Faculty Research Insight Talks #4

Mike Travisano

Ecology and Environmental Biology
University of Minnesota

Microbial days of future passed

Mike Smanski

Biochemistry, Molecular Biology and Biophysics
University of Minnesota

Lord of the ring-species

The students and post-docs in my lab work on a group of diverse and seemingly unrelated research and enginering projects.

In this short talk, I will attempt to link them all together in a cohesive way to highlight (i) what we are interested in and (ii) the at-times-serendipitous benefits of a broad research program.

I will talk about soil microbiomes, neuroprotective small molecules, gene drives, sustainable aviation fuel, and glowing carp.

I won’t talk about the weird smell coming out of Gortner 379 (and neither should you; still top secret). This will be a high-level talk, so please ask follow-up questions if you want to hear the details.

THURSDAY I FEB. 16 I 3:30-4:30 PM CST I HYBRID SEMINAR

Faculty Research Insight Talks #3

Burckhard Seelig

Biochemistry, Molecular Biology, and Biophysics
University of Minnesota

Imagine the time before there were proteins

The Seelig group investigates the emergence and early evolution of proteins at the origin of life.

We apply high-through-put methods of selection and directed evolution to generate artificial proteins that nature has never seen before. Those proteins help us better understand how the first ever proteins could have appeared or how the genetic code may have evolved.

Besides studying these fundamental science questions, we are also interested in applying directed evolution to create enzymes as “designer catalysts” to harness the power of enzymes for the synthesis of chemicals and pharmaceuticals, and for biomedical applications.

Bo Hu

Bioproduct & Biosystems Engineering
University of Minnesota

Process development for bioproducts generation & nutrients recycle from agricultural wastes

Nutrients, such as nitrogen (N), phosphorous (P), and sulfur (S), are vital components for fertilizers and animal feeds, while they are also the major pollutants from rural domestic wastewater and agricultural manure.

Improving utilization efficacy of these nutrients in animal feeds and recycle these nutrient pollutant from rural and agricultural wastes can minimize the environmental impacts of agricultural activities, alleviate the dependency on fossil fuels, and bring benefits to local communities.

Dr. Bo Hu will introduce his research at University of MInnesota related to this area, emphasizing on biomass utilization, industrial fermentation and agricultural waste management. His research group is currently working on projects to improve nutritional value of animal feeds via fungal fermentation, remove phosphorus, nitrogen and sulfur from agricultural waste and sewage sludge via different approaches, including microbial electro-chemical cells and re-design of anaerobic digestion.

In this presentation, he will explain several case studies in the process development for nutrients removal and recycle.

THURSDAY I FEB. 9 I 3:30-4:30 PM CST I HYBRID SEMINAR

Faculty Research Insight Talks #2

Alptekin Aksan

Mechanical engineering
University of Minnesota

Design & manufacturing of active biomaterials for biotechnology applications

My research focuses on two interwoven areas: bioencapsulation, and biopreservation. In biopreservation area, I focus on establishing the low-temperature and low-hydration physicochemical transitions of the solution environment on the stability of macromolecules and cells.

In bioencapsulation area, I focus on developing synthetic organic materials for a wide range of applications including bioremediation, biocatalysis, and self-healing materials.

Larry Wackett

Biochemistry, Molecular Biology, and Biophysics
University of Minnesota

Enzymes for PFAS, pesticides, phramaceuticals & pools

The Wackett lab focuses on unconventional enzymes and their real-world implementation. We have discovered the enzymes making b-lactones and biodegrading PFAS, prominent pharmaceutical pollutants, and a water disinfection chemical. I will talk about the biodegradative enzymes, one of which is now being produced at multi-ton scale.

THURSDAY I FEB. 2 I 3:30-4:30 PM CST I HYBRID SEMINAR

Q&A with BTI Director Claudia Schmidt-Dannert

As the BioTechnology Institute’s new director, longtime faculty member Claudia Schmidt-Dannert aims to plant the institute firmly on the front lines of emerging needs and opportunities.

By Mary Hoff

Two decades ago, Claudia Schmidt-Dannert knew exactly where she wanted to be: at the frontlines of the intersection of biology and technology. And that meant joining the faculty of the University of Minnesota’s BioTechnology Institute. “BTI is actually one of the reasons I came to the University of Minnesota, because of this interaction between life sciences and engineering,” she says. “That’s very unique here.”

Named BTI director in January of this year, Schmidt-Dannert is working not only to strengthen interdisciplinary ties within the community as it recovers from disruptions due to the Covid pandemic, but also to firmly establish BTI’s position at the frontlines of biotechnology research and application during what could be the field’s most exciting times yet.

What do you hope to accomplish as director?

My focus is on keeping pace with biotechnology, really thinking about, “What are the next big things?” For example, biomanufacturing, biofabrication, new types of functional biomaterials for a range of applications—this is the future. We really must position ourselves very well in this space, make sure we are at the forefront of these types of efforts in biotechnology research, applied science, and development. We need to make sure we have the right people, resources and get people to collaborate across disciplines on these topics. We want to be spearheading new developments in biotechnology, looking at what biology can do to improve our future.

What strengths do you bring to the role?

I have a broad research background. I’m working both in fundamental areas of biotechnology but also in the engineering space, and my research spans from molecules to systems. I’m also very applied-minded. And I maybe bring a little bit more of a fresh perspective. We have a strong focus in bioremediation and environmental aspects of biotechnology. There are other and emerging focus areas in biootechnology that we should pay attention too and emphasize more. Also, I like collaboration and community-building. This is very important with a variety of stakeholders.

How important will BTI’s role in workforce training and strengthening Minnesota’s biotechnology be under your administration?

Most of our undergraduate and graduate students as well as postdocs will not follow an academic or medical career and instead many will seek out other employment in industry. There is high demand for skilled individuals from the biotechnology and biomanufacturing sector. We need to make sure that our students and postdocs are well prepared for these good-paying jobs. Over the past few years, BTI has collaborated with industrial partners on workforce development. I see this as an area that should be expanded. In addition, I feel strongly that meaningful biotechnology training should be incorporated at the undergraduate levels—where BTI can contribute. BTI also administers a small masters-level graduate program in microbial engineering that is aimed at students that want to go into industry. The student and postdoc-level workshop series as well as workshops offered through our NIH Biotechnology training program provide additional career relevant, professional skill sets.

Where do you see the big opportunities in the years ahead?

Biotechnology is very broad field, so there are many opportunities for different types of research. For example, synthetic biology is experiencing an influx of many new ideas in areas like materials sciences, sustainable biomanufacturing, artificial intelligence and computing. Addressing climate change, developing a circular bioeconomy, biomanufacturing and biofabrication—that’s where I see a lot of opportunities.

We also have very unique resources in Minnesota that go beyond our strong medical and agricultural industries. Northern Minnesota is rich in forests, water and minerals. My goal is to look at these resources as well as associated societal and environmental challenges associated with accessing these resources from a biotechnology perspective. I believe that there are many unique Minnesota-specific opportunities for biotechnology and bioeconomy development in our state.

What do you see as growth areas for the Institute?

I would like to continue building momentum and strength in synthetic biology. We have a research cluster in this area, but we have to further ramp up our expertise in this area. We are also lacking in certain cell-based manufacturing systems, especially for pharmaceuticals and biologics – we are not particularly strong in this area. Right now. we’re focused mostly on microbial systems with the new BRC [Biotechnology Resource Center] Microbial Cell Production Facility. But I also think mammalian cell cultures offer new opportunities for research. We need to bring in more young faculty with expertise in these areas.

Another goal is to build community, facilitate social interactions and provide more opportunities to exchange ideas among biotechnology research labs—crossing disciplines but also campuses. That was all put aside during Covid times, but it is very important. Without community, BTI is nothing but a collection of people. We’re going to have seminars followed by networking happy hours in both St. Paul and Minneapolis, not just by bringing in external speakers but having BTI labs give short talk to present their current research and where there research is headed. We are also reviving the graduate student and postdoc-led workshop series.

How will the Biotechnology Resource Center expansion benefit the University and for the state?

The new Microbial Cell Manufacturing Facility will have six times the pace of the current BRC, which will bring much needed capacity in microbial biomanufacturing to the University. Currently, the BRC is operating at capacity and even must turn down biomanufacturing projects and clients because of this. There is a huge demand for the types of the service the BRC offers in the preclinical space. The expanded BRC will therefore be able to serve much better the needs of UM researchers, industry, and academic partners. The “old BRC” offers opportunities for the development of new workforce training programs in biomanufacturing.

What are the big emerging societal needs that biotechnology can address, and how is BTI positioning to address them?

It is clear that we need to find drastically new ways of mitigating climate change, by developing new bio-based technologies for sustainable manufacturing, energy conversion, combating greenhouse gas emission or converting and sequestering carbon dioxide and for addressing environmental concerns. I see BTI as a catalyst and facilitator of research in these areas by bringing people together to tackle ambitious problems as teams with diverse cross-disciplinary skill sets.

Faculty Research Insight Talks #1

Daniel Bond

Plant and Microbial Biology, Microbiology
University of Minnesota

We need to talk about nanowires

For nearly two decades, biological electron transfer research was dominated by the hypothesis that Geobacter pili form conductive nanowires. Cryo-electron microscopy has now revealed their structure. Not everybody is happy.

Jeff Gralnick

Plant and Microbial Biology
University of Minnesota

Shewanella– You don’t know the power of the dark side

Shewanella is an environmental bacterium capable of breathing more compounds than any other organism identified on Earth. Many of these substrates are found naturally in insoluble oxide minerals, meaning they must take electrons from central metabolism and move them outside the cell.

Here I will describe surprising functions for extracellular electron transfer proteins in what might be a respiration over-drive system and a multiheme cytochrome that is a receptor for bacteriophage.

THURSDAY I JAN. 26 I 3:30-4:30 PM CST I HYBRID SEMINAR

Keith Hengen

Keith Hengen

Assistant Professor of Biology
Washington University

Circuit-specific flickering of sleep & wake predicts natural behaviors: the minimal unit of brain sleep

Sleep and wake are understood to be slow, long-lasting processes that span the entire brain. The possibility that local circuits throughout the brain might routinely and independently switch between sleep and wake has been difficult to address due to reliance on surface measurements of brain rhythms to classify state.

By recording high resolution neural activity across diverse regions of the murine brain for 24 h, we learn reliable rules of sleep/wake embedding in each circuit at the scale of 100 microseconds and 100 microns, a 7 order of magnitude improvement in resolution over standard approaches.

We show that diverse microcircuits regularly switch between sleep-like and wake-like states (flickers), independent of the rest of the brain and the arousal state of the animal. Furthermore, high sleep pressure suppresses wake flickers within sleep, but does not modulate sleep flickers during wake. In contrast, sleep flickers during complex, natural behavior results in a momentary pause of movement.

Our results reveal that sleep and wake arise from an unstable patchwork of states throughout the brain.

THURSDAY I DEC. 8 I 3:30-4:30 PM CST I HYBRID SEMINAR

Katherine Davis

Katherine Davis

Assistant Professor of Chemistry, Physics graduate Program member
Emory College

Structural insights into the biosynthesis and bioactivity of natural products

Natural products provide a powerful foundation from which to develop novel therapeutics. Despite their utility, our understanding of both their biosynthesis and mechanisms of action are often incomplete, due in part to the scarcity of structural data depicting their interactions with associated bio-synthetic enzymes and/or targets.

Ribosomally synthesized and post-translationally modified peptides (RiPPs), for example, are a diverse class of bioactive peptides whose simple biosynthetic pathways make them attractive for bio-engineering efforts. However, the structural basis for substrate recognition and recruitment by their respective tailoring enzymes remains unclear. Hydroxyalkylquinolines (HAQs), by contrast, have been studied extensively for their marked antimicrobial activity, yet insights into the origin of this activity are limited.

In this talk, I will present X-ray crystallographic data and computational modeling studies that elucidate the structure and dynamics of associated enzyme-ligand interactions. In particu-
lar, our results provide new insights into the role of a putative substrate-
binding domain associated with RiPP-biosynthesis via study of the radical S-adenosylmethionine (SAM) enzyme, SuiB, and confirm the hypothesis that competition with the co-substrate ubiquinone is the basis for dihydroorotate dehydrogenase inhibition by bacterial HAQs.

THURSDAY I NOV. 10 I 3:30-4:30 PM CST I HYBRID SEMINAR

Synthetic Cells and Biofactories

Kate Adamala and the Build-a-Cell consortium look to synthetic biology for insight into the origins of life and a source for vital raw materials.

By Bernard Cook III

Your phone, your food, and the fuel that powers your car all depend on oil-derived petrochemicals. But experts anticipate oil reserves will run dry as early as 2070, forcing industries dependent on petrochemicals to look for alternatives that would fundamentally change the way they do business–and the way we live.

But scientists like Kate Adamala (BTI/Genetics, Cell Biology and Development) see another path forward. They envision a world where oil reserves disappear but one where we’ll still be able to meet our need for petrochemicals. Their solution? Create more life.

Adamala, a chemical engineer by training, is working to build living organisms from nonliving chemical components. These “synthetic cells” can help scientists explore the origin of life, accelerate drug discovery, or provide a renewable source of resources, like petrochemicals.

At its core, a synthetic cell is an organism that exhibits lifelike qualities. Much like a car, which is a collection of metal parts until arranged in the right way, cells are chemical bundles organized in a particular manner. Adamala constructs synthetic cells in her lab by encapsulating nucleic acids, amino acids, and ribosomes (the building blocks of cellular life) within a protective lipid coating. This method, known as the “bottom-up” approach, offers a key advantage: complete control over the cell’s components.

Natural cells can also be engineered to perform specific functions, but they’re resistant to change, and coaxing them into producing large quantities of desirable chemicals comes at a cost. When scientists engineer cells to create petrochemicals, for example, the build-up of those chemicals can damage the cell. “No self-respecting cell will make those chemicals because it’s toxic to them.”

Synthetic cells, however, are a blank slate. “Because we make them from scratch, they don’t have the baggage of 4 billion years of evolution,” Adamala remarks. They can be manufactured to do what scientists want them to do (like churning out petrochemicals). But, even with this level of control, there are still compromises. Adamala likens this to canine domestication. “I want my dog to sit on my lap and keep me warm in the winter. And he does that, but he cannot go out and hunt … so that’s the trade-off we made.”

Before synthetic cells can support a robust biomanufacturing economy, scientists like Adamala also need to resolve the physics of how cells self-replicate. To date, researchers have yet to determine how to make synthetic cells reproduce on their own–a crucial step toward using these organisms as in mini, living biofactories.

Like many scientists, Adamala grew up watching science fiction films and was fascinated by the search for life beyond earth. She earned her Ph.D. in astrobiology, but synthetic biology allowed her to explore her passion while producing tangible benefits for society. “The synthetic cell engineering field presented itself as everything I always wanted. It has connections to origins and astrobiology, so I can still say I’m looking for life on Mars! But it’s also incredibly applicable. It could solve some of the biggest problems our economy is facing now.”

Adamala isn’t the only scientist excited about this approach to cell engineering. The Build-a-Cell consortium, co-founded and led by Adamala, intends to construct a network of scientists sharing ideas, data, success stories, and failures–not unlike open-source software platforms that depend on shared knowledge to drive innovation. Adamala is hopeful that by uniting researchers via Build-a-Cell, they’ll get there sooner rather than later.

Once we unlock their potential, synthetic cells could produce fuel for our cars, fibers for clothing, and fertilizers to increase crop yields. They may also accelerate biomedical discovery or offer a glimpse into the life of our earliest ancestors. One day, they may even enable us to survive on Mars.

Fixen Lab

Fixen Lab

University of Minnesota

A ‘Fix’-ing to understand electron flow in a purple nonsulfur bacterium

Bacteria are promising biocatalysts for the production of biofuels and bioproducts because they can tap into sources of energy that we are still struggling to use (e.g. plant biomass, sunlight, and waste streams), and the ATP and electrons generated from metabolizing these sources can power metabolic pathways that produce energy-rich
compounds.

Anaerobic bacteria and archaea, in particular, have evolved diverse ways of managing electron flow to pathways that often naturally result in the release of compounds like butanol, ethanol, methane, hydrogen, etc. Understanding mechanisms that control electron flow is necessary to get these organisms to produce more of these com-
pounds.

In the Fixen lab, we are working to understand electron flow in the anoxygenic phototroph, Rhodopseudomonas palustris, by:

1.characterizing components of electron transfer and factors that determine their interactions;

2.) understanding how these components are regulated by environmental factors; and

3.) identifying and characterizing new pathways that can use these electrons to make valuable compounds.

By understanding how R. palustris controls electron flow, we hope to find new ways to divert more electrons down pathways that generate energy-rich compounds.

THURSDAY I OCT. 27 I 3:30-4:30 PM CST I HYBRID SEMINAR

Harcombe Lab

Harcombe Lab

Associate Professor, Ecology, Evolution and Behavior
University of Minnesota

A metabolic approach to microbial community robustness

As we strive to manage critical microbial communities we must understand how these systems respond to perturbation. We use a combination of metabolic modeling and laboratory co-cultures to investigate how the physiology of cells determines the content, function and dynamics of microbial communities.

We have found that cross-feeding tends to stabilize species ratios, but makes community growth less robust to perturbations. We specifically investigate the impact of antibiotics, bacteriophage and mutations in a system in which Escherichia coli and Salmonella enterica rely on each other for essential metabolites.

Our work suggests that metabolic interactions between species can have predictable impacts on both ecological and evolutionary responses to perturbation in microbial communities.

THURSDAY I OCT. 20 I 3:30-4:30 PM CST I HYBRID SEMINAR