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

Give: A Fitting Tribute

The late James F. Crow—an outstanding scientist, statesman, public servant and teacher—would surely have been happy with the solution arrived at by his colleagues and friends: a professorship named in his honor to ensure that great work in genetics continues.

The James F. Crow Professorship in Genetics will be made available to attract a world-class scientist to join the faculty in genetics. Endowment earnings will be made available to support the recipient’s research.

The professor who bears the title will build on the legacy of a giant. Crow was a pioneer in genetics. He measured the consequences of mutations—essentially, mistakes in DNA—for humans and other organisms, and he invented models that explain the pattern of DNA differences between individuals.

Crow’s discoveries made many of today’s genetic technologies possible, including commercial services that use DNA to reveal personal genealogy, the criminal justice system’s application of DNA evidence, and public health models that reveal why some diseases are common and others are rare. His work helped establish the University of Wisconsin–Madison as an international leader in genetics.

“Legions of the world’s most renowned geneticists trekked to Madison to visit Jim and meet with the broader community of geneticists on campus,” says John Doebley, genetics professor and chair of the UW–Madison Laboratory of Genetics.

Crow, an active member of the Laboratory of Genetics from 1948 to 2012, seamlessly integrated research with outstanding teaching and a passion for public service. One of his greatest gifts was his enthusiasm and ability to clearly explain genetic concepts to a wide range of audiences. He spoke to people he met in the community with the same admiration and excitement with which he greeted his scientific colleagues.

The professorship will honor Crow’s legacy by ensuring the continuation of discoveries with high societal relevance, notes Doebley. “Jim’s interests spanned the entire range of the field of genetics, but with a penchant for honing in on the most interesting and fundamental questions. As such, we can best honor his memory by following his instincts in this regard.”

You can make a gift to the James F. Crow Professorship in Genetics fund at http://supportuw.org/giveto/CrowProfessorship or contact Kate Bahr at the UW Foundation (tel. 608-308-5120, kate.bahr@supportuw.org).

A fundraising event for the named professorship will be held on Friday, September 23, 1–9 p.m. More info available soon at http://www.genetics.wisc.edu/CrowProfessorship.htm.

A Jolt to the System

As a linebacker for the UW–Madison Badgers, Chris Borland made a name for himself as a hard-hitting tackler. His senior year, he was selected as a first-team All-American as well as the top linebacker and defensive player in the Big Ten Conference.

A third-round draft pick, Borland seemed destined for a headline career in the National Football League. But during a full-contact practice at the San Francisco 49ers summer training camp in August 2014, Borland got his “bell rung” by a 290-pound fullback during a routine exercise. Though Borland felt dazed, he played through—as he’d done dozens of times before.

Like many football players, Borland had endured his share of hard hits, including two diagnosed concussions. This particular hit, however, got him thinking seriously about the future, and about the negative effects that repeated collisions could have on his long-term physical and cognitive health. Even so, he went on to play a dynamite rookie year.

Then, after the season was over, Borland quit.

The announcement shocked the sports world. Borland was 24 years old and healthy, yet chose to walk away from a $2.3 million, four-year contract.

“I just honestly want to do what’s best for my health,” Borland explained on ESPN’s Outside the Lines. “From what I’ve researched and what I’ve experienced, I don’t think it’s worth the risk.”

With their repeated hits, football players—along with boxers—are at increased risk of developing chronic traumatic encephalopathy (CTE), a degenerative brain disease marked by memory loss, depression, suicidal thoughts, aggression and dementia. Of 91 brains donated to science by former NFL players, 87 have tested positive for CTE. It’s seen as a likely contributing factor to nine suicides by current and retired football players over the past decade.

Borland didn’t want to share that fate.

“To me, Chris Borland is a hero. He walked away before he made the big bucks and he was very explicit about why he quit—that it was not worth it to him,” says CALS genetics professor Barry Ganetzky, whose findings about the central nervous system in fruit flies are shedding light on what hard hits do to humans.

Ganetzky isn’t a sports guy, but he started paying attention to football-related brain injuries after the 2012 suicide of New England Patriots linebacker Junior Seau, intrigued by the biological processes driving this tragic phenomenon.

“I started wondering, what’s the link between a blow to the head and neurodegeneration 10 or 20 years down the line? When I started digging into the scientific literature, it became clear that we know very little,” says Ganetzky, who held the Steenbock Chair for Biological Sciences for 20 years. “And my usual response is, well, if we don’t understand something about the brain, then we should be studying it in flies.”

Fruit flies, officially known as Drosophila melanogaster, are a widely studied model organism, with a vast arsenal of genetic and molecular tools available to support that work. Flies reproduce rapidly and are easy to work with, enabling swift research progress. They are well suited for brain research because they have nerve cells, neural circuitry and a hard skull-like cuticle remarkably similar to our own, allowing scientists to conduct probing experiments that would be difficult in rodent models—and impossible in human subjects.

Fly models already exist to study Alzheimer’s, Parkinson’s and a number of other neurological diseases. Why not concussion? But there wasn’t a model available.

Then Ganetzky remembered work he’d done decades earlier.

“It occurred to me that I knew how to make flies have a concussion, and I had done it 40 years ago as a post-doc,” says Ganetzky. “I thought, ‘That’s it!’”

It was a simple thing: As a post-doctoral researcher at the California Institute of Technology, Ganetzky decided to see if any of his flies happened to be bang-sensitive mutants, flies that display seizures and paralysis after given a high-powered swirl on a vortex machine. But he didn’t have a vortex nearby, so he decided to just bang the vials against his hand.

“After a couple of sharp whacks, some of the flies were hanging out at the bottom of the vial, stunned. Others were on their backs, obviously knocked out. And after a few minutes, they all got up and started walking around again,” recalls Ganetzky.

He immediately knew the flies weren’t bang-sensitive—it’s an extremely rare mutation—but Seau’s death helped Ganetzky realize they had displayed symptoms “very similar in many respects to the empirical definition of a concussion.”

After developing and validating the new fly model, Ganetzky and UW genetics professor David Wassarman have been able to charge forward with brain injury research. The model has already been used to reveal key genes involved in the body’s response to brain injury. It’s also poised to help unlock medical applications, including a genetic test for high-risk individuals and an assortment of promising drugs and treatments.

In addition to helping athletes in contact sports, these advances will benefit the millions of Americans each year who experience traumatic brain injury due to falls, car accidents and violent assaults.

“At the most fundamental level, we just want to understand how traumatic brain injury works,” explains Ganetzky. “However, this is a major medical problem for which there are not many good—or any good—treatments or therapies or preventives, and so that is part of our motivation. If we can learn the genes and the molecules and the pathways, can we come up with interventions?”

Ganetzky was raised in a working-class neighborhood in Chicago by a candy salesman father and a homemaker mother. Growing up, he had an abundance of natural curiosity and asked a lot of tough questions—and often questioned the answers he received. While this trait caused him some problems as a youth, it came to serve him well in science.

At the University of Illinois in Chicago, he figured he’d become a chemist for the good career prospects. He ended up switching to the biological sciences, however, after a 10-week honors biology research experience in a Drosophila lab that expanded into a two-year project. From that point forward he stuck with flies, earning his doctoral degree at the University of Washington and then doing his post-doc work at Caltech.

In 1979, Ganetzky joined the University of Wisconsin–Madison, where he chose to focus his research program on exploring temperature-sensitive paralytic mutants, flies that behave normally at room temperature, but then start to tremble and twitch—or pass out—when things heat up. For each mutant he identified, he sought to uncover the faulty gene involved, and thus better understand how brain cells work.

Over the decades, this approach enabled Ganetzky’s team to discover a number of critical genes and molecular pathways involved in brain cell signaling, including those required for the release of neurotransmitters. That body of work established Ganetzky as one of the foremost leaders in neurogenetics. Some of his findings shed light on human genetic diseases and led to a test that’s now routinely used to assess the safety of new pharmaceutical drugs. For his contributions, Ganetzky was elected in 2006 to the National Academy of Sciences, the nation’s preeminent scientific society.

After Ganetzky’s “eureka moment” about fly concussions in spring 2012, he immediately reached out to colleague David Wassarman, a genetics professor in the UW–Madison School of Medicine and Public Health. Wassarman, who studies human neuronal disorders using fruit flies, had already been attending Ganetzky’s lab meetings for a few years after some of their research findings linking the innate immune response and neurodegeneration dovetailed.

“I did a demonstration of fruit fly concussion for David, and I remember his response very well,” says Ganetzky. “His jaw kind of dropped, and he said, ‘If you’re not going to study that, then I want to.’”

It was exactly the response that Ganetzky had been hoping for. With retirement looming on the horizon, Ganetzky needed a trusted and enthusiastic collaborator to help pursue the work—someone who would be willing to take on more and more as time went on. Wassarman was game.

“I wanted to put both feet in,” says Wassarman. “I said, ‘If we’re going to do it, let’s do it.’”

As a first order of business, Wassarman developed a tool capable of delivering a consistent “dose” of brain injury to flies. The result, known as the High-Impact Trauma (HIT) device, utilizes a metal spring to slam a vial of flies against a firm foam surface. In this setup, it’s important to note, the brain injury the flies experience is caused by the rapid acceleration and deacceleration of their bodies; it’s not necessarily about a direct hit to the head.

“Quite often, as with football players, it can happen because they are running fast and then meet an immovable object. The concussion is caused by a kind of whiplash, where the brain is ricocheting off the inside the skull, and that’s what’s causing the damage,” says Ganetzky. “That’s what we’re doing here with the flies.”

Ganetzky and Wassarman found that flies injured using the HIT device exhibit many of the classic symptoms of traumatic brain injury (TBI) seen in humans. As they reported in the Proceedings of the National Academies of Science in 2013, flies show temporary incapacitation and loss of coordination immediately after injury. Those that survive severe injury go on to develop long-term symptoms: activation of the innate immune response, neurodegeneration and early death.

These TBI flies have the potential to reveal much-needed insights—and medical interventions—for the millions of Americans who experience traumatic brain injury each year. According to the U.S. Centers for Disease Control and Prevention, TBIs cause around 2.5 million emergency room visits, 283,600 hospitalizations and 52,800 deaths each year. Top causes are falls, motor vehicle accidents, and blows or jolts to the head or body, including sports-related concussions. Bomb blasts can cause brain trauma in soldiers in combat zones. Across the country, as many as 6.5 million people are believed to be struggling with the consequences of TBI, and the total economic cost of this health issue is estimated to be $76 billion per year.

In a demonstration of the power of the TBI model, Rebeccah Katzenberger, a senior research specialist in Wassarman’s lab, subjected 179 genetically unique strains of flies to four strikes of the HIT device—meant to simulate a series of severe brain injuries—and then monitored them for death at 24 hours post-injury, a data point that serves as an easy-to-measure proxy for the various negative events unfolding inside the body.

The results revealed a huge diversity of responses, underscoring the fact that genotypes matter when it comes to TBI response. Some strains were particularly susceptible to death, losing as many as 57 percent of the flies in those first 24 hours, while others were much more resilient, losing just 7 percent. The team then identified the genes that possibly made a difference, publishing their findings in eLife in March 2015.

“Now we have these 100 genes, and scientists can start looking at them in more detail,” says Wassarman. “A lot of them are genes that had never really been implicated in traumatic brain injury before. I think this is going to be one of our big contributions.”

These findings, the researchers note, may help explain why people respond so differently to similar brain injury events, and may help lead to a genetic test to identify high-risk individuals.
“Once we understand those genetic links, we’ll be able to test people and tell them, ‘Look, you probably shouldn’t play football. You should play non-contact sports,’” explains Ganetzky.

After identifying the TBI genes, Ganetzky and Wassarman immediately noticed a handful of genes involved in tissue barrier regulation. Tissue barriers—such as the intestinal barrier and the blood-brain barrier—function as biological blockades keeping “bad” things out while allowing “good” things to pass through.

To explore the connection between brain injury and tissue barriers, the duo had Katzenberger conduct a simple, colorful experiment that involves adding bright blue dye to the flies’ food. Under normal conditions, when flies eat the blue-colored food, it stays in the gut, something that is readily observable through the fly exoskeleton. However, after exposure to brain injury—via the HIT device or by having their heads pinched with a forceps—they found that the dye leaks out of the gut and turns the entire body blue, a phenomenon called “smurfing” (after the blue Smurf cartoon characters).

Leaky tissue barriers have previously been observed in rodent models of brain injury as well as in human medical cases. “Somehow this injury to the brain is triggering a series of events that leads to the breakdown of the intestinal barrier,” notes Ganetzky. “So there’s some sort of cross-talk going on between the brain and the intestine, but we don’t fully understand it yet.”

Upon further exploration, Ganetzky and Wassarman were able to confirm that—along with the blue dye—glucose and bacteria were also crossing the intestinal barrier into the fly’s circulatory system, or hemolymph, after brain injury. Homing in on glucose, they found that it plays a causative role in fly death after TBI. “By simply withholding sugar, we were able to keep some of these flies alive, and by a substantial margin,” says Wassarman.

If the findings hold up in rodent models and in human trials, he notes, athletes may one day find themselves advised to avoid certain foods after experiencing concussion.

The bacteria that cross the intestinal barrier appear to be playing more of a long game. Ganetzky and Wassarman believe they are the culprits triggering the innate immune response observed in TBI flies. The innate immune response, also known as the inflammatory response, is the body’s natural reaction to microbial invasion and other stressors. If properly controlled—turned on and off at the right time—it protects the body. If left on, however, it can cause collateral damage throughout the body, including damaging brain cells.

“Here’s what we think is happening: Traumatic brain injury is causing increased intestinal permeability. That causes the bacteria to leak out, which turns on the innate immune response, and that is possibly leading to neurodegeneration down the line,” explains Wassarman.

Ganetzky and Wassarman are intrigued by a concept that is emerging from their work and related studies: that TBI accelerates aging. Some of the key physical outcomes of brain injury—problems with tissue barriers and increased inflammation—are also hallmarks of the natural aging process. More support for this idea came in summer 2015, with the release of a report describing signs of early aging in the brains of war veterans exposed to bomb blasts in Iraq and Afghanistan.

“Somehow a blow to the head is activating all of these pathways related to aging and speeding them all up. Biologically, I think that this is maybe one of the most fascinating things about the whole project,” says Ganetzky, noting that TBI flies are a great model for further exploration.

Even at this early stage, without fully understanding the basic scientific mechanisms involved, the model is already revealing some promising medical applications. As soon as Ganetzky and Wassarman realized that the inflammatory response might lead to neurodegeneration, a treatment suggested itself: Could a simple anti-inflammatory help? They tried giving TBI-injured flies some aspirin mixed in their food. It helped.

“Our studies show that there appears to be a window of time after brain injury when the flies are particularly susceptible to dying. And if we can prevent certain events from happening during this time, then we can prevent death,” says Wassarman. “That’s what we think aspirin is doing—by lowering the innate immune response.”

The next step is to look for drug candidates that work even better than aspirin. Ganetzky and Wassarman are in the process of screening a set of 2,400 compounds, and they’ve already found a handful of very promising ones that can now be tested in rodent models and, ultimately, in human clinical trials.

“It would be wonderful if someday it were possible to offer a simple intervention beyond surgery to help individuals who have suffered a severe traumatic brain injury,” says Wassarman.

There’s a lot left to learn, and Ganetzky and Wassarman are eager to pursue all that the model can tell them. With Ganetzky’s retirement set for early 2016, the work of securing the project’s first federal grant and conducting experiments will largely fall to Wassarman.

But Ganetzky won’t be out of the picture. He continues to keep up on brain injury medical cases and scientific discoveries, and is encouraged by the national conversation about sports and brain injuries that’s starting to gain traction—and by the NFL’s commitment to scientific research in this area.

Some of these advances can be attributed, in part, to Chris Borland, whose post-NFL journey has led him deeper into the world of sports-related brain injury. Borland has submitted to numerous brain scans to support research, and has also become a sought-after speaker, touring the country to raise awareness about the risks of concussion.

It’s that kind of dedication to public service on the part of Borland and many other athletes, along with the excitement of discovery, that’s keeping Ganetzky in the game. Despite his retirement, Ganetzky plans to keep a scaled-back version of his lab running for at least a few more years.

Forever Rising

To begin to understand the outsized potential and sheer weirdness of yeast, it helps to consider the genetics behind one of the world’s most successful and useful microorganisms. It also helps to consider lager.

Lager, or cold-brewed beer, is made possible by the union of two distinct species of yeast. About 500 years ago, these two species, Saccharomyces eubayanus and Saccharomyces cerevisiae, joined in a Bavarian cellar. They gave us a hybrid organism that today underpins an annual global market for lager estimated at one-quarter of a trillion dollars.

“We would not have lager if there hadn’t been a union equivalent to the marriage of humans and chickens,” notes Chris Todd Hittinger PhD’07, a CALS professor of genetics and a co-discoverer of S. eubayanus, the long-sought wild species of yeast that combined with the bread- and wine-making S. cerevisiae to form the beer. “That’s just one product brewed by one interspecies hybrid.”

Yeasts, of course, are central to many things that people depend on, and the widespread domestication in antiquity of S. cerevisiae is considered pivotal to the development of human societies. Bread and wine, in addition to beer, are the obvious fruits of taming the onecelled fungi that give us life’s basics. But various strains and species of yeasts also are partly responsible for cheese, yogurt, sausage, sauerkraut, kimchi, whiskey, cider, sake, soy sauce and a host of other fermented foods and beverages.

Baker’s yeast, according to yeast biologist Michael Culbertson, an emeritus professor and former chair of UW– Madison’s Laboratory of Genetics, ranks as “one of the most important organisms in human history. Leavened bread came from yeast 5,000 years ago.”

Beyond the table, the microbes and their power to ferment have wide-ranging applications, including in agriculture for biocontrol and remediation, as well as for animal feed and fodder. They are also widely used to make industrial biochemicals such as enzymes, flavors and pigments.

What’s more, yeasts are used to degrade chemical pollutants and are employed in various stages of drug discovery and production. Human insulin, for instance, is made with yeast. By inserting the human gene responsible for producing insulin into yeast, the human variant of the hormone is pumped out in quantity, supplanting the less effective bovine form of insulin used previously.

Transforming corn and other feedstocks, such as woody plant matter and agricultural waste, to the biofuel ethanol requires yeast. Hittinger is exploring the application of yeast to that problem through the prism of the Great Lakes Bioenergy Research Center (GLBRC), a Department of Energy-funded partnership between UW–Madison and Michigan State University. Hittinger leads a GLBRC “Yeast BiodesignTeam,” which is probing biofuel applications for interspecies hybrids as well as genome engineering approaches to refine biofuel production using yeasts.

“There are lots and lots of different kinds of yeasts,” explains Hittinger. “Yeasts and fungi have been around since Precambrian time—hundreds of millions of years, for certain. We encounter them every day. They’re all around us and even inside us. They inhabit every continent, including Antarctica. Yeasts fill scores of ecological niches.”

The wild lager beer parent, S. eubayanus, for example, was found after a worldwide search in the sugarrich environment of Patagonian beech trees—or, more specifically, in growths, called “galls,” bulging from them. (How S. eubayanus got to Bavaria hundreds of years ago and made the lager hybrid possible remains a mystery.) It is possible, notes Hittinger, to actually smell the S. eubayanus yeast at work, churning alcohol from the sugars in the galls themselves.

Though the merits of known yeast species for making food, medicines and useful biochemicals are numerous, there are likely many more valuable applications of existing and yet-to-bediscovered yeasts.

For Hittinger and the community of yeast biologists at UW–Madison and beyond, a critical use is in basic scientific discovery. The use of yeast as a research organism was pioneered by Louis Pasteur himself, and much of what we know about biochemical metabolism was first studied in yeasts.

Since the 1970s, the simple baker’s variety of yeast has served as a staple of biology. Because yeasts, like humans and other animals, are eukaryotes— organisms composed of cells with a complex inner architecture, including a nucleus—and because of the ease, speed and precision with which they can be studied and manipulated in the lab, they have contributed significantly to our understanding of the fundamentals of life. And because nature is parsimonious, conserving across organisms and time useful traits encoded as genes, the discoveries made using yeast can often be extended to higher animals, including humans.

“The model yeast, S. cerevisiae, has been instrumental in basic biology,” says Hittinger. “It has told us something aging. In terms of understanding basic processes, it’s a tough model system to beat. It’s a champion model organism for genetics and biochemistry.”

“It is widely unappreciated how thevast terrain of biology has been nourished by yeast,” argues Sean B. Carroll, a CALS professor of genetics and one of the world’s leading evolutionary thinkers. It was in Carroll’s lab a decade ago as a graduate student that Hittinger first turned his attention to yeast, coauthoring a series of high-profile papers that, among other things, used the yeast model to catch nature in the act of natural selection, the proof in the pudding of evolutionary science.

Now the model is about to shift into an even higher gear. The work of Hittinger and others is poised toenhance the yeast model, add many new species to the research mix, and begin to make sense of the evolutionary history of a spectacularly successful and ubiquitous organism. The advent of cheap and fast genomics—the ability to sequence and read the DNA base pairs that make up the genes and genomes of yeasts and all other living organisms—along with the tools of molecular biology and bioinformatics promise a fundamental new understanding and order for yeast biology.

“This is all about weaponry,” explains Carroll, noting that Hittinger, in addition to possessing “great benchtop savvy and skill,” has armed himself remarkably well to exploit yeast genetics through the mutually beneficial prisms of molecular biology, evolutionary biology and bioinformatics (which harnesses computers to help make sense of the bumper harvests of data). “He has a determination and resolve to get the answer to any important question— whatever it takes,” says Carroll.

The big questions on the table for Hittinger and others include ferreting out “the genetic factors that drive species diversification and generate biodiversity,” and weaving that granular understanding into the larger fabric of biology. Because the functional qualities of all the various yeast species differ in order for the microbe to thrive in the many different environments it inhabits, the genetic code that underpins their different physiological and metabolic features varies accordingly.

In short, it takes a diversity of talents to inhabit every major terrestrial and aquatic environment the world has to offer. Species that thrive in South American tree galls and species that eke out a living on human skin require different skill sets in order to cope with vastly different environments and utilize different resources. Each of those skills is determined by the organism’s genetic makeup, and as scientists discover and extract the lode of genomic data found in new species discovered in the wild, new and potentially useful genetic information and metabolic qualities will come to light.

These are big, basic biological questions. But their answers promise far more than simply satisfying scientific curiosity. Yeasts are big business. They are medically and industrially important. The secrets they give up will, without a doubt, amplify our ability to produce food, medicine and industrial biochemicals.

To lay the groundwork, Hittinger and an international collaboration of yeast biologists are setting out, with support from the National Science Foundation (NSF), to map the genetic basis of metabolic diversity by sequencing the genomes of the 1,000 or so known species of yeast in the subphylum that includes Saccharomyces. Three hundred times smaller than the human genome, a typical yeast genome consists of 16 linear chromosomes and, roughly, 6,000 genes and 12 million letters of DNA.

“This is the best possible time to be a yeast biologist,” avers Hittinger. “Our collections have been vastly improved, and we can sequence genomes a hundred at a time. The important thing to know is that yeast is not just one organism or one species. There are thousands of yeasts, and they each have their own evolutionary history.”

Acquiring new species from the wild and sequencing their genomes will enable Hittinger and his colleagues to construct an accurate yeast family tree.

“If we don’t understand what’s out there and how they evolved, we’re notgoing to understand how to make use of them,” Hittinger notes. “Now, we can rip ’em open, get a peek at their genomes and see what the differences are and how they’ve changed over time.”

Thus stalking new strains and species of yeast in the wild is an essential part of the program, according to Hittinger, who routinely dispatches students, including undergraduates, to seek out new yeasts in nature. Half of all the known species of yeast have been described scientifically only within the past 15 years, meaning scientists have only a limited understanding of the world’s yeast diversity.

“Until recently, most strain collections have been paltry and biased towards domesticated strains,” says Hittinger. “If we can expand our understanding of the wild relatives, we can use them as an evolutionary model.Yeasts have a much less welldeveloped history in ecology and natural history.”

A recent yeast hunting excursion in Wisconsin by one of Hittinger’s students yielded three strains of the same S. eubayanus lager yeast parent found in tree galls in South America. Discovered near Sheboygan, the yeast has been cultured in Hittinger’s lab and samples have been provided to CALS food science professor James Steele, whose group is setting up a new comprehensive program in fermentation science and, with the help of a gift from Miller-Coors, a new pilot brewery lab in Babcock Hall. (Steele is also looking to support other fermented beverages in Wisconsin—namely, wine and cider— in both production and education. See sidebar on page 20.)

“We grew up a few hundred billion cells, gave them to Jim Steele to brew beer, and we’re eagerly awaiting the results,” says Hittinger, who explains that another focus of his lab is making interspecies hybrids, such as the lager hybrid. “Now that we’ve identified the wild species, we can make crosses in the lab to make hybrids that produce flavors people are interested in.”

In the food science realm, says Steele, yeast research is focused on the functional characteristics—fermentation qualities, sugar utilization, flavors—of a particular strain of yeast. “How does microbial physiology link to flavor in fermented beverages?” he asks.

Saccharomyces strains are the workhorse and best-known yeasts, including many of the most medically and biotechnologically important. With the $2 million award from NSF,
Hittinger and his colleagues will use the genomes to develop a robust taxonomy of important yeasts and look for the genetic footprints that give rise to yeast biodiversity, an  evolutionary history of their metabolic, ecological and pathogenic qualities. Such an understanding will elevate yeast to a new plane as a model and will undoubtedly serve as the basis of valuable new technologies.

Hittinger cautions, however, that sequencing yeast genomes is only a start: “We can very easily read gene sequences, but we don’t yet know how to interpret them fully. We will need to read those bases and make functional predictions” to extend both the knowledge of yeast biology and their potential use in industry.

“But if it weren’t for that natural diversity, we wouldn’t be able to enjoy Belgian beers,” says Hittinger, referencing the gifts conferred by different yeasts and their varied genetic underpinnings, resulting in the different flavors of ales, lagers and Belgians.

One of the central metabolic qualities of the familiar yeasts, of course, is their ability to ferment. Put simply, fermentation is a process by which cells partially oxidize or burn sugar. Among yeasts, the propensity to ferment in the presence of oxygen has evolved only in Saccharomyces species and a few others.

“To make a living using this process, you have to be a glucose hog,” says Hittinger. “But you don’t burn it all the way. You leave some energy on the table. Ethanol burns because it is unoxidized fuel.”

Different kinds of cells can perform fermentation if they become oxygenstarved Human cells, for example, ferment when starved of oxygen, causing painful muscle cramps. Given enough sugar, cancer cells can ferment, and do so to survive in oxygen-poor environments.

Indeed, Hittinger’s research on the cellular resemblance between Saccharomyces yeasts and cancer cells (for which he recently was named a Pew Biomedical Scholar) focuses on identifying which steps in yeast evolution were key to making the transition from respiratory to fermentative metabolic activity, as well as the sequence of those evolutionary events.

“Armed with that information, we should be able to shed some light on how cancer cells make that same transition over an individual’s lifetime,” says Hittinger.

Genes, Hittinger knows, hold the secrets to the functional qualities of yeast. Those microbial secrets, in turn, promise us food, fuel, pharmaceuticals— and, of course, beer. Like bread and wine, the gift of lager is no small thing. Who knows what other gifts, large and small, may lurk in the genes of these microorganisms?


Headed into the wild? If so, you could help Chris Todd Hittinger’s team identify new yeast species and strains. To learn more, visit http://go.wisc.edu/wildyeast

To watch an interview with Chris Todd Hittinger, visit http://go.wisc.edu/hittingerinterview


Brewing Beer-6005

Food science professor James Steele (left) and students are creating a red lager to be brewed by the Wisconsin Brewing Company. Steele and colleagues are launching a fermented foods and beverages program to take research and teaching to the next level.

“Farm to Glass” and More: Fermenting a Growth Industry

We all know Wisconsin as the land of beer and cheese. But in the not too distant future, Wisconsin may also become famous for other fermented products, notably wine and cider, thanks to growing public taste for those products and a blossoming wine- and cider-making culture in the Badger State.

Wisconsin now has about 110 wineries—up from 13 in 2000—and has been adding around a dozen new ones each year in recent years. Many of these operations could use some help, which is on the way in the form of a newly appointed CALS-based outreach specialist whose job is to support the state’s wine and hard apple cider industry.

Leaders of the Wisconsin Grape Growers Association, the Wisconsin Vintners Association and the Wisconsin Winery Association worked with CALS faculty in food science and horticulture to apply for a Specialty Crop Block Grant to support the position through the Wisconsin Department of Agriculture, Trade and Consumer Protection, with the associations providing matching funds. The specialist is scheduled to start working in early 2015.

The position is part of a larger effort to boost fermentation in Wisconsin. CALS food science professor James Steele and his colleagues are laying the groundwork for a comprehensive fermented foods and beverages program through the Department of Food Science—a program that will take to the next level much of the research and teaching the department has been building on for decades.

Already the program is bearing fruit—or, one might more literally say, “bearing beer.” Over the spring 2015 semester, students participating in Steele’s Fermented Foods & Beverages Laboratory will create and develop a new red lager recipe to be brewed by the Wisconsin Brewing Company and sold at the Memorial Union.

A central goal of the program, Steele explains, is to help improve the quality of fermented food and beverage products. As such, the functional roles played by yeast to influence such characteristics as flavor, color and other attributes will be very much in the spotlight.

“Yeast is a key player, beyond the shadow of a doubt,” says Steele. “It is extremely important, but from a food science perspective, it hasn’t gotten a lot of attention.”

With the help of yeast researchers such as Chris Todd Hittinger and his genetics colleague Audrey Gasch, Steele hopes to create an environment where the food science nuances of fermentation are teased out to the benefit of both growers and the producers of fermented foods and beverages.

The basic fermentation characteristics of various yeast strains are of interest, according to Steele: “For example, how does microbial physiology link to flavor in fermented beverages? These collaborations give us opportunities to look for new strains or develop new strains that could allow for the production of beverages with different flavors. And what we learn in one industry, we can apply to another.”

Made for the Shade

With the global population expected to reach 9 billion by 2050, the world’s farmers are going to need to produce a lot more food—but without using much more farmland, as the vast majority of the world’s arable land is already being used for agriculture.

One possible solution is to try to grow crops more densely in the field, thereby increasing yield per acre. But it’s not as easy as just spacing seeds more closely together at planting time.

Packed too tight, for instance, corn plants will grow tall and spindly as they try to outcompete neighboring plants for access to sunlight—a phenomenon known as shade avoidance.

“The problem with shade avoidance when it comes to food crops is that the plants are spending all this time and energy making stems so they can grow tall instead of making food that we eat,” explains CALS plant geneticist Richard Vierstra, who is developing a way around it. His team is reengineering a light-sensing molecule found in plants, known as phytochrome, to allow plants to grow normally even when they’re packed in tight.

“Instead of 30-inch rows, this technology could enable us to plant corn in 20-inch rows, boosting yields by as much as 50 percent—if we can get the plants to ignore their neighbors,” says Vierstra.

Phytochrome is the main photoreceptor that allows plants to tell when the lights are on and when they’re off. It’s what tells seeds to germinate and young seedlings to become green, and enables plants to establish circadian rhythms—an internal clock system, says Vierstra. “And it also allows a plant to sense whether it’s in full sun or whether it’s being shaded by other plants.”

In the lab, Vierstra and his team developed the first three-dimensional structures of phytochromes. Using these models, they are now trying to rationally redesign the photoreceptor to have altered light-sensing properties. This reengineering involves creating hundreds of possibly interesting phytochrome mutants, and then testing them for light sensitivity both in the test tube and inside plants.

Already Vierstra’s team has found a number of mutants that are extremely sensitive to light. These mutant phytochrome molecules, if genetically engineered into food crops, could trick the plants into thinking they are getting plenty of light, even when they’re growing in a crowded field.

Vierstra is in the process of patenting the technology and already knows of a large agribusiness company that’s eager to help commercialize it.

“We’re starting to engineer the phytochrome system in corn, in lines that will eventually be used for breeding,” he says. “It’s exciting to think about the potential this technology has to boost agricultural productivity.”

Microbes & Human Health

Jim Steele used to be one of the skeptics. He’d be at a conference, listening to early research on the health benefits of probiotics. Steele scoffed at the small experiments. “We would literally try not to laugh in the audience, but we’d laugh pretty hard when we went out that night,” he admits.

But slowly the punch lines gave way to revelation. Steele, a professor in CALS’ Department of Food Science, conducts research on lactic acid bacteria, with a focus on Lactobacillus species. They’re important for human gut health, critical for the production of cheese and yogurts, and are the most common probiotic genus. He knew how incredibly useful they were, but still watched with a humbling disbelief as the data on the health potential of these microbes kept getting broader, deeper and more intriguing.

Our microbiota—what we call the totality of our bacterial companions—is ridiculously complex. Each human harbors a wildly diverse ecosystem of bacteria, both in the gut and elsewhere on the body. They have us completely outnumbered: where the typical body may contain a trillion human cells, your microbial complement is 10 trillion. They have 100 times more genes than you, a catalog of life potential called the microbiome. (The terms “microbiome” and “microbiota” are often used interchangeably in the popular press.)

While our initial, germaphobic impulse may be to freak out, most of these bacterial companions are friendly, even essential. On the most basic level they aid digestion. But they also train our immune system, regulate metabolism, and manufacture vital substances such as neurotransmitters. All of these things happen primarily in the gut. “In many ways the gut microbiota functions like an organ,” says Steele. “It’s extraordinarily important for human health,” with as much as 30 percent of the small molecules in the blood being of microbial origin.

Early research has suggested possible microbiota links to protecting against gastric cancers, asthma, numerous GI disorders, autoimmune disease, metabolic syndrome, depression and anxiety. And the pace of discovery seems to be accelerating; these headlines broke in just a few months last spring:
• Mouse studies suggested that the microbe Akkersmania muciniphila may be a critical factor in obesity;
• Kwashiorkor, a form of severe malnutrition that causes distended bellies in children, was linked to a stagnant microbiota;
• Risk of developing Type 2 diabetes was linked to an altered gut microbiota.

The catch: For all the alluring promise of microbes for human health—and it’s now clear they’re critically important—we have almost no idea how this complex system works.

The human gastrointestinal (GI) tract is a classic black box containing hundreds or thousands of species of bacteria (how many depends on how you define a species). There are viruses, fungi and protozoans. Add to that each person’s distinct DNA and their unique geographic, dietary and medical history—each of which can have short- and long-term effects on microbiota. This on-board ecosystem is as unique as your DNA.

Beyond these singularities, the action is microscopic and often molecular, and even depends on location in the GI tract. Most microbiota studies are done with fecal material. “Is that very informative of what’s going on in the ileum?” asks Steele, referring to the final section of the small intestine, which is thought to be the primary site where immunomodulation occurs. “From an ecosystem perspective, fecal material is many miles away from the ileum. Is it really reflective of the ileum community?”

Making It Personal

It was one of the strangest homework assignments Erin Syverson had ever had. The senior genetics major was asked to open a small vial and start spitting.

“I would much rather have gotten my blood drawn, but it’s a simple, effective way to collect DNA at home without a medical professional,” notes Syverson, who submitted her saliva to 23andMe, a private company that analyzes a person’s DNA—all 23 pairs of chromosomes, hence the name—for $99.

Syverson underwent the analysis as part of Genetics 677, Genomic and Proteomic Analysis. While DNA testing is not required for the course, professor Ahna Skop encourages her students to undergo it. Students may use their own results as the basis of their individual semester-long class project, which requires doing in-depth research about a particular genetic disease or disorder and presenting findings in class and on a website the student creates.

“Because they have a vested interest in their project, they are emotionally engaged and seek out answers from me, their classmates and beyond the classroom—for example, from doctors and their families,” says Skop. “The payoff I see in my course is deeper, longer-lasting learning due to this emotional investment.”

Those benefits are being cited all around the nation as more and more college genetics courses encourage students to get tested. They were confirmed by a recent study in the journal PLOS One showing that 70 percent of students who underwent personal genome testing self-reported a better understanding of human genetics on the basis of having undergone testing. They also demonstrated an average 31 percent increase in pre- to post-course scores on knowledge questions, which was significantly higher than students who did not undergo testing.

Syverson didn’t end up basing her research project on her own results, but she still found the testing worthwhile. “Through learning to interpret my own results and scrutinize them, I have learned a lot about not only the diseases they tested me for, but also how to think critically about genetic results,” she says. “I’ve also learned a lot about the state of the field and how to explain it to others, which will be very helpful for my future career as a genetic counselor.”

The course will be offered again next spring. Student presentations are posted at
http://gen677.weebly.com/projects.html.

The Value of GMOs

For all the discussion surrounding genetically modified foods, there have been strikingly few comprehensive studies that put a numeric value on the costs and benefits.

Now there’s more to talk about.

By analyzing two decades’ worth of corn yield data from Wisconsin, a team of CALS researchers has quantified the impact that various popular transgenes have on grain yield and production risk compared to conventional corn. Their analysis, published in Nature Biotechnology, confirms the general understanding that the major benefit of genetically modified (GM) corn doesn’t come from increasing yields in average or good years—but from reducing losses during bad ones.

“For the first time we have an estimate of what genetically modified hybrids mean as far as value for the farmer,” says CALS and UW-Extension corn agronomist Joe Lauer, who led the study.

Lauer has been gathering corn yield and other data for the past 20 years as part of the Wisconsin Corn Hybrid Performance Trials, a project he directs. Each year his team tests about 500 different hybrid corn varieties at more than a dozen sites around the state, with the goal of providing unbiased performance comparisons of hybrid seed corn for the state’s farmers. When GM hybrids became available in 1996, Lauer started including them in the trials.

“It’s a long-term data set that documents one of the most dramatic revolutions in agriculture—the introduction of transgenic crops,” says Lauer, who collaborated with CALS agricultural economists Guanming Shi and Jean-Paul Chavas to conduct the statistical analysis, which considered grain yield and production risk separately.

Grain yield varied quite a bit among GM hybrids. While most transgenes boosted yields, a few significantly reduced production. At the positive end of the spectrum was the Bt for European corn borer (ECB) trait. Yield data from all of the ECB hybrids grown in the trials over the years showed that ECB plants out-yielded conventional hybrids by an average of more than six bushels per acre per year. On the other hand, grain yields from hybrids with the Bt for corn rootworm (CRW) transgene trailed those of regular hybrids by a whopping 12 bushels per acre. But even among poor-performing groups of GM corn, there are individual varieties that perform quite well, Lauer notes.

Where transgenic corn clearly excels is in reducing production risk. The researchers found that every GM trait package—whether single gene or stacked genes—helped lower variability. For farmers, lower variability means lower risk, as it gives them more certainty about the yield levels they can expect.

Lauer equates choosing GM crops with purchasing solid-performing, low-risk stocks. Just as safe stocks have relatively low volatility, yields from GM crops don’t swing as wildly from year to year, and most important, their downswings aren’t as deep.

GM crops help reduce downside risk by reducing losses in the event of disease, pests or drought. Economists Shi and Chavas estimated the risk reduction provided by modified corn to be equivalent to a yield increase ranging from 0.8 to 4.2 bushels per acre, depending on the variety.

Risk reduction associated with GM corn can add up to significant savings for farmers—as much as $50,000 for 1,000 acres, calculates Lauer. “It depends on the price that farmers can receive for corn,” he says.

But the two factors quantified in this study—yield and production risk—are just part of the overall picture about GM crops, says Lauer. He notes there are other quantifiable values, such as reduced pesticide use, as well as ongoing concerns about the safety and health of growing and eating genetically modified foods.

“There’s a lot of concern about this biotechnology and how it’s going to work down the road,” says Lauer, “yet farmers have embraced it and adopted it here in the U.S. because it reduces risk and the yield increases have been as good as—or some would argue a little better than—what we’ve seen with regular hybrid corn.”

Getting to the heart of a problem

When Marion Greaser set out to study titin, the largest natural protein known to man, his goal was to answer some basic questions about its role in the body. A major protein of skeletal muscle that’s also found in heart tissue, titin gives muscle its elasticity and is known for its massive size, which ranges from around 27,000 to 33,000 amino acid residues in length.

“Initially we were just going to look at whether titin was related to muscle growth in animals,” says Greaser, a CALS professor of animal sciences.

Working in rats, his team looked at changes in the size of the titin protein over the course of animal development—and immediately came across something strange. In most cases the titin protein shifted from a larger form to a smaller form during development due to natural changes in protein processing known as alternative splicing. But in some rats the titin didn’t change. It stayed big.

The team wondered if they’d mixed up the samples. “But we’d kept good track of things and, in fact, all of the weird samples were from the same litter of rats,” says Greaser. “Then the light bulb went off: There must be some genetic reason why these samples are different. These rats had a genetic mutation affecting the alternative splicing of the titin.”

But where was the mutation? They first checked the titin gene itself, but it was fine. With hard work, they were able to pinpoint the mutation to a little-studied gene called RBM20, which had been previously linked to dilated cardiomyopathy and sudden death in humans.

Dilated cardiomyopathy affects approximately one in 2,500 people. Sufferers have enlarged hearts, with thin walls, that don’t pump blood very well. People with the RBM20 mutation need heart transplants and, without them, tend to die quite early: between ages 25 and 30.

Scientists first linked RBM20 to hereditary dilated cardiomyopathy in 2009, but they hadn’t yet figured out how a faulty RBM20 gene worked—or didn’t work—to cause disease inside the body.

Greaser’s accidental discovery, as described in Nature Medicine, filled in the blank. In healthy individuals, the RBM20 protein is involved in the alternative splicing that helps trim titin down to its smaller, adult form. Without it, titin doesn’t get processed correctly, and the presence of extra-large titin in heart tissue leads to disease.

“Now doctors can analyze people showing symptoms of dilated cardiomyopathy, see if they’re carrying this mutation and factor this information into their treatments,” says Greaser. That treatment would probably start with careful monitoring to catch any further deterioration of the heart condition, Greaser notes.

Five things everyone should know about… Hazelnuts

1   They’re crazy nutritious and gluten-free. Hazelnuts are rich in vitamins (particularly vitamin E and B-complex groups of vitamins, including folates, riboflavin, niacin, thiamin) as well as dietary fiber. Like almonds, they are gluten-free. They also are rich in monounsaturated fatty acids such as oleic acid and linoleic acid, which help reduce LDL, the “bad” cholesterol, and increase HDL, the “good” cholesterol.

2   An exciting market beckons. Hazelnut oil serves various purposes in the kitchen (most notably as salad and cooking oil) as well as in cosmetics and pharmaceuticals. Kernels can be eaten fresh; used in baked goods, confections and other edibles; or ground for use in nut flours. An appetite is growing for spreadable hazelnut butters (Nutella, anyone?). And then there’s biofuel—the high oleic acid content makes hazelnuts an excellent feedstock for biodiesel and bio-industrial products.

3   They’re good for the environment. As a long-lived woody perennial, hazelnut bush plantings can be used to stabilize sensitive soils and erodible sites. Plantings do not have to be reestablished for decades. They can be closely associated with other high-diversity approaches to agriculture, including agroforestry and multicrop plantings. Since American hazel is a prominent native, there is no risk of invasiveness, and interrelationships to support Wisconsin wildlife are well established. In addition, hazel production readily integrates with small and medium-sized farming operations and family/cooperative farm unit organization.

4   Growers are emerging in the Midwest, including in Wisconsin. Southern Europe is still king in world hazelnut production, with Turkey leading at 75 percent. In the United States, commercial hazelnut production is still limited to the Pacific Northwest, where the climate allows for growing European cultivars. But a number of Midwestern farmers are trying their hand with two species, American (Corylus americana) and beaked (Corylus cornuta), that do well in cold climates and sandy soils. Surveys have identified about 130 hazelnut growers in Wisconsin, Minnesota and Iowa, with nearly 135 acres in production.

5   Important genetics work is underway. Farmers now growing Midwestern hazelnuts are also growing important data as there are, as yet, no commercially proven cultivars of hazelnuts in this region. Breeders are working to develop genotypes focusing on both pure lines of native American hazel and on hybrid crosses between European and American. By selecting from the very diverse native populations and by crossing European with American, they hope to develop a hazelnut shrub with the nut quality and yield of the European and the cold-hardiness and disease tolerance of the American.

 

The Midwest Hazelnut Development Initiative (UMHDI, midwesthazelnuts.org) is a regional collaboration that includes representatives from UW–Madison and UW-Extension.

Jason Fischbach, an agriculture agent with UW-Extension and a program partner with UMHDI, contributed to this piece.

Seeding an Organic Future

As a wicker basket containing old, faded seed packets made its way around the room, Tom Stearns asked each person to grab a packet and pour a few seeds into their hands. Some of the seeds were green and shriveled, others were tiny, shiny and black.

“Check them out,” encouraged Stearns, founder and president of Vermont-based High Mowing Organic Seeds, the only seed company in the nation to sell 100 percent organically produced seeds.

Addressing participants and speakers attending the Student Organic Seed Symposium at the Lakeview Inn in tiny Greensboro, Vermont, Stearns asked the group to consider what they could—and couldn’t—tell about the seeds just by looking at them. For many, all it took was a quick glance to know what plants they’d grow into.

But seeds hide an important part of their story beneath their coats. Just looking at a handful, it’s impossible to know who developed them and to what end. These details, however, have a lot to do with a farmer’s success.

Plant breeders have enormous influence over the varieties they develop, making key decisions about how, when and where they’ll grow best. Plants bred with high-input, conventional systems in mind (which generally employ chemical fertilizers and pesticides) tend to thrive in those systems. Likewise, those bred for organic systems tend to flourish in organic systems. Yet relatively little of this latter type of breeding work has been done over the past 50 years, mostly due to meager financial support. Today’s organic growers have difficulty finding organic-adapted seeds, and they are often forced to choose among conventional varieties.

To Stearns, this situation is ludicrous, on par with giving a beef cow to a dairy farmer. “You will get milk out of a beef cow, but not a lot—they haven’t been selected to produce milk. Beef cattle don’t have the right genetics for what dairy farmers are trying to do,” he explained to the group. “That’s what I think organic growers are dealing with. We don’t even know what we’re missing. The seeds we’re using aren’t genetically adapted to the kind of systems that we have.”

The most obvious solution is to have more plant breeders doing organic work. And, as Stearns looked around the room that day at the Lakeview Inn, he had reason to hope.

At a professional gathering about a year earlier, Stearns had met Claire Luby and Adrienne Shelton, graduate students in the Plant Breeding and Plant Genetics program at CALS, along with Alex Lyon MS’08, a CALS agroecology graduate now working on a doctorate at the Nelson Institute. During a dinner reception at the 2011 meeting of the Vegetable Breeding Institute—a Cornell University-based public-private partnership that fosters interaction between vegetable breeders and seed and food companies—the trio had shared with Stearns some of their experiences doing organic-focused work. While the students were excited about the work, they also felt unsure about their career paths and somewhat isolated and discouraged. Graduate students working in organic plant breeding, like their faculty advisors, are few and far between, and they lack the support network enjoyed by their conventional-focused peers.

“There are a lot of activities and events geared toward graduate students who are going to work at the bigger plant breeding companies,” explains Shelton. “But it’s really hard to connect with other students doing organic plant breeding because the organic seed industry is so small in comparison, and there are just a few of us—at best—at each land-grant university.”
Before dinner was over, a plan had sprouted to put on a symposium, dubbed the Student Organic Seed Symposium (SOSS), to give this scattered group of students a much-needed opportunity to come together and feel like part of something bigger—part of the new and growing agricultural movement that they comprise. Luby, Lyon and Shelton would organize it, with support from their advisors. Stearns would help host it in Vermont. There would be talks by experts, farm tours and a visit to High Mowing Organic Seeds. There would also be time to just hang out and get to know each other.

“The whole idea was to try to build these connections, to create a scientific community that could support us throughout our careers,” says Shelton.

It all came together in early August 2012, with 20 graduate students cupping seeds in their hands, eager to develop new plant varieties to meet the needs of organic growers.

Humans have been breeding plants since antiquity. Simply by selecting which seeds to save and plant the following spring, people make decisions that alter the overall genetic makeup of their crops. It’s a powerful technique, known as selection, that plant breeders still use to this day.

Modern plant breeders have many more tools at their disposal and bring a scientific approach to the whole process. A significant portion of the work involves making crosses. To do so, breeders pick two varieties with desirable traits, transferring the pollen from one to the pistil of the other, purposefully mixing together the good genes of both. The new plants created this way then go through years and years of re-crossing and selection until the breeder is satisfied with the final product. Only then is it released as a new variety. It’s a time-consuming process, taking up to a decade and sometimes more.

Crossing and selecting are classical plant-breeding techniques that look pretty much the same whether they’re used to breed plants for organic or conventional systems, so context is key.

“One of the underlying paradigms of plant breeding is you should breed for the conditions under which the crops are going to be grown,” says Bill Tracy, chair of the agronomy department at CALS.

And organic farms have a special set of conditions. Without chemical options to control weeds, insects and microbial diseases, organic farmers need varieties with a unique set of traits. For instance, they need varieties that are fast-growing and preferably dense-growing to out-compete and shade out weeds. They also need varieties with natural pest and disease resistance. At the same time, these plants need to produce a large, beautiful bounty.

“But to date there’s been very little breeding for organic conditions, so there are opportunities and needs out there that aren’t being met,” says Tracy, whose breeding program encompasses both conventional and organic sweet corn.

Class Act: Thinking big

For Ron Crandall, the study of genetics is personal. He wants to learn more about what causes cancer, a disease that has plagued many members of his family.

“In high school I started looking for treatments and to help get them into clinical trials,” says Crandall. “And from there I started to take some genetics classes and found I really liked it.”

Crandall is committed to that investigation for the long haul and wants to earn a dual MD/PhD degree in medical genetics at the University of Wisconsin School of Medicine and Public Health. “I hope it will prepare me to go out into the community and make a difference, not just in treating people who have cancer but other genetics-related diseases,” says Crandall, whose academic honors include a WALSAA Outstanding Sophomore Award and the Wallace Award for Genetics.

Crandall’s desire to serve takes him out of the lab and into the worlds of communication and campus leadership. In elementary school he began teaching himself computer programming and web design, drawn mostly by the challenge, he says, of finding easy-to-understand ways to convey complex information. He now heads his own web development and design business, SSII Designs, and also works as the website administrator for the Department of Genetics.

When he’s not studying or working, Crandall engages in student activities. He is a CALS Ambassador, charged with offering prospective students a peer’s view of CALS. He’s also president of the CALS student council and last semester was elected to the student services finance committee of the Associated Students of Madison (UW–Madison student government). There he plans to focus on a “metacouncil” initiative to create a much-needed representative body for all the student councils on campus, he says. Another project: to create a software enhancement to make DARS, the Degree Audit Reporting System students use to track requirements, easier to understand and implement.

One can’t accuse Crandall of not thinking big. The mystery is how he finds time for it. “A lot of sleepless nights,” he laughs. “I have this interesting schedule of doing 20-hour days. I’ll stay up until 4 a.m. or so, get a few hours’ sleep and then continue. And then on weekends I have huge naps.”