Understanding the origins of multicellularity and the organization of complex life is a critical endeavor in biology. Past studies on the transition from single cells to multicellular entities mostly focused on volvocine green algae and early radiating animal taxa as experimental systems. While multicellular bacteria exist, their organization appears comparatively simple, and multicellularity seems to occur only as an adaptation to changing environmental conditions or as a single step in a complex life cycle.


A group of delta-Proteobacteria termed multicellular magnetotactic bacteria (MMB) constitutes the only known exception to this view. MMB are mono-species consortia typically 3-15 μm in size. They are comprised of 10-60 cells arranged in symmetry around a central acellular compartment. Each cell is multiply flagellated and contains magnetic crystals, called magnetosomes, which are used to guide the consortia along the geomagnetic field lines. The life cycle of MMB has no known unicellular stage. Division occurs by separation of a MMB into two apparently identical daughter consortia, while disaggregated cells rapidly lose viability. These characteristics render MMB the only identified bacteria with an obligate multicellular lifestyle and make them a prime subject for evolutionary biology research, the cellular and molecular organization of multicellular entities, and the extent of division of metabolic labor and cellular differentiation. We recently developed a new correlative microscopy workflow to study MMB and other uncultured cells.

Our research activities focus on microbial ecophysiology: the study of the physiology of microorganisms with respect to their habitat. We are interested in how the activity of the “uncultured majority” – the large number of microbes that evades cultivation under laboratory conditions – impacts humans and the environment on a micron to global scale. We are convinced that only by gaining an understanding of microbes directly in their habitats researchers will be able to elucidate the mechanisms of microbial interactions with the biotic and abiotic world. To accomplish these goals, we apply an integrative approach that bridges the two extremes of the microbial scale bar: the individual cell and the whole community. Broadly, the questions we addresses are:

Video: MMB reacting to a magnetic field.

Multicellular magnetotactic bacteria: a window into the early evolution of advanced life


We also develop novel correlative microscopy approaches that allow us to link the metabolic state of cells (active or inactive) with their identity (FISH), morphology (FEM/SEM), elemental/mineralogical composition (EDS/XRD), biochemistry (Raman), and isotopic make-up (nanoSIMS). We have recently published a first benchmarking study on linking active cells and mineralogy in intact sediment cores and developed a noveSIP-FISH-SEM-Raman-NanoSIMS workflow that is applicable to most sample types.


We recently were awarded a NIH MIRA to develop novel activity-targeted approaches to catapult the human gut microbiome field into an era of single cell ecophysiology investigations. In collaboration with the Metrodora Institute, we will analyze mucosal samples via a combination of SIP, SAP, Raman microspectroscopy, and correlative microscopy approaches, which together will reveal the identity, activity, and function of gut microorganisms at individual cell resolution under close-to in situ in vivo conditions. 

​​​Investigated by:  Stavros Trimmer


Our research is funded by the Moore–Simons Project on the

Origin of the Eukaryotic Cell.   MSU press release

Aerobic methane generation by a single genetically transferrable enzyme

In collaboration with the labs of Andreas Teske (Univ. of North Carolina, Chapel Hill), Brett Baker (Univ. of Texas at Austin), Samantha Joye (U Georgia), Virginia Edgcomb (WHOI), and Karthik Anantharaman (U Wisconsin) we study the genomics and ecophysiology of uncultured bacteria and archaea in cold and hydrothermal sediments in the Guaymas and Pescadero deep-sea basins in the Gulfs of California and Baja, respectively. Specifically, we seek to determine​ the identities, in situ activities, and niche-determining factors of cells involved in the degradation of high molecular weight carbon (HMW) compounds of photosynthetic origin, detrital protein and lipids, and HMW hydrocarbons, as well as deep-sea methanogenic lineages. We also seek to determine how pressure, temperature, and other physicochemical parameters affect microbial in situ activity. Techniques used in this line of research include lab mesocosms that replicate in situ conditions (e.g., temperature, pressure), BONCAT-FACS, SIP-Raman, and metatranscriptomics.


Investigated by: Andrew Montgomery and Sylvia Nupp.

Some of the currently most pressing questions are: do individual cells within MMB consortia exhibit cell differentiation and division of labor? Are the consortia clonal and, if not, what are the evolutionary consequences? Which genetic factors do MMB share with other multicellular microbes and which ones set them apart from their unicellular relatives? What is the diversity and ecophysiology of MMB? What are the factors controlling their ecology and the fine interplay of aero-, chemo-, magneto-, and phototaxis?


Investigated by: George Schaible​​

​​Microbial activities in cold and hydrothermal deep-sea sediments

Our work on Guaymas and Pescadero basin microbiology and biogeochemistry is supported by the Systems and Synthetic Biology, Biological Oceanography, and Chemical Oceanography programs of the NSF. Previous research on microbes in coastal sediments was supported by the Gordon and Betty Moore Foundation. 

Developing ​novel Next-generation physiology and correlative microscopy approaches

The term “methane paradox” refers to the oversaturation of methane in many oxic marine and freshwater water columns for which classical archaeal methanogenesis has been ruled out as a source. Our collaborators Tim McDermott and Qian Wang (both MSU) have recently discovered a novel pathway for methane generation from methylamine that is co-responsible for the “methane paradox” in Yellowstone Lake. They have recently published their discovery in which our lab played a small role. Their research demonstrates that a single gene from a freshwater bacterial isolate (Acidovorax sp.) is responsible for generating methane from methylamine under aerobic conditions. If cloned into E. coli, this gene transforms E. coli into a methane-generating microbe! We are now working with Qian and Tim to better understand the environmental impact of this novel methane-generating reaction, its biochemistry, its ecology, as well as the ecophysiology of Acidovorax in Yellowstone Lake.​


​​Investigated by:  Will Christian and Zack Jay​​, in close collaboration with Tim McDermott.


This work is supported by the Synthetic Biology program and the joint JGI-EMSL FICUS program of JGI and EMSL (as well as a NASA Exobiology award to Tim McDermott).


Read MSU press release on Qian's and Tim's initial discovery

Research on MMB is funded by the NASAExobiology and FINESST programs.

Video: Five Sisters hot springs group.





Our hot spring research is supported by a FICUS project with the JGI and EMSL, a CSP project by the JGI, an NSF EPSCoR project, the NASA Exobiology program, and the Thermal Biology Institute at MSU. Research is performed in collaboration with Emiley Eloe-Fadrosh, Bob Bowers, and Tanja Woyke (GI), as well as Tim McDermott, Bill Inskeep, Robin Gerlach, and Brent Peyton at MSU.

Best of" video, research cruise AT42-05 that sampled Guaymas basin sediments. Credit: WHOI and R. Hatzenpichler.

NASA Exobiology grant to McDermott

The origin of eukaryotes represents an unresolved puzzle in the evolutionary history of life. Several lines of evidence suggest that eukaryotes evolved from an endosymbiotic event between an archaeal host cell and an alpha-proteobacterium, which later became the mitochondrion. The recently discovered Asgard superphylum comprises the closest extant archaeal relatives of eukaryotes known so far. Our collaborators Prof. Thijs Ettema (Wageningen U), whose lab discovered Asgard archaea, and Prof. Brett Baker ((Univ. of Texas at Austin) have recently completed an examination of the physiologies of all currently described Asgard phyla. Together with their labs, and the lab of Prof. Mark Ellisman we recently started a project aimed at determining the ecophysiology of Asgard archaea and studying their symbiotic interactions that possibly led to the formation of the first eukaryotic cell, as well as their cellular ultrastructure. The recalcitrance to cultivation of Asgard archaea makes them prime targets for the Next Generation Physiology approaches pioneered by our lab. While the Ettema and Baker labs study the genomics and evolutionary history of Asgard archaea, our lab focuses on experimentally testing hypotheses on their growth substrates

Our lab was recently awarded a NIH MIRA award to develop new single cell resolved tools and correlative microscopy approaches for human gut microbiome research. In the past, our work was funded by the Gordon and Betty Moore Foundation and NASA. Our work on developing a new Raman-activated cell sorter is performed in collaboration with Erik Grumstrup and Stephan Warnat (both MSU) and is funded by the NSF. The acquisition of a Confocal Raman microscope,  spearheaded by Roland, was funded by the NSF MRI program and the M.J. Murdock Charitable Trust. Read a recent MSU news article on our new NIH-funded project on the human gut microbiome.

(1) who is doing what (linking phylogenetic identity and physiological function), (2) what are the abiotic and biotic factors controlling microbial in situ activity, (3) how does this activity affect the environment and ultimately humans, (4) what are the limits to metabolism in terms of energy, space, and time, and (5) how can we discover novel structures and functions within uncultured microbial lineages?

​Our approach to these problems is inherently multi-disciplinary and multi-scaled. In order to address previously unrecognized physiologies and cellular interactions of uncultured microbes, we employ a unique combination of metagenomics (as hypotheses generator), high-through-put metabolic screening via substrate analog probing (to identify geochemical and biotic parameters driving ecology), and single cell resolved stable isotope probing via Raman microspectroscopy or nano-scale secondary ion mass spectrometry (to identify specific growth-sustaining substrates). These culture-indepedent approaches are complemented by mesocosm experiments run under close to in situ conditions and targeted cultivation efforts. Because, together, these approaches target the whole microbiome as well as the individual cell we typically do not depend on samples enriched in a target population, as is often necessitated in ecological studies. Our main study sites are sediments from a variety of geothermal, deep-sea, and coastal habitats.

Biogeochemical functionin situ activity, and cultivation of hot spring archaea

If you are interested in learning more about Next-generation physiology approaches, please read our recent review. Next-generation physiology methods are either targeted at intrinsic characteristics of the cell (label-free methods) or employ substrate analog probing or stable isotope probing to study the in situ phenotype of cells. For a protocol on how to perform BONCAT-experiments see our book chapter. For talking about or teaching about BONCAT, free to use our slides.

We study the ecological niches, biogeochemical roles, in situ activities, and biotechnological potential of lineages of (hyper)thermophilic uncultured archaea in geothermal features of Yellowstone National park. We currently focus our efforts on Korarchaeota, Verstraetearchaeota, and Thaumarchaeota and are interested in expanding our view towards novel groups, e.g. a newly discovered archaeal class we named Culexarchaeia. For this, we recently performed a microbiological and geochemical survey of >100 features in five regions of Yellowstone National Park (YNP, see map to the right). Amongst other excited results, we have identified YNP to be a yet unrecognized hot spot for anaerobic methane cycling. ​We achieve our goal of linking new archaeal taxonomies with in situ function by a combination of metagenome sequencing of environmental DNA and testing genome-derived hypotheses by single cell targeted physiology, including stable isotope probing and bioorthogonal labeling. The latter two approaches distinguish our lab from many other labs, who do not put their genomic hypotheses to an experimental test. We have also have important progress in bringing previously uncultured lineages of archaea into culture.


Investigated by: Zack Jay, Anthony Kohtz, Mackenzie Lynes, Sylvia Nupp, and Paige Schlegel.

If the physiology of uncultured cells is to be determined, approaches that target the single cell level are essential in order to link the identity of a cell to its specific function. Ideally, these approaches are not destructive to the cell so that it can be analyzed using complementary downstream applications, for example targeted cultivation or genome sequencing. Our lab has recently introduced the term Next-generation physiology approaches to refer to such techniques. One such technique, developed by our lab, is bioorthogonal non-canonical amino acid tagging (BONCAT), which allows protein-synthesizing cells in complex microbiomes to be visualized. When used in conjunction with rRNA-targeted fluorescence in situ hybridization (FISH), BONCAT allows the identity of a cell and its in situ activity to be linked. BONCAT is intrinsically high throughput and, when combined with cell-sorting devices enables cells to be separated from samples based on their anabolic activity and to study the response of microbes to substrate amendment. In contrast to isotope labeling approaches, which require highly specialized instruments, BONCAT-FISH and BONCAT-FACS use standard microscopes and flow cytometers that are readily available to microbiology labs. While we also target other classes of biomolecules (DNA, lipids, peptidoglycan) in our work and are developing new approaches to target cellular in situ activity on single cell level, proteins are currently our main target.


In addition to bioorthogonal labeling, we use stable isotope probing in combination with single cell visualization instruments to study substrate uptake and in situ activity. Specifically, we use SIP-FISH-Raman (via a Horiba Confocal Raman microspectroscope that was brought to MSU by Roland in 2019) to study the biochemistry and in situ biogeochemical function of uncultured cells. In collaboration with other researchers at MSU, we also are developing new Raman-activated cell sorting technology. In addition, we collaborate with the Environmental Molecular Sciences Laboratory to use their nano-scale secondary ion mass spectrometry (nanoSIMS) instrument.