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-throughput 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 tools 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). The analysis of the heterogeneity of cells in clonal cultures is another focus of our research. Here, specific cell characteristics such as growth, viability, productivity or plasmid stability are some of our research targets.

The working group 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 of complex microbial communities  can be evaluated using the following tools:

Cytometric Histogram Image Comparison (flowCHIC: doi: 10.1002/cyto.a.22286)
Cytometric Barcoding (flowCyBar: doi:10.1038/nprot.2012.149)
Automated Gate Setting (flowEMMi: doi.org/10.1016/j.csbj.2022.11.033)

Current Research

Deutsche Forschungsgemeinschaft (DFG)
Aktenzeichen: GZ: MU 1089/10-1, AOBJ: 687645
Projektnummer: 503905203
Schwerpunktprogramms (SPP) "Emergente Funktionen der bakteriellen Multizellularität"
Analyse der lokalen Struktur und Funktion von bakteriellen Kolonien und Biofilmen auf Einzelzellebene mittels Durchflusszytometrie, Zellsortierung, Multi-omics und Datenwissenschaft -
Total: 556.550 €

Gordon and Betty Moore Foundation
Grant Number: GBMF9730
Resolving archaeal contributions to the first eukaryotic common ancestor: Developing new tools for accessing the genomes of uncultivated archaea.
In cooperation with the University of California, Santa Barbara Earth Research Institute
Total: 23 K€

EU- H2020- Horizon 2020 Societal Challenge 2
Aktenzeichen: Proposal 101000733 – PROMICON
PROMICON - FNR-12-2020 - Industrial microbiomes – learning from nature
Harnessing the power of nature through productive microbial consortia in biotechnology – Measure, Model & Master (PROMICON)
Total: 200 k€ UFZ, AG Flow Cytometry

Chinese Scholarship Council (CSC)
China, Ministery of Education
‘Construction of functionally active artificial communities based on individual cell analyses and ecological theory’
Total: Scholarship

Selected Publications

Jurburg SD, Eisenhauer N, Buscot F, Chatzinotas A, Chaudhari NM, Heintz-Buschart A, Kallies R, Küsel K, Litchman E, Macdonald CA, Müller S, Reuben RC, da Rocha UN, Panagiotou G, Rillig MC, Singh BK.
Potential of microbiome-based solutions for agrifood systems
Nature Food (2022) DOI - 10.1038/s43016-022-00576-x

Li S, Abdulkadir N, Schattenberg F, Rocha UN, Grimm V, Müller S, Liu Z
Stabilising microbial communities by looped mass transfer
Proceedings of the National Academy of Sciences (PNAS) (2022) 119/17, e2117814119

Cohen Y, Pasternak Z, Müller S, Hübschmann T, Schattenberg F, Sivakala KK, Abed-Rabbo A,
Chatzinotas A & Jurkevitch E
Community and single cell analyses reveal complex predatory interactions between bacteria in high-diversity systems.
Nature Communications (2021) 12, 5481.

Vučič V, Süring C, Harms H, Müller S, Günther S.
A framework for P-cycle assessment in wastewater treatment plants.
Science of the Total Environment (2021) 760C, 143392.

Cichocki N, Hübschmann T, Schattenberg F, Kerckhof FM, Overmann J, Müller S.
Bacterial mock communities as standards for reproducible cytometric microbiome analysis.
Nature Protocols (2020) 15, 2788-2812. DOI: 10.1038/s41596-020-0362-0

Haange SB, Jehmlich N, Krügel U, Hintschich C, Wehrmann D, Hankir M, Seyfried F, Froment J, Hübschmann T, Müller S, Wissenbach DK, Kang K, Buettner C, Panagiotou G, Noll M, Rolle-Kampczyk U, Fenske W, von Bergen M.
Gastric bypass surgery alters the community structure and functional composition of the intestinal microbiota independently of weight loss.
Microbiomes (2020) 8/13

Krause JL, Schaepe SS, Fritz-Wallace K, Engelmann B, Rolle-Kampczyk U, Kleinsteuber S, Schattenberg F, Liu Z, Mueller S, Jehmlich N,Von Bergen M, and Herberth G.
Following the community development of SIHUMIx – a new intestinal in vitro model for bioreactor use.
Gut Microbes (2020) doi.org/10.1080/19490976.2019.1702431

Liu Z, Müller S.
Bacterial community diversity dynamics highlight degrees of nestedness and turnover patterns.
Cytometry Part A (2020) doi.org/10.1002/cyto.a.23965

Lambrecht J, Cichocki N, Schattenberg F, Kleinsteuber S, Harms H, Müller S, Sträuber, H
Key sub-community dynamics of medium-cain carboxylate production
Microbial Cell Factory (2019) 18:92.

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 (2019), 21/1, 164-181.

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 diagnostics.
Molecular Aspects of Medicine (2018), 59, 123-134

Günther 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

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

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.

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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