The DNA Solution

Synthetic biology is poised to revolutionize everything from health care to climate change—and Michael Smanski is making the most of it.

By Mary Hoff

The exploding yeast and fluorescent fish are interesting, for sure. But for Michael Smanski, the real attraction of synthetic biology is the chance to work at the cusp of a new era in biology—one that holds promise for improving food production, medical care, climate change adaptation, pollution cleanup and more.

Living things use DNA as a template for creating proteins, which in turn control the processes that make life possible. Synthetic biology creates new forms of DNA and enlists microbes, plants, or other organisms to use these new forms to produce products or functions beneficial to humans.  

“Twenty years ago, the field of biology went through an interesting phase change that was catalyzed by the Human Genome Project: the ability to read DNA. And it touched every area of biology,” says Smanski, McKnight Land Grant professor in the College of Biological Sciences “The phase change we’re going through now is even more exciting than that—and that’s the ability to write with DNA. It’s changing biology from a descriptive science, where we’re trying to learn about nature, to an engineering science, where we can ask, ‘What can life be programmed to do?’”

In Smanski’s case, the answer to that question appears virtually boundless. Trained as a biochemist and bacteriologist, he came to the University in 2014 because of its strength in both engineering and the natural sciences. In the few short years since, both synthetic biology and his research have expanded dramatically. Assembling a team of postdoctoral fellows and graduate students with expertise in computer science, chemistry and engineering as well as biology, he began exploring strategies for creating DNA-based assembly lines that microbes could use to make materials useful for humans.

In one line of research, he and his colleagues have been working to optimize a bacteria-based system that produces drugs to treat disorders such as stroke or Parkinson’s disease. In another, he has led development of a novel strategy for ensuring that engineered organisms can’t produce viable progeny with their wild relatives (hence the exploding yeast).

More recently, Smanski has begun applying synthetic biology to more complex organisms, such as vascular plants, insects, and vertebrates. By modifying their genomes to incorporate useful traits while also removing their ability to breed with unmodified relatives, he’s creating innovative strategies for controlling disease-causing and ecosystem-disrupting pests without resorting to poisons.

“We have a few projects in plants to try to translate this for agriculture,” he says. Novoclade, a University biotech startup he helped found and for which he serves as chief technology officer, is exploring applications for controlling mosquitoes and stopping the spread of invasive carp (hence the fluorescent fish).

Some of the biggest challenges related to his work are not about altering molecules and coaxing them to perform desired tasks. Rather, they relate to the kinds of issues entrepreneurs encounter with any new technology: making sure they’re addressing real needs; identifying and mitigating potential unintended consequences, complying with regulatory constraints, listening and incorporating input from various stakeholders, scaling, and more. So, for instance, he’s involved in a national Manufacturing Innovation Institute called BioMADE that’s working to bridge the large and often unwieldy gap between being able to do something in a laboratory and being able to do it on a commercial scale. And he’s consulting with the Minnesota Department of Natural Resources, tribal governments, and others to ensure their concerns are addressed and their needs are met with his carp work.

“We think a lot about translating these technologies to the field and trying to do it responsibly, because we don’t want to develop a technology that the public doesn’t want,” he says. “We’re not just teaching people, we’re learning from them in ways that helps guide the direction that we take.”

As he sets his sights on new directions, Smanski is excited about the College of Biological Sciences’ recently announced efforts to make the University of Minnesota an international hub for frontline synthetic biology research and development. 

“We’re excited to see the details emerge,” he says. “There are so many interesting directions that the field can take right now”—from advancing and applying the new tools to engineering a person’s cells to fight cancer, to reducing waste in food production, producing materials to replace climate-disrupting fossil fuels, developing crops that can thrive in the face of climate change and more.

As far as what’s next for the Smanski lab—even Smanski himself suspects it’s beyond imagination.

“Throughout my career and throughout the time frame of my lab, we let the science take us in the most interesting directions,” he says. “We’re going to keep going where the science leads us.”

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.”