BTI members connect with colleagues in Japan

BTI members connect with colleagues in Japan

BTI members connect with colleagues in Japan

BioTechnology Institute members travel to the University of Tokyo to strengthen research ties.

By Lance Janssen

Despite hours-long flights and an ocean of separation, researchers from the BioTechnology Institute (BTI) and the University of Tokyo have close connections. This past November, eight BTI faculty members traveled to Japan for a shared research symposium as a continued piece of an academic exchange program launched between the two institutions in 2017. With common research focus areas in areas like ​​microbial engineering, synthetic biology, protein design and environmental engineering, as well as opportunities to build connections and train students, the initiative aims to offer opportunities that will advance research and educational efforts for both BTI and the University of Tokyo.

“Our hope is that we can build collaborations with researchers that have shared interest areas and complementary scientific skills and expertise,” says Jeff Gralnick, a professor in the Department of Plant and Microbial Biology and a BTI member. “By establishing a student and postdoc exchange program, we also hope to provide important learning experiences for our trainees.”

Gralnick attended this year’s symposium along with Alptekin Aksan from the College of Science and Engineering, Christine Salomon from the College of Pharmacy and Medical School, as well as Michael Freeman, Kate Adamala, Michael Travisano and Claudia Schmidt-Dannert from the College of Biological Sciences. The symposium not only offered researchers the chance to share some of their research endeavors in Minnesota, but also build closer connections with their Tokyo counterparts. 

“The University of Tokyo is the premier research institution in Japan – with excellent research groups that conduct complementary research to BTI faculty,” says Schmidt-Dannert, head of BTI and a professor in the Department of Biochemistry, Molecular Biology and Biophysics. “Through this symposium we were able to learn first-hand about specific research conducted at the University of Tokyo through lectures, visits to labs and meetings with students, researchers and faculty – both in a formal but also more informal setting – and get insights into the academic environment and culture in Japan.”

Over the course of their visit, the BTI team took part in the symposium, as well as tours to the Mt. Fuji area, a formal banquet with colleagues and a visit to the National Institute of Genetics. These experiences offered researchers the chance to not only learn about research and visit a new city, but also future research opportunities for years to come.

“I think all of us identified areas of overlap for research collaboration,” says Schmidt-Dannert. “Some concrete connections have already been made that will result in material exchange and hosting of students and postdocs. We will use all of the knowledge and experience gathered to identify and apply for joint funding opportunities and develop a program that will allow for an exchange of graduate students and potentially postdocs between BTI and University of Tokyo labs.” 

Symposium presentations

Structural and metabolic insights in RiPP peptide backbone α-N- methylation.
Michael Freeman (University of Minnesota)

Natural product discovery for biocontrol and infectious disease treatment.
Christine Salomon (University of Minnesota)

Molecular Plant-Microbe interactions along the parasitic-mutualistic continuum.
Ke Hirumai (University of Tokyo)

Life but not alive: bioengineering with synthetic cells.
Kate Adamala (University of Minnesota)

Leveraging biological self-organization for the design of functional materials.
Claudia Schmidt-Dannert (University of Minnesota)

Molecular mechanisms of morphological development in the rare actinomycete Actinoplanes missouriensis.
Yasuo Ohnishi (University of Tokyo)

Extracellular electron transfer in Bacteria.
Jeffrey Gralnick (University of Minnesota)

Bioremediation of nitrate pollution in agricultural subsurface drainage.
Satoshi Ishii (University of Minnesota)

Plasmid business: effects to host cell physiology and fate in nature.
Hideaki Nojiri (University of Tokyo)

Active biomaterials for biotechnology applications.
Alptekin Aksan AKSAN (University of Minnesota)

Exploring microbial solutions using Experimental Evolution.
Michael Travisano (University of Minnesota)

Bioinformatics for revealing rules behind microbial genome evolution.
Wataru Iwasaki (University of Tokyo)

Enzyme advances promise to boost the bioeconomy

Enzyme advances promise to boost the bioeconomy

Enzyme advances promise to boost the bioeconomy

Enzyme technology symposium brings together researchers from North America and Japan working on cutting-edge applications.

By Stephanie Xenos

Around 85 researchers and industry partners involved in developing new enzyme-based applications recently came together at the University of Minnesota for the 1st North America-Japan Enzyme Technology Symposium. The symposium, organized by the BioTechnology Institute and Amano Enzyme Japan, focused on enzyme technology relating to biocatalysis and food, two key areas of the growing bioeconomy. 

“This symposium provided opportunities for new collaborations and learning about new enzyme applications that are particularly relevant for advancing the bioeconomy in Minnesota given the abundant agricultural and forest resources in our state,” says Claudia Schmidt-Dannert, director of the BioTechnology Institute.

Speakers covered a range of topics including modifications in the rate at which plants absorb light, in wood xylan to make polymers for food packaging, and in polyunsaturated fatty acids to make therapeutics.

“Enzyme applications make our lives better and our environment cleaner but most people are unaware of their importance since they work for us out of sight,” says Romas Kazlauskas, a professor in Biochemistry, Molecular Biology and Biophysics, and one of the organizers of the symposium. “Enzymes make our laundry detergents more effective, are used to make the COVID-19 drug Paxlovid, and improve the texture and taste of our foods. This symposium provided examples of current and future applications of enzymes.”

The symposium provided students and postdocs to engage with experts from industry and academia, and learn about the breadth of enzyme applications.

A selection of symposium talks are available to view.

Building New Metabolic Pathways

Building New Metabolic Pathways

By Kevin Coss

Microbes are nothing if not industrious. The metabolic pathways (linked series of chemical reactions) in these tiny organisms lead them to crank out a wide variety of molecules for all sorts of purposes — and that’s what has Mike Freeman’s attention.

“Some of these pathways are for chemical communication, some are for warfare, and others are completely unknown to us,” says Freeman, Ph.D., member of the University of Minnesota BioTechnology Institute and assistant professor of biochemistry, molecular biology, and biophysics. “A large part of what our lab does is looking at those genes and those pathways in unique organisms and studying them for the purpose of both basic science and biotechnology.”

Freeman’s research involves understanding how each piece of a biological system works and then combining and mixing those parts to “recircuit” pathways. This field, synthetic biology, aims to redirect microbes’ natural industriousness to produce a different, more desirable product. The intended purpose can span a wide range of applications, from producing compounds that help address bacteria’s growing resistance to antibiotics to developing molecules for use in the fragrance industry.

“You could use a microbe to do something it doesn’t already do in nature, for example, or engineer it to do it much better,” Freeman says. “We’re trying to put things together in unique ways to do what humans want, not what nature wants.”

Understanding the full scope of how a given pathway works, what it produces, and what larger purpose it serves requires a wealth of expertise. Fortunately, Freeman is part of the Synthetic Biology Research Cluster, which brings together faculty, postdoctoral fellows, staff, and students who study in the field to intermingle and learn from one another. This arrangement helps to spark collaborations that inspire new lines of research and enables the group to apply for larger grants with multiple principal investigators.

Freeman’s current research focus is on modifications that give molecules called peptides (smaller versions of proteins, with fewer pieces acting as “links” in their chain) more desirable properties. Peptide-based medications, such as the insulin used to treat diabetes, generally can’t be taken orally because stomach acids destroy the active compounds before they can provide any benefit. Modifying these peptides to remain stable through the digestive tract would open the possibility for peptide-based drugs to be taken as a pill — an option that makes it easier and more comfortable for patients to adhere to their medication schedule.

As another example, Freeman and his team are studying anti-cancer compounds derived from a specific type of fungus. Two promising varieties of peptides had previously been isolated from it, but the team went further in depth to study and isolate other “flavors” of these peptides with unique and useful characteristics. By optimizing the growing conditions in the lab for the fungi’s mycelia — the long, stringlike filaments that spread through the soil — they have been able to isolate a number of compounds from this fungus.

Apart from the medical field, a stronger understanding of synthetic biology could also help solve problems in manufacturing, agriculture, and other industries. While these solutions are appealing, what inspires Freeman the most about his research is the basic science — specifically, how much of it remains undiscovered.

In many other areas of science, researchers build upon a strong foundation of existing knowledge. Synthetic biology is different. It’s only recently that advances in genomic technology made it possible to study the workings and purposes of genes, proteins, and pathways at this level of detail.

“In some cases, the enzymes that we find, the pathways, the molecules have never been seen before in science,” he says. “Being able to explore these unknowns and add to the general scientific knowledge for humanity is what’s really satisfying to me.”

Tapping the Talents of Enzymes

Tapping the Talents of Enzymes

BTI researchers are working to discover, understand, and improve our ability to enlist the help of molecules that catalyze life.

by Mary Hoff

Enzymes are the movers and shakers of the biomolecular world. A class of proteins found in every cell of every living thing, they bring together molecules that would otherwise be reluctant to interact so they can combine, exchange parts, or otherwise alter each other.

In nature, enzymes facilitate thousands of processes from photosynthesis to decomposition. Enzymes speed up chemical reactions thousands of times faster than the reactions would occur on their own. Over the millennia, humans have found ways apply this superpower to accomplish a variety of useful goals from making beer and cheese, to making our laundry whiter and brighter, to cranking out millions of copies of a sample of DNA to solve crimes or find long-lost relatives.

“And that’s just the beginning,” says Romas Kazlauskas, professor in the department of Biochemistry, Molecular Biology, and Biophysics. “Enzymes can also learn how to do different things. We’re trying to figure out which parts are important and why they’re important, then design something different to do a reaction that doesn’t occur naturally.” By identifying enzymes, improving understanding of how they work, and applying them to new tasks, Kazlauskas and BTI colleagues are taking advantage of the billions of years of evolution that produced these molecules to make medicines, degrade pollutants, speed industrial processes, and more.


Trash to Treasure Kazlauskas is working with an enzyme found in nature that degrades PET plastic. First synthesized in the 1940s, PET (a form of polyethylene) is widely used for beverage and food containers with some 70 million tons generated every year—and much of that ending up in landfills and the ocean. Current efforts to recycle the material can only produce lower-quality plastics.

“One idea is to break down to component parts and resynthesize fresh plastic that would be just as good as what you started with,” he says.

Sound like a job for an enzyme? Kazlauskas thought so, too. But the likelihood of finding a suitable one in nature was slim because PET didn’t exist for most of evolutionary history. Nevertheless, in a compost heap in Japan, researchers recently found an enzyme that bacteria use to break down the waxy part of plants that could also break down PET.

Kazlauskas, along with graduate student Colin Pierce and colleagues, is working on modifying that enzyme known as cutinase, to improve its ability to degrade PET. The goal, ultimately, is to be able to develop a commercially viable way to turn old PET into new plastics without experiencing the loss of quality. This would not only reduce the load of plastic waste, it would also reduce pressure to produce more plastic, often from fossil fuels.

Kazlauskas sees huge opportunities beyond PET for efforts to extend nature’s ability to degrade compounds. “There are a lot of cases where we start making stuff and putting it out in nature, and people say it doesn’t degrade,” he says. “We’re finding bugs that can degrade these forever chemicals.” he says. By advancing the ability to modify such natural enzymes to make them do the job even better, the hope is to avoid the buildup of undesirable, manufactured compounds in the environment and reduce the need to make more from raw materials.


Life on the Edge

Turning somersaults in a sulfurous hot spring or clinging tenaciously to life on a glacier, the organisms studied by McKnight Presidential Fellow Trinity Hamilton, associate professor in the department of Plant and Microbial Biology, are the stars in microscopic world’s version of “Survivor.” Having evolved within living things, most enzymes work best under fairly mild conditions with respect to things like temperature and acidity. But not all. In the hot springs of Yellowstone National Park, Hamilton is studying how microbes—and the enzymes they use to carry out the activities of daily life—can survive regular temperature fluctuations of 40 degrees Celsius (104 degrees Fahrenheit) or more. And, on the other end of the spectrum, she’s also looking at how other microorganisms that live on ice maintain their function at low temperatures in the absence of liquid water.

Hamilton studies, among other things, enzymes that facilitate photosynthesis and function well up to 72 degrees Celsius, and then suddenly quit. “We have no idea why,” she says. “It’s really hard to perform autopsies on microbes.”

The ability of bacterial enzymes to function at various temperatures is behind the process that makes it possible to sequence DNA using what is called the polymerase chain reaction (PCR) technique. The enzyme used for this was isolated from bacteria in a hot spring in Yellowstone National Park. A better understanding of how bacteria keep these proteins active under extreme conditions could open the door to advancing our ability to solve other human challenges like preserving food or thriving in the face of climate change.

Molecular Assembly Line 

For Michael Smanski, a McKnight land grant professor in the department of Biochemistry, Molecular Biology, and Biophysics, the focus is on bringing together enzymes from different sources to create an efficient work team that can produce a specific molecule.

Most recently he’s been focusing on serofendic acid, a molecule found in the blood of fetal calves. In the early 2000s, researchers in Japan discovered that serofendic acid could prevent the untimely death of neurons and potentially serve as a therapy for minimizing damage from Parkinson’s disease, strokes, and other neurological trauma. The problem? It occurs in such small quantities that it would take 1,000 calves to make a minute 3 milligrams of active substance—providing dismal prospects for practical use.

Biosynthesis and enzymes to the rescue. Using databases describing enzymes from different organisms and the type of work each does, Smanski and colleagues designed a molecular assembly line that could make serofendic acid from readily available feedstock chemicals. Then they introduced the corresponding genes into a bacterium, enabling it to make the desired product.

As any industrial engineer would know, populating an assembly line with ready workers is only part of the solution, however. For efficiency’s sake, it’s also important to have the right capacity at every step of an assembly process to ensure that partially made products don’t pile up, or a slow step doesn’t drag down everything else. To optimize production of serofendic acid, Smanski has been tweaking the activity levels of the various enzymes relative to each other.

Even as he’s working on a strategy to improve outcomes for individuals with brain disorders, Smanski is also discovering principles that can be applied more broadly to optimizing artificial biosynthetic processes.

Optimizing a process means testing multiple levels of expression for the specific gene that’s coding for each enzyme along the way. If the assembly line consists of 15 enzymes, and researchers want to test five levels of expression for each, that would require 5 15 power—more than 30 billion—individual trials. Using combinatorial mathematics, Smanski is devising a strategy for selecting from those millions of possibilities, a mere 100 or so that are most likely to succeed, making the optimization process far more manageable.

“As improvements in the technical aspects of genetic engineering make it easier to rewrite the genetic blueprints of living organisms, learning how to efficiently sift through all of the possibilities of what-to-write is becoming more important,” Smanski says. “We think that our work at the interface of combinatorial mathematics and genetic engineering will benefit any application that requires more than one or a few genes working together.”


Self-Assembling Scaffold

Bringing multiple enzymes together in an assembly line is far more easily said than done. The molecules involved in sequential steps must be physically located close enough to each other to be able to pass a product-in-the-making down the line. They also must be positioned correctly at their stations so they can accomplish their task.

Distinguished McKnight University Professor Claudia Schmidt-Dannert is on it. Rather than identifying enzymes to string together to accomplish a molecule-making task, she is working on the assembly line itself.

Her goal is to not only design a stable assembly line of enzymes able to make a useful product but to genetically modify a microorganism—say, the bacterium E. coli—so that it can produce it on its own. Such a self-assembling scaffold, she believes, could dramatically improve the function of molecular assembly lines, reducing the cost of producing pharmaceuticals and other useful products.

“If we stabilize enzymes, we can make reactions more efficient,” she says.

Schmidt-Dannert and colleagues recently received a patent for a self-assembling, modular scaffold that co-locates enzymes in a way that enhances their ability to efficiently produce desired molecules. Her current focus is on developing scaffolds as materials that can correctly self-assemble into 3-dimensional architectures to organize and support enzyme functions. This would allow the manufacture of a broad range of chemicals including pharmaceutically active molecules—a process that can be extremely difficult using conventional chemical synthesis methods. 

She’s also applying her strategy to making molecular assembly lines more economical by including enzymes that recycle required co-factors, which are molecules or metals that assist enzymes in assembling a molecular product.

“You need to recycle the [co-factors]. Otherwise, the process is too expensive,” she says. “A scaffold helps make that possible.”


About BTI

About BTI

About BTI

The BioTechnology Institute’s (BTI) mission is to advance cross-disciplinary research and innovation at the forefront of biotechnology. BTI supports biotechnology workforce development, facilitates industry interactions, and provides biomanufacturing services through its BioResource Center (BRC). The Institute is the central University of Minnesota vehicle for coordinated research in the biological, chemical, and engineering aspects of biotechnology. 

Innovative Research

BTI faculty conduct research over a broad spectrum of disciplines including microbial physiology, metabolic pathway engineering, genetics and cell biology, functional genomics, animal cell culture, biodegradation of hazardous materials, molecular evolution, biological diversity, green chemistry, natural product synthesis, protein engineering, and the development of biofuels and biopolymers from renewable resources.

Professional Training

Since 1990, the Institute has been the recipient of the prestigious NIH Training Grant in Biotechnology. This grant has provided financial support to graduate students completing degrees in biochemistry, microbiology, chemical engineering, chemistry, genetics, computer science, biomedical engineering, plant sciences, mathematics, health informatics, and electrical engineering. Many of these students have gone on to complete a PhD. 

Reflecting its cross-disciplinary nature, the Institute offers a Master of Science degree in Microbial Engineering. This program is favorably regarded by industry as a source of highly trained individuals familiar with both the biological sciences and engineering.

A Resource for Industry

In addition to the faculty laboratories, the Institute has established the Biotechnology Resource Center (BRC); a process scale pilot plant unique in the state and accessible to industrial and academic scientists for collaborative and contract research. The BioTechnology Institute also coordinates an active industrial outreach program that sponsors short courses and mini-symposia.

Biotechnology Resource Center

BTI publications: March – mid April 2024

BTI publications: March – mid April 2024

Collins, J., & Hackel, B. J. (2024). Sequence-activity mapping via depletion reveals striking mutational tolerance and elucidates functional motifs in Tur1a antimicrobial peptide. Protein Eng Des Sel, 37.

Dogterom, M., Kamat, N. P., Jewett, M. C., & Adamala, K. P. (2024). Progress in Engineering Synthetic Cells and Cell-Free Systems. ACS Synth Biol, 13(3), 695-696.

Du, Z., & Behrens, S. F. (2024). Effect of target gene sequence evenness and dominance on real-time PCR quantification of artificial sulfate-reducing microbial communities. PLoS One, 19(3), e0299930.

Hajiaghabozorgi, M., Fischbach, M., Albrecht, M., Wang, W., & Myers, C. L. (2024). BridGE: a pathway-based analysis tool for detecting genetic interactions from GWAS. Nat Protoc.

Harcombe, W. R. (2024). Taking mechanomicrobiology from local to global. Biophys J.

Hu, X., Zhou, Y., Liu, R., Wang, J., Guo, L., Huang, X., . . . Zhou, S. (2024). Protein disulfide isomerase 1 is required for RodA assembling-based conidial hydrophobicity of. Appl Environ Microbiol, e0126023.

Hying, Z. T., Miller, T. J., Loh, C. Y., & Bazurto, J. V. (2024). Glycine betaine metabolism is enabled in. Appl Environ Microbiol, e0209023.

La Reau, A. J., Strom, N. B., Filvaroff, E., Mavrommatis, K., Ward, T. L., & Knights, D. (2024). Author Correction: Shallow shotgun sequencing reduces technical variation in microbiome analysis. Sci Rep, 14(1), 6116.

Levrier, A., Bowden, S., Nash, B., Lindner, A., & Noireaux, V. (2024a). Cell-Free Synthesis and Quantitation of Bacteriophages. Methods Mol Biol, 2760, 447-461.

Levrier, A., Karpathakis, I., Nash, B., Bowden, S. D., Lindner, A. B., & Noireaux, V. (2024a). PHEIGES: all-cell-free phage synthesis and selection from engineered genomes. Nat Commun, 15(1), 2223.

Lewis, N. M., Kisgeropoulos, E. C., Lubner, C. E., & Fixen, K. R. (2024). Characterization of ferredoxins involved in electron transfer pathways for nitrogen fixation implicates differences in electronic structure in tuning 2[4Fe4S] Fd activity. J Inorg Biochem, 254, 112521.

Litsios, A., Grys, B. T., Kraus, O. Z., Friesen, H., Ross, C., Masinas, M. P. D., . . . Andrews, B. J. (2024). Proteome-scale movements and compartment connectivity during the eukaryotic cell cycle. Cell, 187(6), 1490-1507.e1421.

Liu, X., Igarashi, D., Hillmer, R. A., Stoddard, T., Lu, Y., Tsuda, K., . . . Katagiri, F. (2024). Decomposition of dynamic transcriptomic responses during effector-triggered immunity reveals conserved responses in two distinct plant cell populations. Plant Commun, 100882.

Longhurst, A. D., Wang, K., Suresh, H. G., Ketavarapu, M., Ward, H. N., Jones, I. R., . . . Toczyski, D. P. (2024). The PRC2.1 Subcomplex Opposes G1 Progression through Regulation of CCND1 and CCND2. bioRxiv.

Lu, M., Lin, Y. C., Kuo, H. J., Cai, W., Ye, Q., Zhao, L., & Hu, W. S. (2024). Tuning capsid formation dynamics in recombinant adeno-associated virus producing synthetic cell lines to enhance full particle productivity. Biotechnol J, 19(3), e2400051.

McFarlane, J. A., Garenne, D., Noireaux, V., & Bowden, S. D. (2024a). Cell-free synthesis of the Salmonella specific broad host range bacteriophage, felixO1. J Microbiol Methods, 220, 106920.

Moon, S., Saboe, A., & Smanski, M. J. (2024). Using design of experiments to guide genetic optimization of engineered metabolic pathways. J Ind Microbiol Biotechnol, 51.

Rashidi, A., Ebadi, M., Rehman, T. U., Elhusseini, H., Kazadi, D., Halaweish, H., . . . Staley, C. (2024a). Long- and short-term effects of fecal microbiota transplantation on antibiotic resistance genes: results from a randomized placebo-controlled trial. Gut Microbes, 16(1), 2327442.

Rothschild, L. J., Averesch, N. J. H., Strychalski, E. A., Moser, F., Glass, J. I., Cruz Perez, R., . . . Adamala, K. P. (2024a). Building Synthetic Cells─From the Technology Infrastructure to Cellular Entities. ACS Synth Biol.

Sadowsky, M. J., Matson, M., Mathai, P. P., Pho, M., Staley, C., Evert, C., . . . Khoruts, A. (2024a). Successful Treatment of Recurrent Clostridioides difficile Infection Using a Novel, Drinkable, Oral Formulation of Fecal Microbiota. Dig Dis Sci.

Segawa, T., Takahashi, A., Kokubun, N., & Ishii, S. (2024). Spread of antibiotic resistance genes to Antarctica by migratory birds. Sci Total Environ, 923, 171345.

Shawver, S., Ishii, S., Strickland, M. S., & Badgley, B. (2024). Soil type and moisture content alter soil microbial responses to manure from cattle administered antibiotics. Environ Sci Pollut Res Int.

Sikdar, R., Beauclaire, M. V., Lima, B. P., Herzberg, M. C., & Elias, M. H. (2024). -acyl homoserine lactone signaling modulates bacterial community associated with human dental plaque. bioRxiv.

Simpson, H. J., Andrew, C., Skrede, I., Kauserud, H., & Schilling, J. S. (2024). Global field collection data confirm an affinity of brown rot fungi for coniferous habitats and substrates. New Phytol.

Sompiyachoke, K., & Elias, M. H. (2024). Engineering quorum quenching acylases with improved kinetic and biochemical properties. Protein Sci, 33(4), e4954.

Sreekanta, S., Haaning, A., Dobbels, A., O’Neill, R., Hofstad, A., Virdi, K., . . . Lorenz, A. J. (2024). Variation in shoot architecture traits and their relationship to canopy coverage and light interception in soybean (Glycine max). BMC Plant Biol, 24(1), 194.

Suazo, K. F., Mishra, V., Maity, S., Auger, S. A., Justyna, K., Petre, A., . . . Distefano, M. D. (2024). Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors. bioRxiv.

Sychla, A., Feltman, N. R., Hutchison, W. D., & Smanski, M. J. (2023). Corrigendum: Modeling-informed Engineered Genetic Incompatibility strategies to overcome resistance in the invasive. Front Insect Sci, 3, 1360167.

Wackett, L. P. (2024). Evolutionary obstacles and not C-F bond strength make PFAS persistent. Microb Biotechnol, 17(4), e14463.

Zaret, M., Kinkel, L., Borer, E. T., & Seabloom, E. W. (2024). Plant growth-defense trade-offs are general across interactions with fungal, insect, and mammalian consumers. Ecology, e4290.

BTI publications: February 2024

BTI publications: February 2024

Achberger, A. M., Jones, R., Jamieson, J., Holmes, C. P., Schubotz, F., Meyer, N. R., . . . Sylvan, J. B. (2024). Inactive hydrothermal vent microbial communities are important contributors to deep ocean primary productivity. Nat Microbiol.

Allert, M., Ferretti, P., Johnson, K. E., Heisel, T., Gonia, S., Knights, D., . . . Blekhman, R. (2024). Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother’s milk. bioRxiv.

Bisesi, A. T., Möbius, W., Nadell, C. D., Hansen, E. G., Bowden, S. D., & Harcombe, W. R. (2024a). Bacteriophage specificity is impacted by interactions between bacteria. mSystems, e0117723.

Collins, J., McConnell, A., Schmitz, Z. D., & Hackel, B. J. (2024). Sequence-function mapping of proline-rich antimicrobial peptides. bioRxiv.

Greiss, F., Lardon, N., Schütz, L., Barak, Y., Daube, S. S., Weinhold, E., . . . Bar-Ziv, R. (2024). A genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice. Nat Commun, 15(1), 883.

Janzen, A., Pothula, R., Sychla, A., Feltman, N. R., & Smanski, M. J. (2024). Predicting thresholds for population replacement gene drives. BMC Biol, 22(1), 40.

Li, J., Arnold, W. A., & Hozalski, R. M. (2024). Animal Feedlots and Domestic Wastewater Discharges are Likely Sources of. Environ Sci Technol, 58(6), 2973-2983.

Lin, K., Chang, Y. C., Billmann, M., Ward, H. N., Le, K., Hassan, A. Z., . . . Myers, C. L. (2024). A scalable platform for efficient CRISPR-Cas9 chemical-genetic screens of DNA damage-inducing compounds. Sci Rep, 14(1), 2508.

Lu, M., Lee, Z., & Hu, W. S. (2024). Multi-omics kinetic analysis of recombinant adeno-associated virus production by plasmid transfection of HEK293 cells. Biotechnol Prog, e3428.

Mohamed, M. E., Saqr, A., Staley, C., Onyeaghala, G., Teigen, L., Dorr, C. R., . . . Jacobson, P. A. (2024). Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation. Transplantation.

Oram, M. K., Baxley, R. M., Simon, E. M., Lin, K., Chang, Y. C., Wang, L., . . . Bielinsky, A. K. (2024). RNF4 prevents genomic instability caused by chronic DNA under-replication. DNA Repair (Amst), 135, 103646.

Phan, J., Macwan, S., Gralnick, J. A., & Yee, N. (2024). Extracellular organic disulfide reduction by. Microbiol Spectr, e0408123.

Prakash, A., Rubin, N., Staley, C., Onyeaghala, G., Wen, Y. F., Shaukat, A., . . . Prizment, A. (2024). Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma. Sci Rep, 14(1), 2988.

Sampson, K., Sorenson, C., & Adamala, K. P. (2024). Preparing for the future of precision medicine: synthetic cell drug regulation. Synth Biol (Oxf), 9(1), ysae004.

Tassoulas, L. J., Rankin, J. A., Elias, M. H., & Wackett, L. P. (2024a). Dinickel enzyme evolved to metabolize the pharmaceutical metformin and its implications for wastewater and human microbiomes. Proc Natl Acad Sci U S A, 121(10), e2312652121.

Tassoulas, L. J., & Wackett, L. P. (2024). Insights into the action of the pharmaceutical metformin: Targeted inhibition of the gut microbial enzyme agmatinase. iScience, 27(2), 108900.

Travisano, M. (2024). Managing expectations. Science, 383(6684), 710.

Zhang, L., Wang, P., Wang, X., Zhang, Q., Wang, Y., Liu, Y., . . . Cui, X. (2024). Resource utilization of wastepaper and bentonite: Cu(II) removal in the aqueous environment. J Environ Manage, 353, 120213.

Zmuda, A. J., Kang, X., Wissbroecker, K. B., Freund Saxhaug, K., Costa, K. C., Hegeman, A. D., & Niehaus, T. D. (2024a). A universal metabolite repair enzyme removes a strong inhibitor of the TCA cycle. Nat Commun, 15(1), 846.

BTI publications: January 2024

BTI Publications January 2024

Elias, M. H., Sompiyachoke, K., Fernández, F. M., & Kamerlin, S. C. L. (2024). The ineligibility barrier for international researchers in US academia. EMBO Rep.

Haq, I. U., Christensen, A., & Fixen, K. R. (2024). Evolution of. Appl Environ Microbiol, e0210423.

Heili, J. M., Stokes, K., Gaut, N. J., Deich, C., Sharon, J., Hoog, T., . . . Adamala, K. P. (2024). Controlled exchange of protein and nucleic acid signals from and between synthetic minimal cells. Cell Syst, 15(1), 49-62.e44.

Hozalski, R. M., Zhao, X., Kim, T., & LaPara, T. M. (2024a). On-site filtration of large sample volumes improves the detection of opportunistic pathogens in drinking water distribution systems. Appl Environ Microbiol, e0165823.

Huang, M., Rueda-Garcia, M., Harthorn, A., Hackel, B. J., & Van Deventer, J. A. (2024). Systematic Evaluation of Protein-Small Molecule Hybrids on the Yeast Surface. ACS Chem Biol.

Lee, K. H., Distefano, M. D., & Seelig, B. (2023a). Facile immobilization of pyridoxal 5′-phosphate using p-diazobenzoyl-derivatized Sepharose 4B. Results Chem, 6.

Li, J., Wang, Y., Distefano, M. D., Wagner, C. R., & Pomerantz, W. C. K. (2024). Multivalent Fluorinated Nanorings for On-Cell. Biomacromolecules.

Medina-Chávez, N. O., Torres-Cerda, A., Chacón, J. M., Harcombe, W. R., De la Torre-Zavala, S., & Travisano, M. (2023b). Disentangling a metabolic cross-feeding in a halophilic archaea-bacteria consortium. Front Microbiol, 14, 1276438.

Phan, T., Ye, Q., Stach, C., Lin, Y. C., Cao, H., Bowen, A., . . . Hu, W. S. (2024). Synthetic Cell Lines for Inducible Packaging of Influenza A Virus. ACS Synth Biol.

Robinson, A. O., Lee, J., Cameron, A., Keating, C. D., & Adamala, K. P. (2024). Cell-Free Expressed Membraneless Organelles Inhibit Translation in Synthetic Cells. ACS Biomater Sci Eng.

Schreiber, M., Wonneberger, R., Haaning, A. M., Coulter, M., Russell, J., Himmelbach, A., . . . Waugh, R. (2024). Genomic resources for a historical collection of cultivated two-row European spring barley genotypes. Sci Data, 11(1), 66.

BTI publications: October – December 2023

BTI publications: October – December 2023

Abdul Halim, M. F., Fonseca, D. R., Niehaus, T. D., & Costa, K. C. (2023b). Functionally redundant formate dehydrogenases enable formate-dependent growth in Methanococcus maripaludis. J Biol Chem, 105550.

Adamala, K. P., Dogterom, M., Elani, Y., Schwille, P., Takinoue, M., & Tang, T. D. (2023). Present and future of synthetic cell development. Nat Rev Mol Cell Biol.

Baker, I. R., Matzen, S. L., Schuler, C. J., Toner, B. M., & Girguis, P. R. (2023). Aerobic iron-oxidizing bacteria secrete metabolites that markedly impede abiotic iron oxidation. PNAS Nexus, 2(12), pgad421.

Blanchard, P. L., Knick, B. J., Whelan, S. A., & Hackel, B. J. (2023). Hyperstable Synthetic Mini-Proteins as Effective Ligand Scaffolds. ACS Synth Biol, 12(12), 3608-3622.

Boatman, S., Kaiser, T., Nalluri-Butz, H., Khan, M. H., Dietz, M., Kohn, J., . . . Jahansouz, C. (2023). Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery. Gut Microbes, 15(2), 2283147.

Buller, R., Lutz, S., Kazlauskas, R. J., Snajdrova, R., Moore, J. C., & Bornscheuer, U. T. (2023). From nature to industry: Harnessing enzymes for biocatalysis. Science, 382(6673), eadh8615.

Clare, S. J., King, R. M., Tawril, A. L., Havill, J. S., Muehlbauer, G. J., Carey, S. B., . . . Altendorf, K. R. (2023). An affordable and convenient diagnostic marker to identify male and female hop plants. G3 (Bethesda).

Crone, K. K., Jomori, T., Miller, F. S., Gralnick, J. A., Elias, M. H., & Freeman, M. F. (2023a). RiPP enzyme heterocomplex structure-guided discovery of a bacterial borosin α-. RSC Chem Biol, 4(10), 804-816.

Dietz, B. R., Olszewski, N. E., & Barney, B. M. (2023). Enhanced extracellular ammonium release in the plant endophyte. Microbiol Spectr, e0247823.

Dodge, A. G., Thoma, C. J., O’Connor, M. R., & Wackett, L. P. (2023). Recombinant. mBio, e0278523.

Gehlbach, E. M., Robinson, A. O., Engelhart, A. E., & Adamala, K. P. (2023). Sequential gentle hydration increases encapsulation in model protocells. bioRxiv.

Hoops, S. L., & Knights, D. (2023). LMdist: Local Manifold distance accurately measures beta diversity in ecological gradients. Bioinformatics, 39(12).

Jang, J., & Ishii, S. (2023). Whole-genome sequence of. Microbiol Resour Announc, 12(12), e0080923.

Kalambokidis, M., & Travisano, M. (2023). The eco-evolutionary origins of life. Evolution.

Kalb, M. J., Grenfell, A. W., Jain, A., Fenske-Newbart, J., & Gralnick, J. A. (2023). Comparison of phage-derived recombinases for genetic manipulation of. Microbiol Spectr, 11(6), e0317623.

Kamer, O., Rinott, E., Tsaban, G., Kaplan, A., Yaskolka Meir, A., Zelicha, H., . . . Shai, I. (2023). Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial. Gut Microbes, 15(2), 2264457.

Kang, J. J., Ohoka, A., & Sarkar, C. A. (2023). Designing Multivalent and Multispecific Biologics. Annu Rev Chem Biomol Eng.

Lipps, S., Castell-Miller, C., Morris, C., Ishii, S., & Samac, D. (2023). Diversity of strains in the. Phytopathology.

Martinson, J. N. V., Chacón, J. M., Smith, B. A., Villarreal, A. R., Hunter, R. C., & Harcombe, W. R. (2023). Mutualism reduces the severity of gene disruptions in predictable ways across microbial communities. ISME J, 17(12), 2270-2278.

McConnell, A., Batten, S. L., & Hackel, B. J. (2023). Determinants of Developability and Evolvability of Synthetic Miniproteins as Ligand Scaffolds. J Mol Biol, 435(24), 168339.

McFarlane, J. A., Hansen, E. G., Ortega, E. C., Iskender, I., Noireaux, V., & Bowden, S. D. (2023a). A ToxIN homolog from Salmonella enterica serotype Enteritidis impairs bacteriophage infection. J Appl Microbiol, 134(12).

Park, K. H., Ordinola-Zapata, R., Noblett, W. C., Lima, B. P., & Staley, C. (2023). The effect of ultrasonic and multisonic irrigation on root canal microbial communities: An ex vivo study. Int Endod J.

Rashidi, A., Ebadi, M., Rehman, T. U., Elhusseini, H., Kazadi, D., Halaweish, H., . . . Staley, C. (2023a). Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial. Clin Cancer Res, 29(23), 4920-4929.

Reddy, S., Hu, B., & Kashani, K. (2023). Relationship between the rate of fluid resuscitation and acute kidney injury: A retrospective cohort study. Int J Crit Illn Inj Sci, 13(3), 104-110.

Revelo, X., Fredrickson, G., Florczak, K., Barrow, F., Dietsche, K., Wang, H., . . . Ikramuddin, S. (2023). Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH. Res Sq.

Souza, V., Travisano, M., & Eguiarte, L. E. (2023). The Cuatro Ciénegas Basin. Curr Biol, 33(23), R1214-R1216.

Suazo, K. F., Bělíček, J., Schey, G. L., Auger, S. A., Petre, A. M., Li, L., . . . Distefano, M. D. (2023). Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1. RSC Chem Biol, 4(11), 913-925.

Vangay, P., Ward, T., Lucas, S., Beura, L. K., Sabas, D., Abramson, M., . . . Knights, D. (2023). Industrialized human gut microbiota increases CD8+ T cells and mucus thickness in humanized mouse gut. Gut Microbes, 15(2), 2266627.

Varland, S., Silva, R. D., Kjosås, I., Faustino, A., Bogaert, A., Billmann, M., . . . Arnesen, T. (2023). N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity. Nat Commun, 14(1), 6774.

Wackett, L. P. (2023a). Microbial production of non-canonical amino acids: An annotated selection of World Wide Web sites relevant to the topics in microbial biotechnology. Microb Biotechnol, 16(12), 2401-2402.

Wackett, L. P. (2023b). Plasmids in environmental microbes: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol Rep, 15(6), 820-821.

Wackett, L. P. (2023c). Web Alert: Fungal genomes: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol, 25(10), 2054-2055.

Wackett, L. P. (2023d). Web Alert: Microbes and iodine: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol, 25(11), 2666-2667.

Wang, H., Barrow, F., Fredrickson, G., Florczak, K., Nguyen, H., Parthiban, P., . . . Revelo, X. S. (2023). Dysfunctional T Follicular Helper Cells Cause Intestinal and Hepatic Inflammation in NASH. bioRxiv.

Zhou, Y., Bi, Z., Hamilton, M. J., Zhang, L., Su, R., Sadowsky, M. J., . . . Chen, C. (2023). -Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models. Int J Mol Sci, 24(19).

A new perspective on research

A new perspective on research

A new perspective on research

Liangning Lu reflects on experiences and insights from BTI and University of Tokyo research exchange program.

By Lance Janssen

As part of an ongoing academic exchange program, colleagues from the BioTechnology Institute at the University of Minnesota and the University of Tokyo have worked together to further their research and teaching efforts since 2017. In addition to sharing research as well as hosting symposia, the exchange also brings the opportunity for graduate students to do research and train at each others’ institutions. Liangning Lu, a graduate student at the University of Tokyo, is a participant in the exchange program, conducting research with Dr. Satoshi Ishii at the U of M. We recently caught up with Lu to hear more about her time in the Twin Cities. 

What are you currently working on?
In Dr. Ishii’s lab, my current focus is on applying molecular biology techniques to better understand the mechanisms of two important steps in denitrification. I am particularly fascinated by the study of denitrifying microorganisms because N2O, as a greenhouse gas, poses a threat to the environment, and these emissions mostly originate from soil microorganisms.  

What interested you in coming to the University of Minnesota to do research?
Choosing the University of Minnesota for my research was driven by its outstanding reputation in the field of soil agronomy. The collaborative and innovative environment here aligns perfectly with my research interests. Additionally, the well-established experimental fields and faculty resources available at the University further informed my decision.

What part of your experience has stood out the most? What’s been the most challenging?
The most standout aspect of my experience has been the application of micro-sensor technology for simultaneous measurement of N2O and O2. This technique ingeniously achieves a simple and high-throughput detection of N2O. On the flip side, one of the most challenging aspects has been applying molecular biology principles to disrupt genes in microorganisms. This process involves many meticulous steps, and the need for precision in each step has given me a profound appreciation for rigorous scientific inquiry.  

What about this experience do you think is unique for visiting researchers?
What makes this experience unique for visiting scholars is that this academic visit not only facilitated meaningful academic exchange and provided me with a wealth of knowledge, but also included extensive cultural interactions. It provided me with a more comprehensive understanding of the open and egalitarian academic atmosphere in the United States, which greatly enhanced the richness of my research journey.

BTI publications: June – September 2023

BTI publications: June – September 2023

Publications by BTI faculty

Bohn, B., Chalupova, M., Staley, C., Holtan, S., Maakaron, J., Bachanova, V., & El Jurdi, N. (2023). Temporal variation in oral microbiome composition of patients undergoing autologous hematopoietic cell transplantation with keratinocyte growth factor. BMC Microbiol, 23(1), 258.

Cai, Z., Donahue, N., Jones, K. C., McNeill, K., Manaia, C., Novak, P. J., & Vikesland, P. J. (2023). Best Papers from 2022 published in the. Environ Sci Process Impacts, 25(7), 1141-1143.

Chang, Y. C., Lin, K., Baxley, R. M., Durrett, W., Wang, L., Stojkova, O., . . . Bielinsky, A. K. (2023). RNF4 and USP7 cooperate in ubiquitin-regulated steps of DNA replication. Open Biol, 13(8), 230068.

Chowdhury, S., Kennedy, J. J., Ivey, R. G., Murillo, O. D., Hosseini, N., Song, X., . . . Paulovich, A. G. (2023). Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer. Cell, 186(16), 3476-3498.e3435.

Costa, K. C., & Whitman, W. B. (2023). Model Organisms To Study Methanogenesis, a Uniquely Archaeal Metabolism. J Bacteriol, 205(8), e0011523.

El Jurdi, N., Holtan, S. G., Hoeschen, A., Velguth, J., Hillmann, B., Betts, B. C., . . . Shields-Cutler, R. (2023). Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease. Br J Haematol.

Golinski, A. W., Schmitz, Z. D., Nielsen, G. H., Johnson, B., Saha, D., Appiah, S., . . . Martiniani, S. (2023). Predicting and Interpreting Protein Developability Via Transfer of Convolutional Sequence Representation. ACS Synth Biol, 12(9), 2600-2615.

Gralnick, J. A., & Bond, D. R. (2023). Electron Transfer Beyond the Outer Membrane: Putting Electrons to Rest. Annu Rev Microbiol, 77, 517-539.

Hassan, A. Z., Ward, H. N., Rahman, M., Billmann, M., Lee, Y., & Myers, C. L. (2023). Dimensionality reduction methods for extracting functional networks from large-scale CRISPR screens. Mol Syst Biol, e11657.

Hill, E. R., Chun, C. L., Hamilton, K., & Ishii, S. (2023). High-Throughput Microfluidic Quantitative PCR Platform for the Simultaneous Quantification of Pathogens, Fecal Indicator Bacteria, and Microbial Source Tracking Markers. ACS ES T Water, 3(8), 2647-2658.

Hu, L. S., D’Angelo, F., Weiskittel, T. M., Caruso, F. P., Fortin Ensign, S. P., Blomquist, M. R., . . . Tran, N. L. (2023). Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures. Nat Commun, 14(1), 6066.

Huang, S., Bergonzi, C., Smith, S., Hicks, R. E., & Elias, M. H. (2023). Field testing of an enzymatic quorum quencher coating additive to reduce biocorrosion of steel. Microbiol Spectr, e0517822.

Justyna, K., Das, R., Lorimer, E. L., Hu, J., Pedersen, J. S., Sprague-Getsy, A. M., . . . Distefano, M. D. (2023). Synthesis, Enzymatic Peptide Incorporation, and Applications of Diazirine-Containing Isoprenoid Diphosphate Analogues. Org Lett, 25(36), 6767-6772.

Kalambokidis, M., & Travisano, M. (2023). Multispecies interactions shape the transition to multicellularity. Proc Biol Sci, 290(2007), 20231055.

Kong, W., Qiu, L., Ishii, S., Jia, X., Su, F., Song, Y., . . . Wei, X. (2023). Contrasting response of soil microbiomes to long-term fertilization in various highland cropping systems. ISME Commun, 3(1), 81.

Lane, B. R., Anderson, H. M., Dicko, A. H., Fulcher, M. R., & Kinkel, L. L. (2023). Temporal variability in nutrient use among Streptomyces suggests dynamic niche partitioning. Environ Microbiol.

Li, J., Arnold, W. A., & Hozalski, R. M. (2023). Spatiotemporal Variability in. Environ Sci Technol, 57(37), 13959-13969.

Lu, M., Lee, Z., Lin, Y. C., Irfanullah, I., Cai, W., & Hu, W. S. (2023). Enhancing the production of recombinant adeno-associated virus in synthetic cell lines through systematic characterization. Biotechnol Bioeng.

McConnell, A., & Hackel, B. J. (2023). Protein engineering via sequence-performance mapping. Cell Syst, 14(8), 656-666.

Miley, K., Meyer-Kalos, P., Ma, S., Bond, D. J., Kummerfeld, E., & Vinogradov, S. (2023). Causal pathways to social and occupational functioning in the first episode of schizophrenia: uncovering unmet treatment needs. Psychol Med, 53(5), 2041-2049.

Morra, A., Schreurs, M. A. C., Andrulis, I. L., Anton-Culver, H., Augustinsson, A., Beckmann, M. W., . . . Investigators, k. (2023). Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer Med, 12(15), 16142-16162.

Ndinga-Muniania, C., Wornson, N., Fulcher, M. R., Borer, E. T., Seabloom, E. W., Kinkel, L., & May, G. (2023). Cryptic functional diversity within a grass mycobiome. PLoS One, 18(7), e0287990.

Qualls, D. A., Lambert, N., Caimi, P. F., Merrill, M. H., Pullarkat, P., Godby, R. C., . . . Salles, G. A. (2023). Tafasitamab and lenalidomide in large B cell lymphoma: real-world outcomes in a multicenter retrospective study. Blood.

Sakai, A., Jonker, A. J., Nelissen, F. H. T., Kalb, E. M., van Sluijs, B., Heus, H. A., . . . Huck, W. T. S. (2023). Cell-Free Expression System Derived from a Near-Minimal Synthetic Bacterium. ACS Synth Biol, 12(6), 1616-1623.

Seabloom, E. W., Caldeira, M. C., Davies, K. F., Kinkel, L., Knops, J. M. H., Komatsu, K. J., . . . Borer, E. T. (2023). Globally consistent response of plant microbiome diversity across hosts and continents to soil nutrients and herbivores. Nat Commun, 14(1), 3516.

van Hees, D., Hanneman, C., Paradis, S., Camara, A. G., Matsumoto, M., Hamilton, T., . . . Kodner, R. B. (2023). Patchy and Pink: Dynamics of a Chlainomonas sp. (Chlamydomonadales, Chlorophyta) algal bloom on Bagley Lake, North Cascades, WA. FEMS Microbiol Ecol.

Vitt, J. D., Hansen, E. G., Garg, R., & Bowden, S. D. (2023). Bacteria intrinsic to Medicago sativa (alfalfa) reduce Salmonella enterica growth in planta. J Appl Microbiol, 134(9).

Wackett, L. P. (2023a). A microbial evolutionary approach for a sustainable future. Microb Biotechnol, 16(10), 1895-1899.

Wackett, L. P. (2023b). Acid stress in microbes: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol Rep, 15(4), 335-336.

Wackett, L. P. (2023c). Cyanobacterial algal blooms: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol, 25(7), 1375-1376.

Wackett, L. P. (2023d). Microbes at low substrate concentrations: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol, 25(6), 1218-1219.

Wackett, L. P. (2023e). Web alert: Fabrication with microbial spores: An annotated selection of World Wide Web sites relevant to the topics in Microbial Biotechnology. Microb Biotechnol, 16(10), 2007-2008.

Wackett, L. P. (2023f). Web Alert: Solvent stress on environmental microbes: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology. Environ Microbiol, 25(8), 1563-1564.

Wackett, L. P. (2023g). Web alert: Two-phase biocatalysis. Microb Biotechnol, 16(8), 1702.

Wackett, L. P., & McKnight. (2023). Web alert: Microbial biofilm catalysis. Microb Biotechnol, 16(7), 1577-1578.

Wang, H., Feyereisen, G. W., Wang, P., Rosen, C., Sadowsky, M. J., & Ishii, S. (2023). Impacts of biostimulation and bioaugmentation on woodchip bioreactor microbiomes. Microbiol Spectr, e0405322.

Wang, Q. Q., Sun, M., Tang, T., Lai, D. H., Liu, J., Maity, S., . . . Long, S. (2023). Functional screening reveals. mBio, 14(4), e0130923.

Wang, Z., Ishii, S., & Novak, P. J. (2023). Quantification of depth-dependent microbial growth in encapsulated systems. Microb Biotechnol.

Worner, K., Liu, Q., Maschhoff, K. R., & Hu, W. (2023). Identification of RNA-binding proteins’ direct effects on gene expression via the degradation tag system. RNA, 29(10), 1453-1457.

Zhang, Q., Xuan, Q., Wang, C., Shi, C., Wang, X., Ma, T., . . . Chen, C. (2023). Bioengineered “Molecular Glue”-Mediated Tumor-Specific Cascade Nanoreactors with Self-Destruction Ability for Enhanced Precise Starvation/Chemosynergistic Tumor Therapy. ACS Appl Mater Interfaces, 15(35), 41271-41286.

Zhang, W., Dong, H., Wang, X., Zhang, L., Chen, C., & Wang, P. (2023). Engineered. ACS Appl Mater Interfaces.

Zhu, B., Du, Z., Dai, Y., Kitaguchi, T., Behrens, S., & Seelig, B. (2023). Nanodroplet-Based Reagent Delivery into Water-in-Fluorinated-Oil Droplets. Biosensors (Basel), 13(8).

Zlotorzynska, M., Chea, N., Eure, T., Alkis Ramirez, R., Blazek, G. T., Czaja, C. A., . . . Grigg, C. T. (2023). Residential social vulnerability among healthcare personnel with and without severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in Five US states, May-December 2020. Infect Control Hosp Epidemiol, 1-7.

Modeling microbial complexity

Modeling microbial complexity

Modeling microbial complexity

Will Harcombe combines experimental and computational models to decode complex microbial interactions.

By Bernard Cook III

The role of E. coli in causing food-borne illness is well known. Less well known, however, is the way microbes interact with each other. Like humans, they exchange resources and live in communities. Understanding these complex interactions could help scientists predict and even control the properties of a microbial community—yielding new tools for treating infections, promoting human and animal health, and improving soil productivity. 

Will Harcombe, an associate professor of Ecology, Evolution and Behavior and a member of the BioTechnology Institute, studies microbial interaction by looking at the exchange of chemicals among microbial species. “One of the fundamental ways [microbes] can influence each other is just by taking up and releasing chemicals into the environment,” he says. “Will they compete by trying to eat the same resource? Or will they facilitate each other by one secreting a product that helps another?”

Model Behavior

To make sense of microbial interactions, Harcombe starts with a model of how he expects microbes to interact. At its core, a model is a tool that describes how the output of a system depends on its inputs. Harcombe’s models consist of equations that relate the abundance of two microbial species, the output, to defined inputs like available nutrients and spatial distribution. Using the model, he can test what happens to the abundance of two microbial species when placed in an environment with defined nutrients. Importantly, this allows him to observe what the microbes do when they interact in the ways he suspects.

After generating computer-based results, Harcombe replicates this experiment in the lab.  Harcombe places two or more species of microbes together and tracks the resources they exchange. At the same time, he observes population-level characteristics such as growth rates, colony shape and species abundance. By simultaneously monitoring resources and community traits, he can answer questions about the spatial organization, the ratio between species and how available nutrients impact the exchange of resources. 

Sometimes experiments align with the results generated by his model. In other cases, they differ from — or even contradict — the model.

Two-Species Surprise

In one study, Harcombe and his colleagues wanted to investigate the dynamics between two microbial species, each of which depends on the other for survival. One (E. coli) was modified to require a nutrient—methionine—produced by the other (S. enterica). S. enterica, for its part, needs acetate excreted by E. coli.

One might expect these microbial colonies would thrive when cultured together — and when cultured alone, neither would make it. Per his computer model, that’s precisely what happened. When cultured in the lab, he saw the same results.

 Then came a surprise. In the lab, Harcombe introduced a virus that infects one species but not the other. Because each species’ survival depends on the other, Harcombe expected that infection would impact both. 

When he introduced a virus that only infected S. enterica, his prediction was spot on. When he introduced a virus that only infected E. coli, he ended with fewer E. coli as predicted, but surprisingly, he also found more S. enterica relative to pre-infection numbers. What was he missing?

Answering that question experimentally would have required painstaking tests, altering one variable at a time until he understood what was happening. While that approach might eventually provide an answer, it would be costly. Without knowing which explanations were plausible, Harcombe could spend years testing possible mechanisms responsible for the odd result. 

Productive Insights

Enter modeling. If the microbes weren’t behaving the way he expected, there must be something else; different metabolites or different types of interactions to explain the observations. So rather than running experiments to identify the mechanisms at play, Harcombe put those possibilities into the model. Once he found a model approximating his observation, he could confirm his conjecture with additional experimentation.

Harcombe suspected some E. coli developed resistance to the virus, protecting them from extinction. He further postulated that others would burst and release a wealth of nutrients. Together, they might provide an abundance of the acetate S. enterica need to thrive. Incorporating these mechanisms into his model yielded results that closely mirrored the experimental model.

“The biggest surprise to me in this study is that bacteria could get the elements they needed from other species by eating the dead,” says Harcombe.

Back in the lab, Harcombe ran additional experiments to test the model. For the most part, they supported his hypothesis. The only thing missing was a second consequence of E. coli developing a resistance to the virus. Virus-resistant E. coli produced more acetate than their nonresistant counterparts.

Harcombe is pleased with the way the experiment-plus-model approach has boosted his ability to solve microbial mysteries, and how the solutions stand to benefit humanity. Harcombe and colleagues use these models to predict how microbes respond to antibiotics and engineer interactions into microbial communities in soils to render crops more resilient to a changing climate. “Going forward, I’m really optimistic that we will be able to continue to develop our understanding of fundamental processes and apply it in these different areas.”