...

Biomass productivity of large-scale continuous algal cultures is highly dependent on the choice of the operating point. Besides the optimal lighting of algal cultures, the dark cycle biomass decline due to respiration and/or decay is, although often overlooked, an important factor to ensure maximal productivity. The hypothesis of immediate and ongo...

Table of state variables and parameters. (PDF)

UML of CELL-ABC representing the order of the main simulation processes. Diagram of the basic processes and procedures of CELL-ABC model. (TIF)

Simulated genotype fractions at different grid dimensions and durations of simulation runs. Fractions of simulated genotypes after (A) 100 simulation steps using grids of different dimensions (n = 15) or (B) on a grid with the dimensions 100x100 grid cells after simulations of a different duration (n = 15). Both parameters were varied to identify t...

Population dynamics in environments with amino acid supplementation. Repeated simulations (n = 100) are plotted for varying benefit-to-cost ratios (BCR) and degrees of amino acid diffusion (bold line: mean, shaded ribbon: standard deviation). All simulations start with a random distribution of all genotypes and undergo a specific dynamic alternatio...

Laboratory experiments. (PDF)

Varying initial fraction of cross-feeding genotypes. Repeated simulations (n = 200) are plotted for varying initial fractions (5% to 95%) of cross-feeding genotypes (i.e. CF1 and CF2) in the community. Simulations were run for low (A and C) and high (B and D) diffusion conditions, both in the absence (A and B) and presence (C and D) of an environme...

Experimentally determined growth parameters of all six genotypes. A Monod kinetic was fitted to the growth of all genotypes. Based on this, the growth parameters (A) Vmax and (B) KM were determined for wild type (WT), the overproducer (Δmdh, OP), the arginine auxotroph (ΔargH, AUX 1), the leucine auxotroph (ΔleuB, AUX 2), as well as the two cross-f...

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 i...

We present a genome-scale model of Caenorhabditis elegans metabolism along with the public database ElegCyc (http://elegcyc.bioinf.uni-jena.de:1100), which represents a reference for metabolic pathways in the worm and allows for the visualization as well as analysis of omics datasets. Our model reflects the metabolic peculiarities of C. elegans tha...

Horizontal gene transfer (HGT) is a widespread phenomenon, not only in prokaryotes. Protozoa are especially prone to HGT, as many of them live together with other organisms in close endosymbiotic relationship. Detection of horizontal gene transfer can be a difficult task, especially for transfer events from prokaryotes to eukaryotes, if species are...