“Legacy Phosphorus” and Our Waters

For decades, phosphorous has accumulated in Wisconsin soils. Though farmers have taken steps to reduce the quantity of the agricultural nutrient applied to and running off their fields, a new study reveals that a “legacy” of abundant soil phosphorus has a large, direct and long-lasting impact on water quality.

The study, published in the journal Ecosystems and focused on southern Wisconsin’s Yahara watershed, may be the first to provide quantifiable evidence that eliminating the overabundance of phosphorus will be critical for improving the quality of the state’s lakes and rivers.

For example, the results indicate that a 50 percent reduction in soil phosphorus in the Yahara watershed’s croplands would improve water quality by reducing the summertime concentration of phosphorus in Lake Mendota, the region’s flagship lake, by 25 percent.

“If we continue to apply phosphorus at a greater rate than we remove it, then phosphorus accumulates over time and that’s what’s been happening over many decades in the Yahara watershed,” says Melissa Motew, the study’s lead author. Motew, working with CALS agronomy professor and co-author Christopher Kucharik, is a doctoral candidate at the UW–Madison Nelson Institute for Environmental Studies.

Phosphorus seeps into soils primarily by way of fertilizer and manure, and what crops and other plants don’t use to grow then leaks into waterways with rain and snowmelt runoff. Scientists have long believed that excess soil phosphorus is a culprit behind the murky waters and smelly algal blooms in some of Wisconsin’s lakes and rivers.

Conventional efforts, like no-till farming and cover crops, have tried to address nutrient runoff by slowing its movement from soils to waterways. However, the study shows that simply preventing runoff and erosion does not address the core problem of abundant soil phosphorus, and this overabundance could override conservation efforts.

“Solutions should be focused on stopping phosphorus from going onto the landscape or mining the excess amount that is already built up,” says Kucharik.

Using newly advanced computer models, the study shows the watershed has about four times more phosphorus in its soil than is recommended by UW–Extension, which writes the state’s nutrient management recommendations based on what crops need and a landscape’s potential for nutrient runoff.

Currently, the only method known to draw down soil phosphorus is harvesting crops, but Kucharik explains that plants take up only a small amount of the surplus each year.

“It is unlikely that any cropping system will quickly draw down the excess,” he says.

It will require working with farmers to practice better nutrient accounting and counter the tendency of some to apply more fertilizer, as an insurance measure, than is needed.

Food production need not be compromised by potential solutions, Kucharik says. There is enough excess phosphorus in our soils “to support plant nutrient needs for a long time.”

The research, funded by the National Science Foundation, is part of UW–Madison’s Water Sustainability and Climate project.

The “Icing” on the DNA

XUEHUA ZHONG, an assistant professor of genetics, studies epigenetics, a growing area of research focused on how chemical tags on DNA can change the expression of genes. She and her team at the Zhong Lab of Epigenetic Regulation, located at the Wisconsin Institute for Discovery, are especially interested in the modification of genes involved in growth and development, and how epigenetics can be affected by the changing environment.

As evidence for a link between environmental factors and epigenetics grows, so does public interest in the topic as people consider the impact of their lifestyles and diets not only on themselves but also on the next generation. Zhong and her team hold talks for the public about their work and conduct a number of hands-on programs about epigenetics for undergraduate and K-12 students, including a summer science camp for local high school students, a field trip for middle-schoolers, a youth apprenticeship program in her lab and a “tabletop exploration station” about how lifestyle choices can affect gene expression. Zhong hopes opportunities such as these will raise interest in and encourage the next generation to study this rapidly growing field.

What is epigenetics?

It’s a very interesting question, I would say. The definition of epigenetics has been really challenging over the years because there are different concepts of epigenetics. Most people accept the definition that epigenetics is modifications on the genetic material, the DNA, that changes expression of the underlying genes. I like to say that epigenetics is like a Christmas decoration. You decorate the DNA in a different way, and then the expression of genes is different.

I would also use another comparison: If you think about a cake, the base of the cake is the DNA, the genes. Then the epigenetics is the frosting, the decoration on the cake. And the nice thing about that is if you don’t like the frosting, you can remove it. You can redecorate it differently, and it looks like a different cake.

Can epigenetics be passed on from one generation to the next?

This is another reason why epigenetics is so debatable—the question of inheritance. The modification on top of DNA has been well accepted, but whether it’s heritable is still being debated. Some modifications are very transient and unstable. But some of the modification, for example, methylation—the process of adding methyl groups to the DNA molecule—is fairly stable and can be inherited by the next generation. That is called transgenerational inheritance.

We talk a lot about how your diet, your exercise and your environment have a huge impact on you, obviously, but can also impact your children and even grandchildren through transgenerational inheritance. There are cases from World War II of women who lived through famine, and even 20 years later when they were leading a healthier life, those women tended to have children with more diseases and stress through- out life.

How is this inheritance being studied?

It’s very challenging to study transgenerational inheritance in humans. We’re talking about 60, 70 or 80 years for each generation. But in plants, it’s been very clear that certain epigenetic patterns can be transgenerationally inherited. For example, the Wisconsin cold can induce modifications of genes that can then be inherited. This is an area we are very interested in—environmentally induced epigenetic modifications and to what extent these modifications are transmitted to the next generation.

What plant do you use to study inherited epigenetics?

Currently we are primarily utilizing a flowering plant called Arabidopsis thaliana, or thale cress. It’s a model system that is widely used. We use it because it has a small genome, and because most of our studies are done at the whole genome scale, it’s cheaper than other model systems. Also, the generations are very short, only eight weeks. You can look at six generations in just a year. We’ve also started to extend our work to rice and maize through other collaborations on campus.

Can you explain what you’ve learned about plant aging in your work?

We have been finding that one epigenetic complex in particular is very important to make sure that a plant senesces, or ages, at the right time. Early senescence can reduce yields, so if we can find a way to delay senescence we can hopefully increase productivity. And that’s exactly what we see. If we get rid of the complex we’ve found, senescence is significantly delayed.

While we often talk about how delaying aging is good, the opposite can be true, too. Here in Wisconsin, we have relatively short windows for growing plants. If we can promote senescence, we can maybe shorten the plants’ growing season to better fit our weather patterns.

Now we are trying to understand the mechanism behind these changes because only when we know the mechanism can we really manipulate the system. Ideally, we will be able to manipulate things both ways by fine-tuning the epigenetics to different levels. It’s not all or nothing—it’s kind of an art.

How can your work help address concerns about climate change?

Heat and drought will make the areas that can grow plants limited and challenging in the future. This is a big motivation for us. We want to know what kind of epigenetic modifications happen in response to heat and drought—how strongly, uniformly, stably and rapidly do these modifications happen? Also, is this inheritable? If we treat a plant with heat and collect its seeds, will the next generation “remember” that past experience? Can that memory help the plant?

Why is it difficult to study the influence of environmental factors on epigenetics?

In the lab, it’s simple because we can control each factor and use one kind of stress. But in the real world, you are going to have multiple factors, and how they crosstalk is very complicated. Heat is associated with drought, and there may be long, dark nights and short days as well. I am interested in finding the epigenetic complexes responding to all of these factors. Ideally I want to combine all this information to establish an environmental epigenetic regulatory network. And if there is one key complex responding to all kinds of factors, that can be our target.

Is there a way to do very targeted epigenetic work?

One area we are getting into is epigenome editing (also named epigenome engineering) using a modified CRISPR–dCas9 system that others are using for genomic editing. This lets us target the genes involved in aging, let’s say, and then change only those few genes we have identified to be important. We can put a modification only in that place or on those genes. It’s more efficient.

Using CRISPR–dCas9, the epigenetic changes hopefully will be stable. That’s a question right now because we haven’t gotten to that step yet, but I hope that’s true. Ideally once we have the modification on there, it should stay and do its job.

How are epigenetic studies being used beyond the lab?

I am most interested in how epigenetics can be applied to horticulture and agriculture, but many people are interested in epigenetics for drug discovery. In human medicine, there is already a drug used clinically called azacitidine, which is used to treat a bone marrow disorder called myelodysplastic syndrome and works by blocking the methylation of DNA. This is still a huge, growing area, and whether lab findings can be used in the field or in practice is a million-dollar question. We need efforts to take the discovery from the lab into the field. Making that connection is important and challenging work in all areas of research.

Xuehua Zhong uses plants to study epigenetics, an exciting new field that is broadening our understanding of how some traits might be passed down from one generation to the next. Photo credit: Sevie Kenyon BS’80 MS’06

Lactation Sensation

WHEN THE CITY GIRL decides to study lactation, she must first learn to milk a cow. Laura Hernandez, an assistant professor of dairy science at CALS, remembers that lesson.

Her tutor that day was Jessica Cederquist, then a fellow grad student and now CALS herd manager. “People who have never milked are used to what you see in the movies,” Cederquist explains. You know the choreography: grab a teat, pull down, milk squirts into the bucket. But that technique simply squeezes milk back into the udder. And just about everybody makes the mistake. “It is a rite of passage to stand back and laugh,” she admits.

“She thought it was very funny,” Hernandez recalls. “I think that was the beginning of a very good friendship.”

The milking got a little crazier once Hernandez ramped up her inquiries into how lactation works. Her first experiments required milking two halves of the same cow, comparing milk production. Because she was pairing the front right with the back left and vice versa, she had to replumb two half milkers, using a surplus of hoses and buckets. She’d also recently had knee surgery.

“You’re already kind of crowded in there and now you’ve got her fancy contraption and all of her buckets and a big old knee brace,” says Cederquist. And it’s a waterbed stall, so every time anybody moves, the floor moves, and the buckets yaw precariously. “She’s darn near laying on the floor under the cow, trying to figure out how she’s going to get this thing to stay on.”

Hernandez is still making things unusual for Cederquist. Lactation is a delicate enough phenomenon that the typical dairy farmer puts animals who are in the late stages of pregnancy on vacation. This is exactly when Hernandez needs to poke and prod, monitor and manipulate.

The hassle seems worth the reward: Her exploration of the role of serotonin in lactation has the potential to significantly improve animal health and boost milk production. There may also be profound lessons about the role of serotonin in human health. While seratonin was once considered the miracle molecule of mental health, Hernandez is helping unravel its role in many more parts of the body.

“There is still an infinite box of things it probably does that we can’t understand,” says Hernandez. Which is all the more interesting because it’s such a simple molecule, just a modified amino acid. It’s as if a Lego block were able to control a nuclear reactor. “I really am just completely fascinated by how a modified amino acid can regulate what feels like the universe at times,” Hernandez says.

On the road between Hernandez’s hometown of El Paso, Texas, and the New Mexico State University campus in Las Cruces, a line of dairy farms stretches across the landscape. Despite her urban upbringing, the cows fascinated her. “As an athlete I was like: how does she do that?” recalls Hernandez, then a scholarship swimmer. “I just thought they were really cool animals, what they could do from a biological standpoint.”

Drawn to biology, Hernandez chose animal science over straight biology because she was more interested in working with mammals than with crabs and nematodes. But her real immersion didn’t begin until her senior year, when she transferred to New Mexico State from Iowa State University. In Ames her swimming schedule had kept her out of the lab, but that changed when she got to Las Cruces.

“I loved working in the lab,” says Hernandez. “That was where I found my home.” When she couldn’t decide between professional schools, she continued at New Mexico State to earn a master’s degree in animal science and toxicology.

In 2005 she started her doctorate at the University of Arizona with Bob Collier, a physiologist in the dairy sciences. He was interested in how genes interacted with the environment, and lactation was the ideal process to study: genetically programmed, but initiated and controlled by changes in the environment of the cow.

The year before Hernandez arrived, the small world of lactation science had been upended by the unexpected discovery that serotonin, long considered simply a neurotransmitter, also had a role in regulating lactation. Collier reached out to Nelson Horseman at the University of Cincinnati, where the discovery had been made. Horseman studied breast development, but his central interest was breast cancer. Collier offered his dairy expertise and suggested that they collaborate on expanding this discovery from the mouse to the cow.

Hernandez undertook the research for her dissertation, supervising many of the active experiments. Deeper she went, her work encompassing an intense collaboration into the complex molecular underpinnings of milk production.

After finishing her Ph.D. she began a postdoc in Horseman’s lab. One day in Cincinnati, Gerard Karsenty, a geneticist visiting from Columbia University, presented his research involving gut serotonin, calcium and bone mass. Afterward Hernandez turned to Horseman and wondered aloud: If gut serotonin had a role in bone mass, could this also help explain its role in lactation?

Nursing typically requires more calcium than diet alone can provide, and the difference comes from the mother’s bone. A nursing mouse will lose up to 20 percent of bone mass in 21 days. Human mothers can lose 6 to 10 percent of their bone mass over six months. Studies in West Africa and Korea suggest that the longer a woman breast-feeds, the lower her bone density.

It’s not surprising that serotonin might have more than one role in the body. Along with dopamine it’s the oldest known hormone, and nature loves to reuse its creations. In fact, serotonin first evolved in plants. Plants have no nervous system, so it couldn’t have been a neurotransmitter. How a simple molecule engages in complex processes is by acting as a molecular key in many different cellular locks. Scientists have now identified 20 different serotonin receptors. The mammary gland alone has five.

So how to uncover serotonin’s role in withdrawing calcium from bone? Scouring some old genetic assays, Hernandez found a likely ally: parathyroid hormone-related protein (or PTHrP). Her initial tests were so strong that she suspected her equipment was off.

But further experiments confirmed that serotonin was causing an increase in PTHrP in the mammary gland during lactation. This, in turn, was a key signal liberating calcium from bone for the mammary glands.

Hernandez’s research portfolio made her an obvious match when a position opened at CALS. As a newly hired professor in 2011, her first question was obvious: Could she leverage our knowledge of PTHrP in the dairy cow?

Lactation is hard, and one of the biggest problems faced by dairy farmers is the “transition cow,” a cow in the three weeks before and after calving. Between the physiologic stress of birth and the metabolic stress of commencing lactation, for the first 20 to 30 days of lactation the cow is expending more energy than she can take in.

Calcium complicates things, as it takes a couple of days to activate the mechanism that borrows from the bone. Sometimes that leads to a calcium deficit—or hypocalcemia, also knownas milk fever. Because calcium is critical for biological functions, assisting with everything from muscle contraction to immune function, a shortage can lead to a variety of potential health problems including ketosis, displaced abomasum and retained placenta. Gut issues can arise because the intestines aren’t contracting. Reduced immune function leaves the cows more susceptible to mastitis.

“That’s a precarious time frame for them,” Hernandez says. “If you have a calcium problem, other issues compound.”

It’s a daily concern for dairy farms. Even on a very good farm, 3 to 5 percent of the animals are going to wind up with milk fever. Scaled up to a 10,000-herd farm, that means one or two affected cows every day.

“Not every farmer is going to automatically relate to Hernandez’s deep molecular work,” says herd manager Jessica Cederquist. But put it in terms of milk fever and the transition cow, and “every dairy farmer on the planet knows what that means,” she says.

With startup money tight and a big idea, Hernandez developed an ambitious research agenda. She found a collaborator in Jimena Laporta, a graduate student fresh from Uruguay. Laporta read the plan and committed the very next day. “We were throwing all of the chips on the table and hoping for a win,” says Hernandez.

The idea was simple: Could you boost PTHrP levels with nutritional supplements? They fed rats two amino acids—5-hydroxytryptophan (abbreviated as 5-HTP) and straight tryptophan. Both are chemical precursors in the synthesis of serotonin.

They began with rats, and feeding was the easy part. The hard part? They also had to milk them. Forty-five rats. Every day. How do you milk a rat?

After knocking it out with sleeping gas, you inject a minute quantity of the hormone oxytocin. A small suction device evacuates the teats; each animal has 10. It was a time-consuming, two-person job. Hernandez and Laporta sacrificed weekends and postponed professional travel. Eventually they got the process down to about an hour and a half.

The 5-HTP worked. Then they confirmed that it works in the cow via IV infusion. Now the lab is working on developing a cow feed that accomplishes the same thing.

Meanwhile, on the molecular level they were focusing on how the serotonin was actually affecting the mammary gland and how it translated into the chemical signals that drive bone resorption. In addition to the PTHrP they identified a gene—already nicknamed sonic hedgehog—as another link in the chain in collaboration with researchers Chad Vezina and Robert Lipinski at the UW–Madison School of Veterinary Medicine.

“It’s a very big picture of a very small molecule,” says Laporta, now teaching at the University of Florida. “Nobody knew that serotonin could do all these things. I think we opened a black box.”

Repeat: lactation is hard. Hernandez became a mother in the first year of her professorship, and nursing was as fulfilling as it was excruciating. She was lactating, she was teaching about lactation, she was manipulating lactation. Under the grueling stress of a new research program she took only nine days of maternity leave.

One day in mid-February her husband came home to find Hernandez crying on the bathroom floor. She couldn’t find time to pump, and her hair was falling out. He suggested it might be time to stop nursing. She’d made it seven months under a colossal workload. They still had some milk stored to facilitate transition to the bottle. “But I want to make it a year,” Hernandez objected. “I’m a lactation biologist! I must!”

“It was so hard,” she reiterates. “It’s made me even more of an advocate for helping women after they give birth. That’s where my biggest interest is: The mother’s ability to deal with lactation and to do so healthily for herself while also taking care of her baby.”

And so Hernandez has forged into human health. As the role of serotonin beyond brain chemistry continues to unfold, obvious questions arise. Selective serotonin reuptake inhibitors, or SSRIs, now dominate the antidepressant market and include such household names as Prozac, Paxil and Zoloft. Among their side effects is a decrease in bone density. Nursing also decreases bone density. With 12 percent of pregnant women taking SSRIs, does the combination of SSRIs and nursing set these women up for severe bone health issues later in life?

Most studies that looked at nursing and SSRIs focused on the infant. “Almost nothing out there looks at the long-term implications for the mother,” reports Sam Weaver, a third-year Ph.D. student in Hernandez’s lab. Weaver began as an undergraduate in the lab, assisting Laporta with her milking. Now Weaver supervises her own mouse dairy as she tries to untangle the precise impact of SSRIs on lactation and the health of the mother.

Weaver harvests more than milk. The mice are dissected with precise determination as blood, mammary glands, kidneys, intestines and bone tissue are examined for health and their reactivity to serotonin. Their femur bones are sent off to a collaborator in Boston for specialized imaging.

“Can we somehow help women breast-feed but also stay on their medication, and help them avoid some of these long-term bone issues?” asks Hernandez. She hopes to begin working with human populations soon.

Now that the lab has characterized the complexity of serotonin in lactation, the team is trying to get a handle on its role as one of the body’s master regulators. Only about 2 percent of serotonin actually resides in the brain; the vast majority circulates throughout the rest of the body. “We’re finding it popping up in all sorts of places,” says Weaver.

A newer project is working on yet another serotonin-lactation connection. Obese women tend to have higher serotonin levels—and they also have a harder time initiating nursing. This suggests yet another crucial role for serotonin as a regulator of energy balance in the body. By unlocking its role, they hope to find a way to make nursing easier for these mothers.

The legacy of Wisconsin is so milk-soaked it can be hard to remember that lactation still holds mystery and marvel. It’s a unique biological process that has given up its secrets slowly, and there is still much to learn. Experiments with a wide variety of mammals have shown that as long as you keep removing milk, the gland will keep making it.

Though she’s unlocked some of the secrets behind this apparent superpower, Hernandez remains entranced: “It just fascinates me that it can continue to do that.”

It’s not a stretch to call lactation one of the more significant developments in the evolution of life on this planet. The expanded ability to feed our young has allowed mammals to adapt to a wide array of variations in our environment. “Keep the baby alive,” says Hernandez. “I think it ties back to that, making us better mothers.” Our human accomplishments are stamped with an indelible mammalian signature.

Hernandez’s peculiar dairy, with its few hundred mice and few dozen patient cows, keeps producing under the labors of a handful of motivated students. “Sometimes it’s overwhelming, and it feels like we’re not getting anywhere and we’re not going to get anywhere,” Hernandez says. “Because with every answer comes another question.”

Even as she continues her fine-scale investigations, Hernandez hopes that young farmers can go back to their dairies and incorporate some wonder into our conversations about animal agriculture.

As Hernandez and dairy farmers know, when it comes to a cow’s well-being, milk is a marker.

“If cows are not being fed properly, or taken care of properly or housed properly, they are not going to make a lot of milk,” Hernandez says. “That’s a basic mammalian response. That should tell you something about the welfare of the animals.”

Class Act: Timothy Guthrie

Biochemistry senior Timothy Guthrie knows that science and success are about small steps. It’s those tiny strides that drive him to excel both in the lab and in the pole-vaulting pit.

Last summer Guthrie, a student athlete, earned a summer Biochemistry Undergraduate Summer Research Scholarship and spent lots of time in the lab of biochemistry professor Judith Kimble. There he worked, and continues to work, on making different mutations in a protein important for stem cell renewal.

“When I finally get something right in the lab that I’ve been working on for a month or two, it’s a really satisfying feeling,” says Guthrie, who plans to apply to medical school this summer.

Guthrie’s work allows the lab to better understand the molecular mechanism behind stem cell renewal in a tiny roundworm species called Caenorhabditis elegans, used as a model because their stem cells are easier to study than those in humans. Stem cell renewal is essential for the organism to keep producing cells it needs to develop and reproduce. By making different mutations to a protein important to this process, researchers can work to determine the role of the protein.

“The ultimate goal of stem cells is for therapeutic use, but we’ve got to work to understand the stem cells first—and the only way to do that is piece by piece,” says Guthrie. “That’s what Professor Kimble’s lab is doing.”

Getting involved in undergraduate research has helped Guthrie gain critical lab experience and also helped build connections between what he learns about in class and the experiments he performs in the lab.

“Along with knowledge of lab techniques and research, I’ve gained a better appreciation for the scientific discoveries we’ve already made,” he says. “All of those big successes and drugs we’ve discovered were made up of small steps like the ones I get to be a part of in the lab.”

Timothy Guthrie, Biochemistry senior, works with data on stem cells research.
Photo by: Robin Davies/UW–Madison MediaLab at Biochemistry

Undergrad helps teach orphans about hydroponic farming

There are capstones, and there are capstones.

For his capstone—a discipline-spanning research project required of all students graduating from CALS—soil science student Jacob Kruse BS’16 spent a summer working with orphans in Lima, Peru, to set up and run a hydroponic growing system.

More than 60 children from the Casa Hogar Juan Pablo II orphanage—a mission of the Diocese of La Crosse, Wisconsin—participated in growing crops that included tomatoes, peppers, bok choy and lettuce. The kids learned all about hydroponics, the art of growing plants in water, sand or gravel instead of soil, adding nutrients as needed.

But the project’s overarching benefits ran deeper. Beyond producing and learning about healthy food, “The goals were to teach children about water and natural resource use and reuse, help build connections between families and friends through common interests and projects and help the children develop responsibility,” says Kruse.

Kruse spent three months helping build the system and offering hands-on instruction on the basics of hydroponics—one class for older children and another for the younger ones. The kids learned about the environmental benefits of hydroponics, how to build home hydroponics out of household items and how to care for the garden.

A manufacturer of specialty chemicals for construction and industry, Sika Peru S.A., funded the project and built the garden structures with recycled materials. Mantisee, a nonprofit organization, provided the system design and plants. Both organizations, Kruse says, are concerned with natural resource use and social development, and they see the hydroponic system as a way to teach water use and nutrient efficiency—an important point in Lima, the world’s second-driest capital city.

Sika has also set up a scholarship and internship program for children at Casa Hogar who complete the hydroponic classes. “Sika’s scholarship and internship program will truly be life-changing for our children, and this collaborative project will have a lasting impact on our orphanage and the children who call it home,” says Jordan Zoroufy, Casa Hogar’s director of development.

Kruse’s faculty advisor, soil science professor Phillip Barak, is both impressed and delighted with the project. “We like our capstone experiences to be very hands-on and to have a service component,” Barak says. “Jake’s self-designed capstone sets a very high bar—food, children and education. Helping build a hydroponic food system from the ground up and turning it over to the children in the orphanage is quite an accomplishment.”

Adventures in Global Health

When it comes to study abroad experiences, an elephant ride in Thailand is pretty hard to beat.

“The entire time we were around the elephants, I was smiling uncontrollably,” says Gilad Segal, a microbiology major. “It was amazing to interact with them and get a sense of their personalities. Riding on the back of an elephant through the jungle and into a watering hole is something I never imagined I would do.”

And it was a great way to learn about the animals and efforts to protect them. Located in the “Golden Triangle”—the fabled convergence of Thailand, Myanmar and Laos—the Anatara Elephant Sanctuary improves the health and well-being of elephants by renting them from their owners and then caring for the elephant, the owner and his family as they continue to work humanely with tourists. In that part of the world, elephants frequently are victims of exploitation in the tourist industry, where their owners, called “mahouts,” earn a living by offering rides and having elephants perform tricks, often while not receiving adequate care.

“This solution allows the mahout to still live comfortably in that the camp provides them with a place to live and a monthly stipend for their elephant,” explains fellow microbiology major Lauren Raasch. “The elephants are cared for and are not overworked for tourist purposes.”

The students also examined the elephants’ microbiota by swabbing various parts of the animals and isolating and identifying microorganisms back in the lab at Mae Fah Luang University in Chiang Rai, Thailand.

The elephant camp was only one of several excursions during the seven-week, five-credit study abroad experience. The combined Microbiology 304/ Languages and Culture of Asia 300 program was the brainchild of bacteriology instructor Jon Roll BS’88 PhD’96, who developed the idea with biology advisor Todd Courtenay and teamed with Anthony Irwin, a doctoral student in the Department of Asian Languages and Cultures, to lead the course’s cultural components.

The program debuted last summer with 14 students and is poised to reach its cap of 20 students in summer 2017. It satisfies a required field study component for the popular Undergraduate Certificate in Global Health, a CALS-administered program in UW–Madison’s Global Health Institute.

Roll got the idea when visiting Mae Fah Luang University to explore research collaborations. “I saw their instructional lab facilities and was very impressed,” he says.

The course kicks off with a week of cultural orientation at another institution, the International Sustainable Development Studies Institute in Chiang Mai. There students learn some basic Thai and become acquainted with various aspects of Thai culture, which include wearing uniforms to class (a white top and dark pants or skirts); not pointing at things (which is considered rude); taking shoes off when entering a home; eating dinner food for breakfast (the Western idea of breakfast food doesn’t exist); and, above all, keeping voices down. “Tone it down like 10 notches,” advises Raasch in a blog she kept on the trip, noting that the Thai communication style tends to be quieter and less confrontational.

In addition to the elephant camp, field trips included meeting with SOLD, a nonprofit that offers job training to young people at risk for sex trafficking, and learning about nutrition and food safety from a monk who is well known for his scholarship in those areas.

As for the basic science component, although Microbiology 304 is a demanding course, students appreciated the program’s hands-on, in-the-field approach to learning.

“The microbiology lab helped me learn a lot not only about microbiology, but also how science applies to everyday life,” says biology major Therese Renaud.

Students came home with a much bigger picture of the world.

“I just want to talk forever about everything I had the opportunity to experience,” says Raasch. “The cumulative experience of adapting to and gaining an appreciation of a new culture was by far the most memorable part.”

Catch up with . . . Jacquelynn Arbuckle BS’91 Genetics

Dr. Jacquelynn Arbuckle’s exposure to the medical field began when her younger brother Adrian was born with cystic fibrosis. Arbuckle, only six at the time, recalls a childhood consumed with Adrian’s care. “We spent many days and weeks at the children’s hospital. I watched the doctors and nurses carefully try to find ways to keep Adrian alive,” Arbuckle says. Each year he was expected to have only a limited time to live.

That experience led Arbuckle to dedicate her life to medicine. After graduating from the UW–Madison School of Medicine and Public Health (SMPH) and completing her surgical residency in Massachusetts, Arbuckle returned to Madison, where she is an associate professor and surgeon at UW.

Arbuckle’s path to success was not easy. A native of Spooner, Wis., and an Ojibwe, Arbuckle grew up on the St. Croix reservation. She experienced firsthand how difficult the transition from a reservation community to a college campus can be. Now, as director of the SMPH-based Native American Center for Health Professions, she encourages young people to enroll at UW–Madison. She hopes that, once trained, they can help strengthen communities that often lack medical infrastructure and other resources—the same resources that ultimately saved her brother’s life.

What are some difficulties you experience when recruiting young Native Americans?

Coming from a close, familiar environment to a large campus can leave a student feeling isolated. Our Native culture is part of everyday life, and it can be challenging to feel free to practice our Native teachings without fear of humiliation. The Native American Center for Health Professions attempts to provide a safe cultural home for students and a place for community by providing mentoring, support and guidance as well as opportunities to explore our Native cultures around the state.

Why is it important for more Native American students to enter the medical field?

We need more Native healers in our state and across our nation. We need to be able to provide improved health care in our home communities, and we need to provide good mentors and role models for our young people. Our reservations have limited funds and limited access to health care. We need providers at all levels of health, including public health researchers, nurses, doctors, physician assistants, physical therapists, social workers and pharmacists. At NACHP, we reach out to interested students around the state and encourage them to consider coming to UW for their education. We are able to provide rotations at tribal clinics for those who are interested in this experience. During the rotations, students are exposed to true patient-centered, coordinated care as well as a wealth of cultural experiences.

How do you maintain your connection to the St. Croix reservation?

Mainly through my family. I go home routinely and spend time there. I have made connections with our tribal health director as well as our education director, and we are working on ways to improve resources and motivate young people together.

Photo courtesy of University Communications

A New Weapon Against Bacterial Disease

Bacteria that are resistant to antibiotics are one of the biggest problems facing public health today. About 800,000 children worldwide die before their fifth birthday from diarrheal diseases that evade treatment. The concentration of those diseases is highest in parts of Africa and Asia.

To address the problem, CALS biochemist Srivatsan (“Vatsan”) Raman hopes to harness the power of phages—viruses that infect bacteria but leave humans unscathed. With help from a grant from the Bill and Melinda Gates Foundation, Raman’s team is designing phages to specifically target bacteria that are causing diseases in infants.

Raman describes antibiotics—how doctors usually fight infections—as hammers that take out many bacteria, both harmful and beneficial. This means they can affect the entire human microbiome, which is the community of microbes on, inside and around the human body.

“We do not yet have the tools to selectively edit the composition of a microbiome,” Raman explains. But that is one of the goals of his lab’s work with phages. Unlike antibiotics, phages are very specific. A phage only infects one type of bacterial host. It is this specificity that presents Raman and his researchers with opportunities—but also some challenges.

Phages, which resemble lunar landers, locate bacterial hosts by attaching to specific receptors on the cell’s surface. Once they have found their host, some phages, called obligate lytic phages, quickly infect the cell and replicate. Once replication is complete, the new phage progeny burst out of the cell, ready to infect and kill the next available host.

Raman’s goal is to be able to control many steps in this process. He is investigating a way to engineer a phage that can be programmed to target specific bacteria. By changing just the “legs” of the lunar lander, the designer phage can target and eliminate any bacteria the researchers wish.

However, while destruction of bacteria is the ultimate goal, the process also creates problems. Many bacteria contain toxins that are released if the bacteria die in large numbers. So Raman’s team is also trying to control the rate at which phages infect and kill cells inside the body. “We can keep the phage on a leash and determine when and where it can infect,” describes Kelly Schwartz, a postdoctoral fellow in Raman’s laboratory.

Raman believes “designer phages” have great promise for human health.

“I was drawn to this research because designer phages can provide a potential solution to the antibiotic resistance problem,” notes Raman. “These bacteria are resistant to anything you throw at them and are killers in developing countries.

“And the next question, if we are successful, is ‘How can we turn these phages into actual medications that can be delivered to these areas?’ That challenge awaits us further down the road,” Raman says.

Vatsan Raman in his lab: The biochemist is engineering viruses that can vanquish harmful bacteria. Photo by Robin Davies/UW–Madison MediaLab at Biochemistry

Growing Veggies with City Kids

Natalie Hogan, a sophomore majoring in dietetics and Spanish, hopes to practice nutrition education in schools, teaching kids about healthy foods. This past summer she honed her skills by gardening and cooking with school-age children in the Young Scientists Club, a program run by the Milwaukee-based Urban Ecology Center. Most of the kids were of Latino and African American backgrounds, and many live in neighborhoods where fresh produce is hard to come by.

In addition to preparing dishes like whole wheat pizza with fresh veggies—a big hit, Hogan says—kids took part in lessons about nutrition, sustainability and climate change, including such concepts as sustainable agriculture and carbon footprints from farm to table.

Hogan and her project partner, sophomore Katherine Piel, developed their curriculum through a Wisconsin Open Education Community Fellowship, an award totaling up to $6,000 offered by the Division of Continuing Studies and the Morgridge Center for Public Service.

Hogan learned as much from the children as they learned from her. The kids at the Urban Ecology Center’s Menomonee Valley branch were excited about gardening— planting, watering, harvesting and even weeding—while kids at Washington Park loved to cook. Hogan and Piel tailored lessons to suit those preferences, recognizing that enthusiasm is a key ingredient in learning.

The experience led Hogan to broaden her career goals. She still wants to teach children, but she’d like to include families and the larger community. “The parents are the ones buying the groceries and cooking the meals,” says Hogan. “In order to make a difference, I must work to make an impact on parents, educators, policy makers—on all those who play a role in the health of our planet and people.”

And she relished the small victories, like getting 8-year-old Victorio to eat a radish. Initially he made a “yuck” face, but out in the garden, after being the first to spot the red tops, he took charge of harvesting, washing, cutting and adding them to a salad.

“When it came time to eat them, he described them as ‘crunchy and spicy, but still pretty good!’” says Hogan. “That was a positive experience because we could see his change in attitude. And he wasn’t the only one!”

Five things everyone should know about . . . Pulses

1. You’ve eaten them without knowing it. If the word “pulse” as a food leaves you flummoxed, fear not. The word pulse comes from the Latin word “puls,” which means thick soup or potage. No doubt you’ve enjoyed dried beans, lentils and peas in a soup or stew. Pulses are the edible dried seeds of certain plants in the legume family. Soybeans, peanuts, fresh peas and fresh beans are legumes but not considered pulse crops. Some lesser-known pulses like adzuki bean and cowpea play critical roles in diets around the world. Many pulses are economically accessible and important contributors to food security.

2. They’re very nutritious. Pulses contain between 20 and 25 percent protein by weight—twice the amount you’ll find in quinoa and wheat—and next to no fat. Around the world, they are a key source of protein for people who don’t eat meat or who don’t have regular access to meat. Pulses need less water than other crops, which adds to their appeal and value in areas where water is scarce.

3. Pulse crops have other environmental benefits as well. As members of the legume family, pulses are capable of taking nitrogen from the air and putting it back in the soil in a form available to plants. This makes legumes a critical part of any crop rotation and contributes significantly to sustainable farming. Pulses are grown worldwide but are particularly well adapted to cool climates such as Canada and northern states in the U.S.

4. We’re learning a lot about pulses from a recently sequenced genome. Adzuki bean was domesticated 12,000 years ago in China and is one of the most important pulses grown in Asia. There it is known as the “weight loss bean” because of its low calorie and fat content and high levels of protein. A recent genome sequencing collaboration among scientists in India and China revealed that genes for fat were expressed in much higher levels in soybean than in adzuki bean, while genes for starch were expressed at greater levels in adzuki bean. Their findings suggest that humans selected for diversified legumes in their diet—some that would provide oil and others that would provide starch.

5. It’s their year! The 68th UN General Assembly declared 2016 the International Year of Pulses, so now is the time to eat and learn. Events taking place all around the world focus on everything from cooking pulses (sample recipes: fava bean puree, carrot and yellow split pea soup) to growing them and incorporating them into school lunches. Learn more at www.fao.org/pulses-2016/en/.

To Market, to Market

If you’re familiar with the College of Agricultural and Life Sciences (CALS), you no doubt know all about Stephen Babcock and his test that more than 100 years ago revolutionized the dairy industry by providing an inexpensive, easy way to determine the fat content of milk (thus preventing dishonest farmers from watering it down). What you might not know is that his great discovery went unpatented. The only money Babcock received for his invention was $5,000 as part of a Capper Award—given for distinguished service to agriculture—in 1930.

Just years before Babcock received that award, another entrepreneur was hard at work in his lab—and his discovery would break ground not only in science, but also in direct remuneration for the university.

In 1923, Harry Steenbock discovered that irradiating food increased its vitamin D content, thus treating rickets, a disease caused by vitamin D deficiency. After using $300 of his own money to patent his irradiation technique, Steenbock recognized the value of such patents to the university. He became influential in the formation in 1925 of the Wisconsin Alumni Research Foundation (WARF), a technology transfer office that patents UW–Madison innovations and returns the proceeds back to the university.

Discoveries have continued flowing from CALS, and WARF plays a vital role for researchers wanting to patent and license their ideas. But today’s innovators and entrepreneurs have some added help: a new program called Discovery to Product, or D2P for short.

Established in 2013, and co-funded by UW–Madison and WARF, D2P has two main goals: to bring ideas to market through the formation of startup companies, and to serve as an on-campus portal for entrepreneurs looking for help. Together, WARF and D2P form a solid support for researchers looking to move their ideas to market. That was the intent of then-UW provost Paul DeLuca and WARF managing director Carl Gulbrandsen in conceiving of the program.

“The idea of D2P is to make available a set of skills and expertise that was previously unavailable to coach people with entrepreneurial interests,” explains Leigh Cagan, WARF’s chief technology commercialization officer and a D2P board member. “There needed to be a function like that inside the university, and it would be hard for WARF to do that from the outside as a separate entity, which it is.”

D2P gained steam after its initial conception under former UW–Madison chancellor David Ward, and the arrival of Rebecca Blank as chancellor sealed the deal.

“Chancellor Blank, former secretary of the U.S. Department of Commerce, was interested in business and entrepreneurship. D2P really started to move forward when she was hired,” says Mark Cook, a CALS professor of animal sciences. Cook, who holds more than 40 patented technologies, launched the D2P plan and served as interim D2P director and board chair.

With the light green and operational funds from WARF and the University secured, D2P was on its way. But for the program to delve into one of its goals— helping entrepreneurs bring their ideas to market—additional funding was needed.

For that money, Cook and DeLuca put together a proposal for an economic development grant from the University of Wisconsin System. They were awarded $2.4 million, and the Igniter Fund was born. Because the grant was good only for two years, the search for projects to support with the new funds started right away.

By mid-2014, veteran entrepreneur John Biondi was on board as director, project proposals were coming in and D2P was in business. To date, 25 projects have gone through the Igniter program, which provides funding and guidance for projects at what Biondi calls the technical proof of concept stage. Much of the guidance comes from mentors-in-residence, experienced entrepreneurs that walk new innovators down the path to commercialization.

“For Igniter projects, they need to demonstrate that their innovation works, that they’re not just at an early idea stage,” explains Biondi. “Our commitment to those projects is to stay with them from initial engagement until one of three things happen: they become a startup company; they get licensed or we hand them over to WARF for licensing; or we determine this project might not be commercial after all.”

For projects that may not be destined for startup or that need some additional development before going to market, the collaboration between WARF and D2P becomes invaluable. WARF can patent and license discoveries that may not be a good fit for a startup company. They also provide money, called Accelerator funding, for projects that need some more proof of concept. Innovations that may not be ready for Igniter funds, but that are of potential interest to WARF, can apply for these funds to help them move through the earlier stages toward market.

“Some projects receive both Accelerator and Igniter funding,” says Cagan. “Some get funding from one and not the other. But we work together closely and the programs are being administered with a similar set of goals. We’re delighted by anything that helps grow entrepreneurial skills, companies and employment in this area.”

With support and funding from both WARF and D2P, entrepreneurship on campus is flourishing. While the first batch of Igniter funding has been allocated, Biondi is currently working to secure more funds for the future. In the meantime, he and others involved in the program make it clear that the other aspect of D2P—its mission to become a portal and resource for entrepreneurs on campus—is going strong.

“We want to be the go-to place where entrepreneurs come to ask questions on campus, the starting point for their quest down the entrepreneurial path,” says Biondi.

It’s a tall order, but it’s a goal that all those associated with D2P feel strongly about. Brian Fox, professor and chair of biochemistry at CALS and a D2P advisory board member, echoes Biondi’s thoughts.

“D2P was created to fill an important role on campus,” Fox says. “That is to serve as a hub, a knowledge base for all the types of entrepreneurship that might occur on campus and to provide expertise to help people think about moving from the lab to the market. That’s a key value of D2P.”

Over the past two years, D2P, in collaboration with WARF, has served as precisely that for the 25 Igniter projects and numerous other entrepreneurs looking for help, expertise and inspiration on their paths from innovation to market. The stories of these four CALS researchers serve to illustrate the program’s value.

Reducing Antibiotics in Food Animals

Animal sciences professor Mark Cook, in addition to helping establish D2P, has a long record of innovation and entrepreneurship. His latest endeavor, a product that has the potential to do away with antibiotics in animals used for food, could have huge implications for the animal industry. And as he explains it, the entire innovation was unintentional.

“It was kind of a mistake,” he says with a laugh. “We were trying to make an antibody”—a protein used by the immune system to neutralize pathogens—“that would cause gut inflammation in chickens and be a model for Crohn’s disease or inflammatory bowel disease.”

To do this, Cook’s team vaccinated hens so they would produce a particular antibody that could then be sprayed on feed of other chickens. That antibody is supposed to cause inflammation in the chickens that eat the food. The researchers’ model didn’t appear to work. Maybe they had to spark inflammation, give it a little push, they thought. So they infected the birds with a common protozoan disease called coccidia.

“Jordan Sand, who was doing this work, came to me with the results of that experiment and again said, ‘It didn’t work,’” explains Cook. “When I looked at the data, I saw it was just the opposite of what we expected. The antibody had protected the animals against coccidia, the main reason we feed antibiotics to poultry. We knew right away this was big.”

The possibilities of such an innovation—an antibiotic-free method for controlling disease—are huge as consumers demand antibiotic-free food and companies look for ways to accommodate those demands. With that potential in hand, things moved quickly for Cook and Sand. They filed patents through WARF, collaborated with faculty colleagues and conducted experiments to test other animals and determine the best treatment methods. More research was funded through the WARF Accelerator program, and it became clear that this technology could provide the basis for a startup company.

While Cook didn’t receive funds from D2P to bring the product to market, he and Sand used D2P’s consulting services throughout their work—and continue to do so. Between WARF funding and help from D2P, Cook says starting the current company, Ab E Discovery, has been dramatically different from his previous startup experiences.

“D2P is a game changer,” says Cook. “In other cases, there was no structure on campus to help. When you had a technology that wasn’t going to be licensed, you had to figure out where to get the money to start a company. There were no resources available, so you did what you could, through trial and error, and hoped. Now with WARF and D2P working together, there’s both technical de-risking and market de-risking.”

The combination of WARF and D2P has certainly paid off for Cook and Sand. They have a team and a CEO, and are now producing product. Interest in the product is immense, Cook says. He’d like to see the company grow and expand—and stay in Wisconsin.

“It’s been a dream of mine to make Wisconsin a centerpiece in this technology,” Cook says. “I’d like to see the structure strong here in Wisconsin, so that even when it’s taken over, it’ll be a Wisconsin company. That’s my hope.”

Better Corn for Biofuel

Corn is a common sight in Wisconsin and the upper Midwest, but it’s actually more of a tropical species. As the growing regions for corn move farther north, a corn hybrid has to flower and mature more quickly to produce crop within a shorter growing season. That flowering time is determined by the genetics of the corn hybrid.

Conversely, delayed flowering is beneficial for other uses of corn. For example, when flowering is delayed, corn can produce more biomass instead of food, and that biomass can then be used as raw material to make biofuel.

The genetics of different hybrids controls their flowering time and, therefore, how useful they are for given purposes or growing regions. Shawn Kaeppler, a professor of agronomy, is working to better understand those genes and how various hybrids can best fit a desired function. Much of his work is done in collaboration with fellow agronomy professor Natalia de Leon.

“We look across different populations and cross plants to produce progeny with different flowering times,” Kaeppler explains. “Then we use genetic mapping strategies to understand which genes are important for those traits.”

Throughout his work with plant genetics, Kaeppler has taken full advantage of resources for entreprenuers on campus. He has patents filed or pending, and he has also received Accelerator funds through WARF. For his project looking at the genetics behind flowering time, Kaeppler and graduate student Brett Burdo received Igniter funds from D2P as well. The Igniter program has proven invaluable for Kaeppler and Burdo as they try to place their innovation in the best position for success.

“I found the Igniter program very useful, to go through the process of understanding what it takes to get a product to market,” says Kaeppler. “It also includes funding for some of the steps in the research and for some of the time that’s spent. I can’t fund my graduate student off a federal grant to participate in something like this, so the Igniter funding allowed for correct portioning of funding.”

The end goal of Kaeppler’s project is to develop a transgenic plant as a research model and license the technology, not develop a startup company. His team is currently testing transgenic plants to work up a full package of information that interested companies would use to decide if they should license the technology. For Kaeppler, licensing is the best option since they can avoid trying to compete with big agricultural companies, and the technology will still get out to the market where it’s needed to create change.

“In this area of technology transfer, it is important not only to bring resources back to UW but also to participate in meeting the challenges the world is facing with increasing populations,” says Kaeppler. “Programs like D2P and WARF are critical at this point in time to see the potential of these discoveries realized.”

A Diet to Treat Disease

Around the world, about 60,000 people are estimated to have phenylketonuria, or PKU. Those with the inherited disorder are unable to process phenylalanine, a compound found in most foods. Treatment used to consist of a limited diet difficult to stomach. Then, about 13 years ago, nutritional sciences professor Denise Ney was approached to help improve that course of treatment.

Dietitians at UW–Madison’s Waisman Center wanted someone to research use of a protein isolated from cheese whey—called glycomacropeptide, or GMP—as a dietary option for people living with PKU. Ney took on the challenge, and with the help of a multidisciplinary team, a new diet composition for PKU patients was patented and licensed.

“Mine is not a typical story,” says Ney, who also serves as a D2P advisory board member. “Things happened quickly and I can’t tell you why, other than hard work, a good idea and the right group of people. We’ve had help from many people—including our statistician Murray Clayton, a professor of plant pathology and statistics, and the Center for Dairy Research—which helped with development of the foods and with sensory analysis.”

Being at the right place at the right time had a lot to do with her success thus far, Ney notes. “I’m not sure this could have happened many places in the world other than on this campus because we have all the needed components—the Waisman Center for care of patients with PKU, the Wisconsin Center for Dairy Research, the clinical research unit at University of Wisconsin Hospitals and Clinics, and faculty with expertise in nutritional sciences and food science,” she says.

Ney is currently wrapping up a major clinical trial of the food formulations, referred to as GMP medical foods, that she and her team developed. In addition to those efforts, the new diet has also shown surprising promise in two other, seemingly unrelated, areas: weight loss and osteoporosis prevention.

“My hypothesis, which has been borne out with the research, is that GMP will improve bone strength and help prevent fractures, which are complications of PKU,” explains Ney. “I have a comprehensive study where I do analysis of bone structure and biomechanical performance, and I also get information about body fat. I observed that all of the mice that were fed GMP, whether they had PKU or not, had less body fat and the bones were bigger and stronger.” Interestingly, the response was greater in female compared with male mice.

To support further research on this new aspect of the project, Ney received Accelerator funds from WARF for a second patent issued in 2015 titled “Use of GMP to Improve Women’s Health.” Ney and her team, including nutritional sciences professor Eric Yen, are excited about the possibilities of food products made with GMP that may help combat obesity and also promote bone health in women.

“There is a huge market for such products,” says Ney. “We go from a considerably small group of PKU patients who can benefit from this to a huge market of women if this pans out. It’s interesting, because I think I’m kind of an unexpected success, an illustration of the untapped potential we have here on campus.”

Fewer Antibiotics in Ethanol Plants

Bacteria and the antibiotics used to kill them can cause significant problems in everything from food sources to biofuel. In biofuel production plants, bacteria that produce lactic acid compete with the wanted microbes producing ethanol. At low levels, these bacteria decrease ethanol production. At high levels, they can produce so much lactic acid that it stops fermentation and ethanol production altogether.

The most obvious solution for stopping these lactic acid bacteria would be antibiotics. But as in other industries, antibiotics can cause problems. First, they can be expensive for ethanol producers to purchase and add to their workflow. The second issue is even more problematic.

“A by-product of the ethanol industry is feed,” explains James Steele, a professor of food science. “Most of the corn kernel goes toward ethanol and what remains goes to feed. And it’s excellent animal feed.”

But if antibiotics are introduced into the ethanol plant, that animal feed byproduct can’t truly be called antibioticfree. That’s a problem as more and more consumers demand antibiotic-free food sources. But Steele and his colleagues have a solution—a way to block the negative effects of lactic acid bacteria without adding antibiotics.

“We’ve taken the bacteria that produce lactic acid and re-engineered it to produce ethanol,” says Steele. “These new bacteria, then, compete with the lactic acid bacteria and increase ethanol production. Ethanol plants can avoid the use of antibiotics, eliminating that cost and increasing the value of their animal feed by-product.”

The bacteria that Steele and his team have genetically engineered can play an enormous role in reducing antibiotic use. But that benefit of their innovation didn’t immediately become their selling point. Rather, their marketing message was developed through help from D2P and the Igniter program.

“Learning through D2P completely changed how we position our product and how we interact with the industry,” says Steele. And through that work with D2P, Steele plans to later this year incorporate a company called Lactic Solutions. “D2P has helped us with the finance, the organization, the science, everything. Every aspect of starting a business has been dealt with.”

Steele and his collaborators are now working to refine their innovation and ideas for commercialization using Accelerator funds from WARF. Steele’s work, supported by both WARF and D2P, is a perfect example of how the entities are working together to successfully bring lab work to the market.

“There is no doubt in my mind that we would not be where we are today without D2P,” says Steele. “On top of that you add WARF, and the two together is what really makes it so special. There’s nothing else like it at other campuses.”

With such a strong partnership campaigning for and supporting entrepreneurship at UW–Madison, CALS’ strong history of innovation is poised to endure far into the future, continuing to bring innovations from campus to the world. And that is the embodiment of the Wisconsin Idea.

 

Safer Nanotech

Although so tiny they are invisible, it’s easy to see that nanomaterials are becoming a big thing. There are odor-fighting socks and antibacterial dishrags impregnated with silver nanoparticles. Nano-sized titanium dioxide can be found in a long list of food and consumer products, including salad dressing, cake frosting, toothpaste and sunscreen. The vibrantly colored screen of the Kindle Fire can be attributed to quantum dots, a.k.a. nano-scale crystals of semiconductors such as cadmium selenide. And the list goes on.

Nanomaterials are tiny by definition, measuring between 1 and 100 nanometers along one or more dimension. (By comparison, a human hair is approximately 100,000 nanometers in width.) At this scale, they possess unique physical and chemical properties that make them useful for a wide array of applications, including consumer products, environmental remediation and medicine. Yet there are many unanswered questions about their safety.

“We don’t know a lot about the toxicity of nanomaterials, and we have much to learn about the potential risks associated with the release of these materials into the environment,” says Joel Pedersen, Rothermel Bascom Professor of Soil Science at CALS.

Pedersen is part of a collaborative, multidisciplinary research team exploring these unknowns as part of the UW–Madison-based Center for Sustainable Nanotechnology, which was founded in 2012 with support from the National Science Foundation. Center scientists are working to understand how nanomaterials interact with living systems and the environment, with the practical goal of developing the insights needed to start creating nanomaterials that are designed to be more environmentally benign. This includes re-engineering them to make them safer, if needed.

With expertise in chemistry, biology and engineering, Pedersen is in charge of the Center’s efforts to develop laboratory models to assess the biological impacts of nanomaterials. While he has done some experiments in zebrafish, Pedersen’s work for the Center focuses on innovative, non-biological approaches, including creating “artificial cell surfaces” in the lab.

“Our intent is to get down to the molecular level,” Pedersen explains. “What are the rules that govern how these materials interact with biological systems? In particular, how do these particles interact with cell membranes?”

One way Pedersen’s group makes artificial cell surfaces is by depositing lipid vesicles on a special quartz crystal sensor until the vesicles spontaneously rupture and then fuse to form a lipid bilayer—the basic structure of a cell membrane—on the sensor’s surface.

When electricity is applied to the sensor, it causes the system to vibrate at a particular frequency. Next, Pedersen’s team applies nanomaterials to the artificial cell surface. The sensor can detect subtle changes in the frequency of the vibration, yielding clues about the interaction between the material and the membrane.

By combining the results of this approach with others, Pedersen is finding that some nanoparticles, by virtue of their unique physical and chemical properties, seem to be able to extract lipids from the cell surface.

“Our results are consistent with the idea that these nanoparticles are grabbing lipids out of the membrane and acquiring a lipid coating when they come in contact with a cell,” explains Pedersen.

This cell membrane-disrupting behavior is a concern for the health of humans and animals. And while Pedersen’s team hasn’t observed this behavior in models of bacterial cell surfaces, there are other, broader concerns about the impacts of nanomaterials on microbial communities in the environment.

“Eukaryotes are our main focus, but there is some concern that nanomaterials in the environment can alter microbial community compositions. At present, we don’t know to what extent such changes could be problematic,” says Pedersen.

The information gained from Pedersen’s research will help inform the work of other scientists in the Center for Sustainable Nanotechnology who focus on tweaking nanoparticles to make them safer.

“Ultimately, the goal is to redesign nanomaterials to minimize their adverse effects, or find better ways to embed them in materials so they aren’t released into the environment,” Pedersen says.