Drugs from bugs: Can microbes living on insects’ bodies yield new, effective antibiotics?

Facing an imminent global public health crisis, a UW-Madison research team has been awarded up to $16 million from the National Institutes of Health to find new sources of antibiotics to combat the rising number of deadly antibiotic-resistant infections.

CALS bacteriology professor Cameron Currie is part of the project. The work connects to his ongoing research on the symbiotic relationship involving certain insects that carry antibiotic-producing microbes on their bodies.

“The number of antibiotic-resistant strains has increased while the discovery of new antibiotics has slowed to a crawl. In fact, there are no new antibiotics,” said David Andes, professor of medicine and division chief of infectious diseases at the UW School of Medicine and Public Health.

In the 1980s, pharmaceutical companies were seeking Food and Drug Administration (FDA) approval of 10 to 20 antibiotics a year. Andes said there has been more than an 80 percent decrease in development of antibiotics since that time.

“The inability to mine novel natural resources for antimicrobials is a major bottleneck for attacking the drug-resistance crisis,” he said.

“Our team has developed a completely new paradigm for anti-infective drug discovery,” said Andes. “We have developed novel ways of finding new antibiotics and testing them rapidly. It’s a fresh approach catalyzed by complementary input from basic and physician scientists, microbiologists, chemists and pharmacologists who are thinking about the same problem.”

New Sources for Symbiotic Organisms

Andes is a co-principal investigator for a National Institutes of Health (NIH) Center of Excellence for Translational Research (CETR). The other is Cameron Currie from the department of bacteriology in the UW College of Agricultural and Life Sciences. Other members of the team are Michael Hoffman, Dr. Bruce Klein, Dr. Rod Welch and Harvard researcher Jon Clardy. The project grant runs for five years.

Traditionally, soil has been mined for antimicrobials that are used to develop antibiotics. But the UW-Madison team has been studying other natural products from animals, insects, plants and marine life. Andes said the study of soil has become a dead end because the same microbes are turning up over and over again.

Andes said the scientists are looking in new places for symbiotic organisms, those that have an interdependent relationship, that are highly likely to have a biological effect.

The scientists are traveling around the globe to harvest insects, plants and marine life. Once specimens are collected, Currie sequences the genome of each product and then decides if it is promising enough to merit further testing.

Tim Bugni, an assistant professor of pharmaceutical sciences, then uses a rapid and accurate method to determine if the microbes are making something never found before. A third part of the research attempts to coax an organism to make compounds by mimicking its environment.

 “We’ve also seen that the compounds that microbes are making are evolutionarily selected to be safe because they protect the animal from the environment, from infection threats,” said Andes.

The team is looking at two groups of relevant microbes: fungi associated with infections in immunocompromised patients like cancer and transplant patients, and bacteria responsible for the majority of U.S. hospital infections. The U.S. Centers for Disease Control and Prevention says more than two million drug-resistant infections a year are reported.

“There are patients in almost every hospital with infections that have absolutely no treatment options,” said Andes.

Building on Previous Research

The research builds on the work of the UW Antimicrobial Drug Discovery and Development Center, established in 2007. The Wisconsin Partnership Program and various NIH Challenge grants funded the research.

“We’ve been finding large numbers of new compounds at a rate greater than what the pharmaceutical industry ever did,” said Andes.

The goal of the Center of Excellence for Translational Research is to find one drug lead in each of the next five years.

Congratulations to these 2014 CALS staff and faculty award winners

Congratulations to the following recipients of the 2014 CALS staff and faculty awards. The awards ceremony will take place on Wednesday May 7th at 3 p.m. in the Ebling Symposium Center with a reception to follow. Please save the date and plan to attend and support this year’s group of award winners.

Classified Staff Awards

  • Dawn Irish – Animal Sciences
  • John Kemper – Animal Sciences
  • Ray Michels – Center for Dairy Research
  • Roger Quam – Arlington Research Station
  • Derald E. Stronach, Jr. – Arlington Research Station
  • Kim Trumble – Animal Sciences

Academic Staff Awards

  • Excellence in Research – Timothy D. Meehan, Entomology
  • Excellence in Leadership – Terry Jobsis, Animal Sciences
  • Excellence in Service – Anne Reynolds, Center for Cooperatives

Jung Excellence in Teaching Award

  • Douglas I. Rouse – Plant Pathology

Spitzer Excellence in Teaching Award

  • Ronald L. Russell – Animal Sciences

J.S. Donald Short Course Teaching Award

  • Bob Nusbaum – Animal Sciences

WALSAA Outstanding Advisor Award

  • Chris Day – Genetics

Excellence in International Activities Award

  • John J. Parrish – Animal Sciences

Pound Extension Award

  • David W. Kammel – Biological Systems Engineering

Pound Research Award

  • Douglas Weibel – Biochemistry

Arthur J. Maurer Extra Mile Award

  • James Nienhuis – Horticulture

Robert G.F. and Hazel T. Spitze Land Grant Faculty Award for Excellence

  • Kevin Shinners – Biological Systems Engineering

Bucky’s Butchery v. 2.0: Students brainstorm ideas for new campus meat shop

A few years from now, when patrons drop by campus’ new retail meat shop to buy some bacon or brats, they may no longer need to hunt for a parking space. If a design concept developed by a group of CALS and School of Human Ecology (SoHE) students becomes reality, the store would feature a handy drive-thru window.

That’s just one of many exciting ideas that students came up with during a recent design session hosted by SoHE’s design studies department and CALS’ animal sciences department, which houses the college’s meat science program. During the session, which brought together 21 students majoring in animal science, design studies, food science, art and computer science, the students worked in groups to brainstorm possible ideas for the look and feel of campus’ future meat store, which will open when CALS’ new meat science building is completed in 2017.

To kick things off, Roberto Rengel, professor and chair of design studies, provided coffee and inspiration, encouraging the students to focus on creating a beautiful and functional space, without getting bogged down by practical problems. “We want you to think about what the experience is,” he told them.

The students were then led through the design process by Amy Duwell Brockdorf, a design studies MFA candidate. Animal sciences faculty members Dan Schaefer, Jim Claus and Jeff Sindelar were on hand to provide background on the meat science program’s research and outreach activities and answer questions about plans for the new building.

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Some design concepts developed during the session.

The groups followed common principles of design thinking to develop their concepts. Along the way, they consulted Pinterest boards, YouTube playlists, Google Images and samples from the design lab for information and inspiration.

At the end of the session, the groups presented their top ideas, which included having the storefront look like an historic neighborhood meat shop, with brick walls and a bench out front; having a mobile meat cart to sell products across campus; affixing “meet-your-meat-processor” mini-profiles to products; providing educational materials related to meat processing; amongst many others.

Down the line, these ideas will be shared with the state-selected design firm chosen to work on the new meat science building. Whether or not any of their concepts end up incorporated into the final design, the students agreed that participating in the process was a valuable learning experience in and of itself.

Searching for coyotes and foxes amongst the Badgers

HollyH

Holly Hovanec tries
to locate a radio -collared fox spotted in Camp Randall
Stadium. Photo by David Drake.

When most students talk about the wild life at the UW-Madison, they talk about State St., Camp Randall and the Badgers. When Holly Hovanec talks about wild life on campus, she talks about State St., Camp Randall and the foxes. The wild canids have been spotted in both of those locations and in a long and growing list of other spots on or near campus.

Hovanec, a senior majoring in forest and wildlife ecology, is conducting a capstone research project looking at the home range, activity patterns, and general health of fox and coyotes on the UW-Madison campus. That includes the Lakeshore Nature Preserve, which includes the woods along the Lakeshore Path, the shorelines and marshes of University Bay, Picnic Point and areas adjacent to Eagle Heights.

Hovanec, who will be entering veterinary school in the fall, has been working closely with David Drake, associate professor of forest and wildlife ecology and Extension wildlife specialist.

“The idea,” Drake says, “is to learn more about this population in order to learn about the potential for a healthy coexistence with humans.”

“The idea,” Drake says, “is to learn more about this population in order to learn about the potential for a healthy coexistence with humans.”

Drake got involved in canid research in the preserve after being contacted by Cathie Bruner, the Lakeshore Preserve’s field manager. Bruner was looking for someone to study coyotes in the Preserve, after receiving more frequent reports of the animals from visitors.

In spring 2013, Drake worked with another wildlife ecology student, junior Lucas Rapisarda to study the habitat preferences and activity patterns of coyotes in the Preserve (read more). Using walking transects and camera traps, they determined that coyotes were most abundant in the Bill’s Woods area of the Preserve.

The next logical step, Hovanec says, was to radio-collar and monitor the coyotes to further evaluate their movements and activity. She and Drake decided to include fox as well, since there had been frequent sightings of a pair on campus. In fact, there’s a lot of speculation that the foxes are moving to the more peopled parts of campus to avoid the coyotes. Coyotes kill foxes.

The project was a great fit for Hovanec. “I was looking for something that would take a lot of initiative,” she says. “I wanted something that was outside and hands-on. I wanted there to be a veterinary component.

The veterinary component was accomplished with the help of UW veterinarian Mike Maroney. He was on hand each time a fox or coyote was captured and collared, showing Hovanec how to give the animal a physical exam and take blood and fecal samples to evaluate its health. Tests on three animals, notes Hovanec, revealed they carry common intestinal parasites; were exposed to parvovirus in the past (but aren’t necessarily active carriers of the virus); and are free of tick-borne diseases. All in all, they don’t appear to pose a risk to local pets or other wild animals.

Hovanec conducts daily searches of the collared animals. The coyotes seem to be most active at night and in the early morning. On bitterly cold and windy days she discovered that the coyotes tended to retreat deep into the cattails of the University Bay and Class of 1918 marshes. On nicer mornings, she has found them in Eagle Heights Woods and the Village of Shorewood Hills.

One morning Hovanec couldn’t locate one of the coyotes. Later that day Drake received a call from a Middleton resident who had spotted a coyote crossing the frozen lake with something around its neck. The coyote came back to campus the following day. But sadly, another trip across the lake didn’t have a happy ending. Two weeks ago one of the collared coyotes was hit and killed by a car north of Lake Mendota on Highway M.

“It’s too bad,” says Drake, “but it’s a piece of information we need to know. We’ll keeping adding those pieces of information together to get a better picture (of what’s happening with these animals).  It happens, and it’s important to find that stuff out.”

The disappointment of losing a research animal was part of the learning process for Hovanec. Another lesson was about technical failures and the need to overcome them. Radio signals from the fox have been difficult to pick up consistently—she and Drake suspect the collar isn’t working—so she has been relying on reports of sightings to monitor him.

Fortunately, there are lots of eyes out there. The fox has a much wider home range than the coyotes and seems to be active at all times of the day. He was first spotted near the Madison Gas & Electric power plant on E. Main Street; then at the Hasler Laboratory of Limnology at the east end of the Lakeshore Preserve. In March, a pair of foxes were spotted frolicking in Camp Randall Stadium. There’s also a report of a fox trotting up State St. in the middle of the day, and another of a fox with a chicken in its mouth on S. Mills St.

Hovanec hopes her research will yield information benefiting the safety and health of Preserve users, their pets, and the wild canids. It is possible that the information she gathers could be used to draft plans of management or conflict avoidance, should an issue arise in the future.

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This is an expanded version of an article in the spring 2014 issue of the Lakeshore Nature Preserve Newsletter written by Preserve outreach specialist Bryn Scriver and Holly Hovanec. 

 

 

 

Climate change puts spotlight on Antarctica’s peculiar soils

Among his other accomplishments, UW-Madison soil scientist Jim Bockheim helped convince his colleagues that Antarctic “soil” really was soil—no quotation marks required. Soils specialists had debated the point for about 70 years, beginning when explorer Ernest Shackleton bought back samples of loose, sandy, and grayish material collected from the surface of the coldest continent. In 1994, Bockheim led an international committee, which, after three years of intense debate, established a 12th soil order specifically for permanently frozen soils: the Gelisols. Bockheim continues to research Antarctic soils. Not surprisingly, the focus is on the impacts of climate change. Read more in this article on the Soil Science Society of America website.

 

Career objective: A healthier world

There are thousands of undergraduates on campus who, in terms of their future careers, consider themselves “pre-health.” For some, the motivation is acutely personal. As a child, Kevin Cleary BS’13 (biology) felt an urgent need to help as he watched his father deal with recurrent brain tumors. “By age 11, I knew I had a future in health care,” says Cleary. Many others aren’t yet sure what role they will play, but they are eager for guidance on how to use their majors to address an array of global problems including hunger, disease, poverty and environmental degradation. Says senior biochemistry major Yuli Chen, “I want to make an impact on people, and I believe that every person has the right to be provided basic necessities such as clean water, education and food.”

Read how the CALS-based Global Health Initiative is helping these and other students prepare for careers that address these challenges.

A look at CALS organic ag research

UW-Madison scientists are engaged in a wide range of research related to organic agricultural production practices, according to a new report released on Feb. 28 at the 2014 MOSES Organic Farming Conference in La Crosse.

Organic Agriculture in Wisconsin: 2014 UW-Madison Research Report is available on the CIAS website.

The report, published by the Center for Integrated Agricultural Systems (CIAS) and the Wisconsin Department of Agriculture, Trade and Consumer Protection  summarizes 23 studies conducted by CALS researchers in partnership with farmers across the state. The scientists are evaluating production practices for many of the state’s main agricultural products—dairy forages and pasture, soybeans, potatoes, vegetables and fruits, among others—as well as farm management and marketing.

The report also takes a more in-depth look at how some of the organic research projects have benefited the state’s farmers. For example, UW plant pathologists Ruth Genger and Amy Charkowski are working with producers across the Upper Midwest to improve organic seed potato production and develop new organic varieties suited to the region. Those producers include Kat Becker and Tony Schultz, who tested the UW scientists’ Papa Cacho potato on their Community Supported Agriculture farm in Marathon County.

“This variety did really well in a horrible drought,” Becker reports. “It’s done well in freezing cold, low-nitrogen environments. And it’s commercially viable for us, giving us a variety that no one else has.”

The report also profiles organic no-tillage research being conducted by Erin Silva, a scientist in CALS agronomy department and CIAS. No-till practices require less fuel and labor, reduce erosion and improve soil, but because conventional no-till techniques require herbicides, organic farmers have not been able to capture the benefits, Silva points out. For the past eight years, she has been working on a no-till system that involves planting a cover crop in the fall, killing it in the spring with a mechanical roller/crimper, then planting a grain or seed crop directly into the remaining mulch.

This system has worked well for organic dairy farmer Jim Miller, who used it to plant soybeans into a rye cover crop on his family’s fifth-generation farm near Columbus. “That was probably the nicest field we have ever seen,” he says. “There might have been five weeds in the entire field. It was beautiful and yielded very well. If the stand of rye is thick and the yield is good, this definitely translates into savings.

This is an appropriate year to highlight UW organic agriculture research, notes CALS Dean Kate VandenBosch in the report’s introduction. The college, which itself turns 125 in 2014, is celebrating the 25th anniversary of two key initiatives focused on sustainable and organic agriculture. One is CIAS, which was started in 1989 to build UW sustainable agriculture research programs. The other is the Wisconsin Integrated Systems Cropping Trial, established to investigate the sustainability of diverse rotations and other low input measures. WISCT, which is profiled in the report, is one of the nation’s longest-running trials that includes organic management.

While the UW’s organic research has clear benefits for the state’s 1,100 organic producers, it also provides a lot of information that can help those who employ conventional farming practices, points out Extension entomologist Russell Groves, who evaluates both organic and conventional pest control practices for use in vegetable production.

“The organic producer has to be especially attuned to varieties that resist or tolerate pests more, and non-chemical means of control—things like exclusions, row covers, trap crops, sanitation—but our commercial growers can certainly benefit from the same information,” Groves says.

 

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Garden fever? You can’t plant, but you can plan.

You’ve just got to believe. Days are getting longer, and (really) they’ll be getting warmer. So while planting season may be a ways off, it’s always planning season. CALS and UW-Extension horticulture specialist Eileen Nelson has a few words of advice for those of you whose green thumbs are throbbing.

What should I be doing right now to plan for my garden?
Gardening is a four season hobby. While we aren’t actively out in our gardens, now is the time to dream and to plan for the growing season. If you had a garden last year, think back to what worked and what didn’t work. Visit your nearest garden center to see what seeds they have stocked for the coming season, look over the items you think you might need, make lists and start planning. Now is also a good time to peruse some of UW Extension’s publications on gardening, including “The Vegetable Garden,” that are available from the Learning Store at UW Extension.

Love those seed catalogs! How do I pick varieties for my yard?
Your first step to selection is understanding your growing conditions. Most vegetable seed selections at local garden centers are suited to our general location, but some have specific light, soil pH and fertility, and water requirements. When the ground thaws, however, it’s smart to do a soil test. Knowing what your soil is like and what you need to do to prepare it is a first step to success. A soil test will tell you how much fertilizer you might need to add, if any. So add this to your to-do list, and contact your county Extension office if you need help or have questions.

And once I’ve got my soil figured out?
Additional information on choosing vegetable varieties can be found in the publication Vegetable Cultivars and Planting Guide for Wisconsin Gardens.

My spades and hoes are sharp. I’m ready. How soon will I be able to plant?
You have to be patient. In those first snow-free days of “pre-spring,” our common sense seems to go right out the window and the inclination is to start planting. And many box stores have plants ready for sale in late March and early April, further causing us to jump the gun. But experienced gardeners know that there is still some time to go. Mother Nature can be fickle! If you look at USDA plant hardiness zone maps and information on last average killing frost days in Wisconsin, you will see that for much of Wisconsin we can have a killing frost any time in May. The urge may be to put plants in the garden, but for many that do not tolerate cool to cold temperatures, the old adage of not planting anything before Memorial Day (May 31) still holds true.

OK, I get it. For now I’ll just garden on paper. Who can help me with that?
Good idea. Planning before you plant will ensure success and there’s no reason not to get started. Local garden centers are one of your best resources for information, education—and a measure of common sense! They want you to succeed and will not let you put a plant or seed in before its time. And of course, you can find additional resources for learning about gardening at UW Extension Horticulture or by contacting your county Extension agent.

 

Modified poplars convert to ethanol more efficiently

For decades, John Ralph’s group has been focusing its expertise in biology, chemistry and engineering on one of the most persistent hurdles to a bio-based fuel economy: lignin. As the organic polymer that binds plant cell, vessel and fiber cell walls, lignin resists chemical and enzymatic processing and thus acts as a structural barrier to converting biomass into liquid fuels.

So-called “second-generation” biofuels, which derive from dedicated energy crops such as switchgrass or poplar trees, are all lignocellulosic, meaning their woody cell walls contain lignin polymers. Ralph, a University of Wisconsin–Madison professor of biochemistry and biological systems engineering and the Plants Leader within the Great Lakes Bioenergy Research Center (GLBRC), recently collaborated with researchers at Michigan State University, Ghent University in Belgium, and INRA in France on a field trial of lignin-modified poplar trees to measure any increase in ethanol yields.

January 14, 2014 PNAS Cover

The group’s paper, “Improved saccharification and ethanol yield from field-grown transgenic poplar deficient in cinnamoyl-CoA reductase,” appeared recently as a cover article in the Proceedings of the National Academy of Sciences, and reports on a field trial of poplars in which cinnamoyl-CoA reductase (CCR), an enzyme known to play an important role in lignin biosynthesis, is genetically down-regulated or decreased.

Preliminary data on the group’s lignin-modified poplars had been encouraging. “Basic mechanistic data and performance data from green-house grown poplars and Arabidopsis suggested that the CCR lines’ improved performance could be due to structural changes to lignin, in addition to lignin reduction,” Ralph says.

Although the extent to which lignin was suppressed varied between poplars, the study showed that down-regulating CCR resulted in a 20 percent higher ethanol production from un-pretreated biomass and, in the strongest cases of suppression, a 160 percent higher yield.

“We applaud our European collaborators for undertaking these extensive, replicated, and difficult field trials on one of the most promising lignin-altered lines,” Ralph says. “These trials provide real-world productivity and conversion data comparisons while at the same time beginning to address sustainability and environmental issues.”

The use of strong CCR down-regulation, however, also had an adverse effect on poplar yield. The lignin-modified trees grew less quickly than their non-modified counterparts. Further studies will likely focus on overcoming the yield penalty associated with CCR down-regulation, or on using a different enzyme, such as the CAD-enzyme, to achieve a more uniform suppression of lignin. Both Boerjan and Ralph are optimistic that further refinements to the paper’s method could improve the un-pretreated ethanol yield of poplar by 50 to 100 percent.

“A number of current and emerging lignin-altered lines have the potential to lower the severity of expensive biomass pretreatment, which would improve the overall energy balance and sustainability of converting biomass to biofuels,” says Ralph.

This research was funded partially by The Great Lakes Bioenergy Research Center (GLBRC), one of three Department of Energy Bioenergy Research Centers created to make transformational breakthroughs that will form the foundation of new cellulosic biofuels technology. For more information on the GLBRC, visit www.glbrc.org.

This story was originally published on the GLBRC website.