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Christian Luther

About Christian Luther:
No description specified

SEEK ID: https://funginet.hki-jena.de/people/113

Location:  Germany

Expertise: Integrative Data Analysis, Proteomics, Lichtheimia corymbifera, Data Management, protein-protein interaction, Host-Pathogen Interaction, Aspergillus fumigatus, Bioinformatics, Candida albicans

Tools: Python, Java, Phosphoproteomics, Transcriptomics, R, JavaScript, Network analysis, Proteomics, MySQL, PHP

ORCID: Not specified

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Julius Maximilians University Würzburg, Biocenter, Department of Bioinformatics

Country:  Germany

City: 97074 Würzburg

Web page: Not specified

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Comparison of the central human and mouse platelet signaling cascade by systems biological analysis.
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Abstract (Expand)

BACKGROUND: Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein … interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). RESULTS: The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. CONCLUSIONS: Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.

Authors: J. Balkenhol, K. V. Kaltdorf, E. Mammadova-Bach, A. Braun, B. Nieswandt, M. Dittrich, T. Dandekar

Date Published: 22nd Dec 2020

Journal: BMC Genomics

The role of Arabidopsis ABA receptors from the PYR/PYL/RCAR family in stomatal acclimation and closure signal integration.
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Abstract (Expand)

Stomata are microscopic pores found on the surfaces of leaves that act to control CO2 uptake and water loss. By integrating information derived from endogenous signals with cues from the surrounding … environment, the guard cells, which surround the pore, 'set' the stomatal aperture to suit the prevailing conditions. Much research has concentrated on understanding the rapid intracellular changes that result in immediate changes to the stomatal aperture. In this study, we look instead at how stomata acclimate to longer timescale variations in their environment. We show that the closure-inducing signals abscisic acid (ABA), increased CO2, decreased relative air humidity and darkness each access a unique gene network made up of clusters (or modules) of common cellular processes. However, within these networks some gene clusters are shared amongst all four stimuli. All stimuli modulate the expression of members of the PYR/PYL/RCAR family of ABA receptors. However, they are modulated differentially in a stimulus-specific manner. Of the six members of the PYR/PYL/RCAR family expressed in guard cells, PYL2 is sufficient for guard cell ABA-induced responses, whereas in the responses to CO2, PYL4 and PYL5 are essential. Overall, our work shows the importance of ABA as a central regulator and integrator of long-term changes in stomatal behaviour, including sensitivity, elicited by external signals. Understanding this architecture may aid in breeding crops with improved water and nutrient efficiency.

Authors: M. Dittrich, H. M. Mueller, H. Bauer, M. Peirats-Llobet, P. L. Rodriguez, C. M. Geilfus, S. C. Carpentier, K. A. S. Al Rasheid, H. Kollist, E. Merilo, J. Herrmann, T. Muller, P. Ache, A. M. Hetherington, R. Hedrich

Date Published: 28th Aug 2019

Journal: Nat Plants

Analyzing pharmacological intervention points: A method to calculate external stimuli to switch between steady states in regulatory networks.
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Abstract (Expand)

Once biological systems are modeled by regulatory networks, the next step is to include external stimuli, which model the experimental possibilities to affect the activity level of certain network's … nodes, in a mathematical framework. Then, this framework can be interpreted as a mathematical optimal control framework such that optimization algorithms can be used to determine external stimuli which cause a desired switch from an initial state of the network to another final state. These external stimuli are the intervention points for the corresponding biological experiment to obtain the desired outcome of the considered experiment. In this work, the model of regulatory networks is extended to controlled regulatory networks. For this purpose, external stimuli are considered which can affect the activity of the network's nodes by activation or inhibition. A method is presented how to calculate a selection of external stimuli which causes a switch between two different steady states of a regulatory network. A software solution based on Jimena and Mathworks Matlab is provided. Furthermore, numerical examples are presented to demonstrate application and scope of the software on networks of 4 nodes, 11 nodes and 36 nodes. Moreover, we analyze the aggregation of platelets and the behavior of a basic T-helper cell protein-protein interaction network and its maturation towards Th0, Th1, Th2, Th17 and Treg cells in accordance with experimental data.

Authors: T. Breitenbach, C. Liang, N. Beyersdorf, T. Dandekar

Date Published: 17th Jul 2019

Journal: PLoS Comput Biol

Evaluation of Aspergillus and Mucorales specific T-cells and peripheral blood mononuclear cell cytokine signatures as biomarkers of environmental mold exposure.
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Abstract (Expand)

Mold specific T-cells have been described as a supportive biomarker to monitor invasive mycoses and mold exposure. This study comparatively evaluated frequencies and cytokine profiles of Aspergillus … fumigatus and Mucorales reactive T-cells depending on environmental mold exposure. Peripheral blood mononuclear cells (PBMCs) obtained from 35 healthy donors were stimulated with mycelial lysates of A. fumigatus and three human pathogenic Mucorales species. CD154(+) specific T-cells were quantified by flow cytometry. In a second cohort of 20 additional donors, flow cytometry was complemented by 13-plex cytokine assays. Mold exposure of the subjects was determined using a previously established questionnaire. Highly exposed subjects exhibited significantly greater CD154(+)A. fumigatus and Mucorales specific naive and memory T-helper cell frequencies. Significant correlation (r = 0.48 - 0.79) was found between A. fumigatus and Mucorales specific T-cell numbers. Logistic regression analyses revealed that combined analysis of mold specific T-cell frequencies and selected cytokine markers (A. fumigatus: IL-5 and TNF-alpha, R. arrhizus: IL-17A and IL-13) significantly improves classification performance, resulting in 75-90 % predictive power using 10-fold cross-validation. In conclusion, mold specific T-cell frequencies and their cytokine signatures offer promising potential in the assessment of environmental mold exposure. The cytokines identified in this pilot study should be validated in the clinical setting, e. g. in patients with hypersensitivity pneumonitis.

Authors: L. Page, P. Weis, T. Muller, M. Dittrich, M. Lazariotou, M. Dragan, A. M. Waaga-Gasser, J. Helm, T. Dandekar, H. Einsele, J. Loffler, A. J. Ullmann, S. Wurster

Date Published: 12th Sep 2018

Journal: Int J Med Microbiol

Identification of Antifungal Targets Based on Computer Modeling.
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Abstract (Expand)

Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block … enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host(-)pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools.

Authors: E. Bencurova, S. K. Gupta, E. Sarukhanyan, T. Dandekar

Date Published: 4th Jul 2018

Journal: J Fungi (Basel)

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