Systems Biology of Microbial Communities

Metabolism-centered Predictive Modeling of Anaerobic Digestion for Biogas Production (McBiogas)

McBiogas Logo
McBiogas
Photo: Sebastian Wiedling

Research Topic

Microorganisms typically occur as highly divers communities in nature. This allows for a multiude of interactions to occur between members of the community and makes complex transformation processes possible. Anaerobic digestion is a typically example for such a community-driven process in which organic material is transformed to methane. To optimally control this process in biogas plants, mathematical models have been developed. These models, however, typically only consider major process steps und do not directly consider the high phenotypic diversity of involved communities. Both their composition and activity can today be assessed with high accuracy by culture-independent methods including metagenomics, metatranscriptomics, and metaproteomics. Our aim is to use such data to create mathematical models detailing the metabolic transformation network within microbial communities. Towards this end, species-specific metabolic network models are inferred and coupled to a dynamic community model following the dynamic Flux-Balance-Analysis approach. Due to their predictive power, such models will be used to early detect looming process breakdowns and to initiate proper counter measures, as well as to explore the potential for flexibel on-demand biogas production.

Following a Systems Biology approach, the McBiogas project requires the close interdisciplinary cooperation between experimental and theoretical work. We use lab-scale biogas reactors as our experimental system, develop bioinformatic methods for the inference of metabolic network models, and design and implement modeling software for the simulation of microbial communities.

PhD students

Daniela Becker (née Taraba)

Rodrigo Amarante Colpo

Undergraduates

Florian Schmidt

Jia Fu

 

Interns

James Shields



Experimental Biogas Research

We run lab-scale biogas reactors to study selected aspects of biogas production. Besides standard process analytics, we assess microbial community dynamics via metagenomics, metatrancriptomics, metaproteomics, flowcytometry, and microcalorimetry.

Contact:
Denny Popp, Daniela Taraba, Florian Centler
Partner:
Sabine Kleinsteuber, Heike Sträuber, Thomas Maskow, Martin von Bergen, Nico Jehmlich, Susann Müller

Modeling Microbial Communities

We develop mathematical models describing the dynamics of microbial communities, focussing on metabolic transformation processes. Both ordinary-differentail-equation-based and Flux-Balance-Analysis approaches, and combinations of both, are used.
Contact:
Florian Centler, Denny Popp
Partner:
Steffen Klamt (MPI Magdeburg), Sabine Koch (MPI Magdeburg), Dirk Benndorf (Uni Magdeburg), Sören Weinrich (DBFZ)

Spatio-temporal Modeling

Space plays an essential role for natural microbial systems. Within the TWIN-Project, we develop experimental systems and spatio-temporal models for studying functional stability and resilience. Individual-based modeling approaches are used for analyzing bacteria-bacteria and bacteria-fungi interactions.
Ansprechpartner:
Florian Centler
Kooperationspartner:
Lukas Wick, Martin Thullner, Karin Frank, Thomas Banitz, Sara König, Tom Berthold, Matthias Kästner, Anja Miltner, Anja Worrich

Network analysis of microbial communities

Spatial and temporal data on microbial community composition can provide evidence for principles of the organization of microbial life. The complex interplay at work can be visualized by co-occurrence analysis-derived networks, which can be explored by methods from network analysis and data-mining.
Ansprechpartner:
Florian Centler
Kooperationspartner:
Annelie Wendeberg, Annelie Steinbach, Torsten Jeske, Lukas Wick, Michael Schloter (Helmholtz-Zentrum München)

In Silico Metabolic Engineering

Details under "M.Sc. topics" below.

Ecological Stability Properties

In colaboration with our flow cytometry experts, we developed an R-script that assesses a microbial community's response to a disturbance over time, computing numerical values for resistance and resilience, among other stability properties. Developed with flow cytometric data in mind, it is equally applicable to any OMICS data which provides relative abundance time series data. Read more in our open access publication. Get the script at GitHub.


Community evolution and tracking its distance to the initial reference state.
Evolution of community composition, starting from a reference state (red circle, left), and following its deviation from this reference state over time (right).

Infering Interaction Networks

Data on microbial community structure and its evolution over time are routinely recorded today. Can such data be used to infer microbial interactions? We developed an R package that takes such data and fits interaction matrices of generalized Lotka-Volterra models. Additionally, the package allows for the generation of in silico data with known interactions to assess the correctness of inferred interaction networks.

Get the R package at GitHub.



Fitting a gLV model to experimental data, and visualizing the inferred interaction network
Fitting an generalized Lotka-Volterra model (lines) to experimental data (symbols, left), and visualization of inferred interaction network (right).

Reactive Flow and Transport Simulator

Details can be found here.

2019

Denny Popp, Florian Centler. µbialSim: constraint-based dynamic simulation of complex microbiomes. bioRxiv doi: 10.1101/716126

Sören Weinrich, Sabine Koch, Fabian Bonk, Denny Popp, Dirk Benndorf, Steffen Klamt, Florian Centler. Augmenting biogas process modeling by resolving intracellular metabolic activity. Frontiers in Microbiology 2019 10:1095 doi: 10.3389/fmicb.2019.01095

Fabian Bonk, Denny Popp, Sören Weinrich, Heike Sträuber, Daniela Becker, Sabine Kleinsteuber, Hauke Harms, Florian Centler. Determination of Microbial Maintenance in Acetogenesis and Methanogenesis by Experimental and Modeling Techniques. Frontiers in Microbiology. 2019 10:166 doi: 10.3389/fmicb.2019.00166

2018

Fabian Bonk, Denny Popp, Sören Weinrich, Heike Sträuber, Sabine Kleinsteuber, Hauke Harms, Florian Centler. Ammonia inhibition of anaerobic volatile fatty acid degrading microbial communities. Frontiers in Microbiology. 2018 9:2921 doi: 10.3389/fmicb.2018.02921

Fabian Bonk, Denny Popp, Sören Weinrich, Heike Sträuber, Sabine Kleinsteuber, Hauke Harms, Florian Centler. Intermittent fasting for microbes: how discontinuous feeding increases functional stability in anaerobic digestion. Biotechnology for Biofuels 2018 11:274 doi: 10.1186/s13068-018-1279-5

Fabian Bonk*, Denny Popp*, Hauke Harms, Florian Centler. PCR-based quantification of taxa-specific abundances in microbial communities: Quantifying and avoiding common pitfalls. Journal of Microbiological Methods. 2018 153:139-147 doi: 10.1016/j.mimet.2018.09.015 (*contributed equally)
Courses offered by our group:

HIGRADE course Introduction to Systems Biology: From OMICS data analysis to metabolic network modeling.

    The next course will be in autumn 2019.

Develop course Introduction to long read sequencing for (meta)genomics.

    The next course will be on 16th of January 2020.

Details available at the HIGRADE website.


Further contributions to teaching activities:

HIGRADE course Fluxomics - Quantifying the Metabolic Phenotype (Florian Centler)

TU Dresden Continuous Bioprocesses: Anaerobic Digestion - Lecture and exercise (winter semester - Denny Popp)

University Leipzig Quantitative Biology for a sustainable enrivonmental and industrial biotechnology - Several lectures and exercise (sommer semester - Florian Centler, Denny Popp)


Alumni

PhD students: Fabian Bonk

Master students: Anna Weimer, Marting Graf, Sebastian Luhnburg, Eric Witt, Stephanie Otto, Sophia Klink, Tatjana Malycheva, Stefan Bauer, Paul Jähne, Lukas Hirsch

Bachelor students: Robin Goldmann, Eric Witt

Interns: Salomé Herbin, Emine Ceren Özveri, Hamna Saleem, Piotr Jachimowicz, Amit Nain, Ahmad Zino

Student assistants: Tarek M.M. Hamed Elzamel, Vivien Wieczorek, Athaydes Francisco Leite, Daniela Pietzsch, Malte Stadtmann, Josephine Hörner, Nicole Thiemich

Mcbiogas for the win
McBiogas and his team won the poster slam at the 3rd International Conference on Monitoring and Process Control of Anaerobic Digestion Plants! (c) DBFZ

  • Outstanding Poster Award - 15th IWA World Conference on Anaerobic Digestion (AD15-2017), October 2017, Beijing, China
  • Young Investigator Group Award - e:Bio Status Seminar 2017 BMBF, September 2017, Dresden, Germany
  • Best Poster Pitch - HIGRADE Conference 2017, May 2017, Leipzig, Germany
  • Best Poster Prize - 3rd International Conference on Biogas Microbiology (ICBM3), May 2017, Wageningen, The Netherlands
  • Best Poster Slam - 3rd International Conference on Monitoring and Process Control of Anaerobic Digestion Plants, March 2017, Leipzig, Germany

Open topics

We are offering research topics in the area of mathematical modeling, analysis of microbial communities and biogas reactor experiments. Please contact us if you are interested in the simulation of metabolic networks, network analysis, indiviudal-based modeling, or the development of bioinformatic tools. Besides theoretical topics, wet lab related topics are also available, find more details here.

Contact


Current topics

Master thesis: "Metabolic network reconstruction of microorganisms found in biogas reactors and community-wide flux balance analysis" Jia Fu, Leipzig University

Metabolic network will be reconstructed from metagenome assembled genomes (MAGs) from biogas reactors. Flux balance analysis will be performed of the inidividual as well as community-wide metabolic networks.

Master thesis: "Meta analysis of bacterial communities in biogas processes" Florian Schmidt, Leipzig University

The bacterial communities facilitating the biogas production are described in hundreds of publication. A meta analysis on these community descriptions will be performed to elucidate typcial community structures.


Completed topics

2019

Anna Weimer: "Anaerobic degradation of volatile fatty acids in continuous biogas reactors at very short hydraulic retention times" master thesis, University of Lund, Sweden

Martin Graf: "Integrated analysis of compositional multiomics time series data for the discovery of microbial interactions and metabolic networks" master thesis, Osnabrück University

Sebastian Luhnburg: "Characterization of microbical communities by combined analysis of flow cytometry and amplicon sequencing data", master thesis, Leipzig University

2018

Eric Witt: "Creation of metabolic network models from genome data", master thesis, Leipzig University

Stephanie Otto: "Anaerobic degradation of volatile fatty acids in biogas reactors at very short hydraulic retention times", master thesis, Hochschule für angewandte Wissenschaft und Kunst Hildesheim/Holzminden/Göttingen University of Applied Sciences and Arts

Tatjana Malycheva: "Anaaerobic digestion of propionic acid: Dynamics of microbial communities and kinetics of propionic acid oxidation", master thesis, Saarland University

Sophia Klink: "Molecular biological analysis of biogas reactors under ammonia inhibition", master thesis, Ludwig Maximilian University of Munich

2017

Stefan Bauer: "Comparison of methods for quantification of biomass from a biogas reactor", master thesis, University of Kassel

Robin Goldmann: "Molecular biological analysis of microbial communities in biogas reactors", bachelor thesis, Leipzig University

2016

Paul Jähne: "Optimization of in silico metabolic engineering strategies with evolutionary algorithm using CUDA", master thesis, Leipzig University of Applied Sciences

Lukas Hirsch: "Using dynamic modeling to infer microbial interaction networks from flow cytometry data", master thesis, Leipzig University

Eric Witt: "Molecularbiological characterization of microbial communities in biogas reactors", bachelor thesis (in cooperation with the group Microbiology of Anaerobic Systems), Leipzig University


Funding

This group is funded by the BMBF.

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