Flow Cytometry

Flow Cytometry

Research Topics

The general topic of our multidisciplinary group (biochemists, biotechnologists, bioinformaticians) is to study life strategies of microbial populations and communities. Most microbial analyses are realized by measuring average properties of bulk data. However, we exploit high-troughput multi-parameter flow cytometry to obtain single cell data and use them for understanding and optimisation of biotechnological and environmental processes. With our methods we are able to provide information about individual cell characteristics along with structural and functional parameters. Fast dynamics can be analysed and resulting variation in community structure can be quantified and calculated. We developed bioinformatic tools to detect community variation almost immediately and use these tool to develop process strategies in order to stabilize complex microbial processes in managed systems like biogas production and wastewater treatment. Ecosystems analyses can also be performed on the single cell  level (groundwater, soil). Heterogeneity of cells in clonal cultures is another focus of our research. Here, specific cell chacateristics like growth, viability, productivity or plasmid stability are some of our research targets.

Topics of research are:

  • Analysis of the diversity and stability of performances of microbial populations in natural and artificial habitats. Information is available about stability of proportional constant proliferation of microbial populations within consortia cooperating in the detoxification and mineralization of xenobiotics.
  • The impact of toxic compounds on cell behaviour and viability including information on the energy providing system (membrane potential) and membrane integrity (fluidity).
  • The development of off- and on-line strategies for biotechnological processes. Microorganisms act as biological catalytical systems which perform the synthesis or the refinement of distinct products. Unlike chemical catalysts in chemistry the efficiency of microorganisms depends on their physiological status. As a consequence such information is used to control established industrial biotechnological processes as well as scarcely developed lab-scale processes. Our group has a long standing experience in optimising brewing processes and developing strategies for product production by bacteria.

AG Flow Cytometry

Bioinformatic Tools

Natural microbial systems are highly dynamic due to the short generation times of the comprised organisms and their rapid and distinct reactions to changing environments. Microbial flow cytometry approaches are capable techniques for following such community dynamics in a fast and inexpensive way. Newly developed bioinformatics tools not only enable quantification of single cell dynamics, they also make nearly on-line evaluation of community attributes possible, enable interpretation of community trends, and reveal possible constraints that influence community structure and function. Microbial flow cytometry is poised to make the microbial cytome accessible for ambitious ecosystem studies. Functions of cells within the cytome can be determined either by cell sorting in combination with other -omics.

Cytometric fingerprints for monitoring microbial community dynamics can be analyzed with the following tools:

Dalmatian Plot
Cytometric Histogram Image Comparison (CHIC)
Cytometric Barcoding (CyBar)

Current research

Zentrales Innovationsprogramm Mittelstand (ZIM) des BMWi – Kooperationsnetzwerke, Aktenzeichen: 16KN043222, ABOS – Entwicklung einer Abfall-Biogas-Online-Steuerung zur effektiven Überwachung des Vergärungsprozesses, Teilprojekt UFZ: ABOS – Prozesssimulation: 170 K€
(responsible: Susann Müller)

BMBF: Bundeshaushalt, Einzelplan 30, Kapitel 3005, Titel 68330
Aktenzeichen: 031A616K, Wissensbasierte Prozessintelligenz – Neue Wege zu stabilen Bioprozessen, Teilprojekt K, Total: 20 Mio
Partec/Sysmex in Parterschaft mit UFZ: 193 k€
(responsible: Sysmex/Partec)

BMEL-FNR: Förderschwerpunkt: Mikrobiologische Prozesse in Biogasanlagen, Aktenzeichen: 22008313, BiogasFingerprint-Flexible Steuerung der Biogasproduktion mittels bioinformatischer Populationsanalyse (Biogas-Fingerprint)
(responsible. Susann Müller), Total: UFZ: 364 k€

Deutsche Bundestiftung Umwelt (DBU), Aktenzeichen:33960/01-32
On-demand Produktion von Phosphatdünger aus Reststoffen von Brauerei und Kläranlage (Bio-P2)
(responsible: Susann Müller), Total: 692.516 K€

Chinese Scholarship Council (CSC), China, Ministery of Education
‘Development of stable performance of microbial communities in wastewater treatment systems’
(responsible: Susann Müller)

Chinese Scholarship Council (CSC), China, Ministery of Education
‘Natural microbial communities (NMC) for product synthesis – Conditions and options for their control’
(responsible: Susann Müller)

Selected Publications

Guo Y, Cichocki N, Schattenberg F, Geffers R, Harms H, Müller S
AgNPs change microbial community structures of wastewater.
Frontiers in Microbiology (2019) Vol9, 3211

Liu Z, Cichocki N, Hübschmann T, Süring C, Ofiţeru ID, Sloan WT, Grimm V, Müller S
Neutral mechanisms and niche differentiation in steady-state insular microbial communities revealed by single cell analysis.
Environmental Microbiology (2018),  doi:10.1111/1462-2920.14437

Lambrecht J, Schattenberg F, Harms H, Müller S.
Characterizing microbiome dynamics – flow cytometry based workflows from pure cultures to natural communities.
Journal of Visualized Experiment (2018) 137, e58033

Liu Z, Cichocki N, Bonk F, Günther S, Schattenberg F, Harms H, Centler F, Müller S. Ecological stability properties of microbial communities assessed by flow cytometry.
mSphere (2018), 3/1, e00564-17

Koch C, Müller S. Personalized microbiome dynamics – Cytometric fingerprints for routine
Molecular Aspects of Medicine (2018), 59, 123-134

van Gelder S, Röhrig N, Schattenberg F, Cichocki N, Schumann J, Schmalz G, Haak R, Ziebolz D, Müller S.
A cytometric approach to follow variation and dynamics of the salivary microbiota
Methods (2018) 134-135:67-79

Lambrecht J, Cichocki N, Hübschmann T, Koch C, Harms H, Müller S.
Flow cytometric quantification, sorting and sequencing of methanogenic archaea based on F420 autofluorescence.
Microbial Cell Factories (2017) 16:180.

Guo Y, Baumgart S, Stärk HJ, Harms H, Müller S.
Mass cytometry for detection of silver at the bacterial single cell level
Front. Microbiol. (2017) 8:1326.

Guo Y, Stärk HJ, Harms H, Wick LY, Müller S.
Heterogenic response of prokaryotes towards silver nanoparticles and ions.
Cytometry Part A (2017) 91(8), 775-784

Cossarizza, A., Chang, H.-D., Radbruch, A., Akdis, M., Andrä, I., Annunziato, F., Bacher, P., Barnaba, V., Battistini, L., Bauer, W.M., Baumgart, S., Becher, B., Beisker, W., Berek, C., Blanco, A., Borsellino, G., Boulais, P.E., Brinkman, R.R., Büscher, M., Busch, D.H., Bushnell, T.P., Cao, X., Cavani, A., Chattopadhyay, P.K., Cheng, Q., Chow, S., Clerici, M., Cooke, A., Cosma, A., Cosmi, L., Cumano, A., Dang, V.D., Davies, D., De Biasi, S., Del Zotto, G., Müller, S., Müller, W., et al.,
Guidelines for the use of flow cytometry and cell sorting in immunological studies
European Journal of Immunology (2017) 47:10, 1584 - 1797

Berthold T, Centler F, Hübschmann T, Remer R, Thullner M, Harms H, Wick LY.
Mycelia as a focal point for horizontal gene transfer among soil bacteria.
Scientific Reports (2016) 6:36390.

Günher S, Faust K, Schumann, J, Harms H, Raes, J, Müller S.
Species-sorting and mass-transfer paradigms control managed natural metacommunities.
Environmental Microbiology (2016) 18(12):4862-4877.

Zimmermann J, Hübschmann T, Schattenberg F, Schumann J, Durek P, Riedel R, Friedrich M, Glauben R, Siegmund B, Radbruch A, Müller S, Dong HD
High-resolution Microbiota flow cytometry reveals dynamic colitis-associated changes in fecal bacterial composition.
European Journal of Immunology (2016) 46, 1300-1303.

Lieder S, Jahn M, Koepff J, Müller S, Takors R
Stress speeds up DNA replication in Pseudomonas putida in chemostat cultivations
Biotechnology Journal (2016), 11, 155-163

Jahn M, Günther S, Müller S
Non-random distribution of macromolecules as driving forces for phenotypic variation
Current Opinion Microbiology (2015) 25, 49-55.

Koch C, Harnisch F, Schröder U and Müller S
Cytometric fingerprints: evaluation of new tools for analyzing microbial community dynamics
Frontiers in Microbiology Section Systems Microbiology 2014, Vol. 5 Article 273, 1-11.

Jahn M, Vorpahl C, Türkowsky D, Lindmeyer M, Bühler B, Harms H, Müller S
Accurate Determination of Plasmid Copy Number of Flow-Sorted Cells using Droplet Digital PCR
Analytical Chemistry (2014) 86 5969-5976.

Koch C, Harms H, Müller S
Dynamics in the microbial cytome – single cell analytics in natural systems
Current Opinion Biotechnology (2014) 27 134-141.

Koch C, Müller S, Harms H, Harnisch F
Microbiomes in bioenergy production: From analysis to management
Current Opinion Biotechnology (2014) 27, 65-72.

Koch C, Fetzer I, Schmidt T, Harms H, Müller S
Monitoring functions in managed microbial systems by cytometric bar coding
Environmental Science and Technology (2013) 47, 1753-1760

Jahn M, Seifert J, von Bergen M, Schmid A, Bühler B, Müller S
Subpopulation-proteomics in prokaryotic populations
Current Opinion Biotechnology (2013) 24, 79-87.

Koch C, Günther S, Desta AF, Hübschmann T, Müller S
Cytometric fingerprinting for analysing microbial intra-community structure variation and identifying sub-community function
Nature Protocols (2013) 8/1, 190-202.

Günther S, Koch C, Hübschmann T, Röske I, Müller RA, Bley T, Harms H, Müller S
Correlation of community dynamics and process parameters as a tool for the prediction of the stability of wastewater treatment.
Environmental Science and Technology (2012) 46(1), 84-92.

Harnisch F, Koch C, Patil SA, Hübschmann T, Müller S, Schröder U
Revealing the electrochemically driven selection in natural community derived microbial biofilms using flow–cytometry
Energy & Environmental Science (2011) 4 (4) 1265 – 1267.

Müller S and Nebe-von-Caron G
Functional single-cell analyses – flow cytometry and cell sorting of microbial populations and communities.
FEMS Microbiol Rev (2010) 34, 554–587.

Müller, S.
Modes of cytometric bacterial DNA pattern – A tool for pursuing growth
Cell Proliferation (2007) 40, 621-635.

Achilles J., Stahl F., Harms H., Müller S.
Isolation of intact RNA from cytometrically sorted S. cerevisiae for the analysis of intra-population diversity of gene expression
Nature Protocols (2007) 2/9, 2203-2211.


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