MnDRIVE program catapults undergraduate researcher to national stage

Undergraduate researcher Tamirat Ali

By Deirdre Manion-Fischer

Tamirat Ali spent last summer growing fungi in Jonathan Schilling’s lab at the University of Minnesota. He was studying ways to mitigate climate change by measuring the ability of fungi to capture methane. The technique, called biofiltration, relies on fungi to capture pollutants and bacteria to degrade them. While other research has focused on optimizing bacterial degradation, Schilling and Ali suspected they could find a more efficient fungus to optimize methane capture.

Over the course of the summer, Ali injected methane into glass vials containing tiny blocks of wood inoculated with fungi. Twenty-four hours later, he measured the decrease in methane. One type of white-rot fungus (Ganoderma lucidum) used in traditional Chinese medicine worked better at capturing methane than the species widely used in bioremediation (Pleurotus ostreatus). His success earned him a competitive travel award to attend the Emerging Researchers National (ERN) Conference where he presented his results in Washington D.C. earlier this month.

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Two U startups named among “Best University Startups 2016”

Sun shining over city street

Two University of Minnesota startups received national recognition today for their potential to create jobs, advance technology and meet societal challenges in industry and the environment.

Innotronics and Minnepura, both launched by the U’s Venture Center, were named among the 35 “Best University Startups 2016” by the National Council of Entrepreneurial Tech Transfer (NCET2), an association of university startup officers. The startups were chosen from a group of 200 submitted companies launched by universities across the U.S.

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Improved method will enhance microbiome research

Researchers at the University of Minnesota have developed an improved method for analyzing the communities of bacteria and other microorganisms that live on or inside humans, animals and the environment.

Understanding how these communities, called microbiomes, affect the way a body or ecosystem functions can lead to innovations in a wide variety of fields, including new treatments for antibiotic-resistant diseases, eco-friendly fertilizers for agriculture and natural methods for removing contaminants like sulfates from local waterways. More accurate ways to detect different types and concentrations of microorganisms will lead to better, more reliable data in the rapidly expanding field of microbiome research.

The research team, led by U of M Genomics Center Director Kenneth Beckman, Ph.D., highlighted in a study published in Nature Biotechnology that better methodology will lead to more results that can be reproduced and that translate across studies, along with fewer misleading conclusions. Continue reading

Exploring gut bacteria’s role in disease and human health

Family having a meal

For as long as humans have been around, the normal function of their intestinal tract has relied on the complex interplay of trillions of microscopic organisms, which in turn thrived off of the food we ate. Now, through pressure from modern diets and medicines, that longstanding partnership may be falling out of balance.

Dr. Alexander Khoruts, medical director of the University of Minnesota Microbiota Therapeutics Program, highlighted at a recent lecture how some of the growing health challenges we face today could stem from the changing composition of the microbes in our intestines. Microbes constitute an integral part of the human body and interact with it in complex ways. Recent research suggests that the diversity of microbes in people is shrinking and this may be causing significant health problems in our population. “The Evolving Human Microbiome,” hosted by the U’s Consortium on Law and Values in Health, Environment and the Life Sciences on Feb. 17, explored the ramifications of our bodies’ changing microbial communities.

“We’re discovering that these microbes are important for our health and for disease,” Khoruts said. “For the most part, it has been a mutualist relationship — what’s good for them [the bacteria] is good for us. But these relationships can go wrong.” Continue reading

Treating diabetes with beneficial bacteria


University of Minnesota researchers are on a mission to treat diabetes, and they’ve enlisted a few trillion microscopic helpers.

In place of drugs or surgery, a team of researchers is studying how to improve diabetes patients’ insulin sensitivity by introducing trillions of beneficial bacteria into their intestines. Researchers believe this unusual approach, conducted through a fecal microbiota transplant, could improve how the body regulates blood sugar, the central problem in diabetics. The project is part of MnDRIVE (Minnesota’s Discovery, Research and InnoVation Economy), a $36 million biennial investment by the state that aims to solve grand challenges. As a part of MnDRIVE’s Transdisciplinary Research Program, the project will bridge multiple fields of research and bring together experts from across the U to work on the same clinical trial.

Patients with diabetes have too much glucose in their blood, which leads to a host of serious health problems, from heart disease to obesity. Dr. Alexander Khoruts, a gastroenterologist at the U of M and lead principal investigator on the project, said the right balance of bacteria has the potential to improve the body’s energy metabolism, in part by enhancing insulin function. Insulin drives glucose from blood into cells of the body.

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Startup ex machina

Photos by Andria Waclawski

BIO 2014: showcasing research, forming partnerships


At the University of Minnesota, advances in the biological sciences regularly yield new and exciting ways to improve the technology that benefits our lives.

Later this month, the U will have a chance to showcase its discoveries and connect with other innovators on a global scale at the 2014 BIO International Convention, hosted by the Biotechnology Industry Organization. More than 10,000 people from leading biotechnology and pharmaceutical companies across the globe, along with academic institutions and research labs, will converge in San Diego June 23-26 for the annual event to form new partnerships and understand emerging opportunities in the industry.

The U’s prominence in biotechnology is one part of a thriving statewide ecosystem. Minnesota is a national leader in bioscience innovation, ranking third in bioscience-related patents and fifth in venture capital investments per one million residents, according to a 2010 report. The state’s Department of Employment and Economic Development (DEED) notes in a fact sheet on the industry that bioscience supports tens of thousands of jobs statewide. Continue reading

Ancient remedy a promising cure for Clostridium difficile


A team of researchers at the U of M have revived an ancient medical treatment to address a severe gastrointestinal illness and have developed ways to standardize the procedure.

The process, dubbed “fecal microbiota transplantation” transfers healthy bacteria from one person’s intestine to another person where the healthy bacteria have been depleted. It’s very effective for people suffering from Clostridium difficile, also called  C. diff, an opportunistic pathogen that takes over when antibiotics wipe out “essential and symbiotic” bacteria in the gut.

Although the infection itself is triggered by antibiotics, the standard treatment for C. diff has been to give even more antibiotics, which can trigger a vicious cycle of recurrent C. diff. Normally, C. diff can be held at bay by resident bacteria in the colon. When antibiotics kill off the normal bacteria, C. diff flourishes, releasing toxins that cause diarrhea, fever, nausea and abdominal pain. Subsequent courses of antibiotics suppress, but don’t kill C. diff, and it often reemerges. In severe cases, patients can waste away and die.

A mutant monster of our own making

Fecal microbial transplantation is effective in treating refractory C. diff infections. The donor feces contain healthy populations of bacteria that repopulate the gut, and hold C. diff in check. However, explains Alexander Khoruts, M.D., associate professor of medicine at the University of Minnesota, the current process is unpleasant and unregulated. Essentially, a donor must provide feces which are implanted via colonoscopy, nasal tube or enema.

“In this form, the treatment has a long history. It goes back as far as 4th Century China, and was introduced into Western medicine by Dr. Eisemann and his team in 1958. Surgeons trained in 1960s remember Dr. Wangensteen using the procedure at the U of M. (Wangensteen was chairman of the U’s Surgery Department from 1930 to 1967.) Then we learned how to treat C. diff with antibiotics. However, the organism has since evolved, acquired more resistance to antibiotics and has become even more toxic.”

Khoruts and colleague-collaborator Michael Sadowsky, director of the U’s BioTechnolgy Institute, have recently invented a process that is more reliable and can be standardized, making the treatment more widely available to patients suffering from C. diff.

Their invention is just in time, because C. diff infections have surged over the past decade. The tenacious and deadly illness now affects about 340,000 people each year. In fact, explains Sadowsky, “On average, patients have had the infection for up to a year with six relapses. Estimates are that 14,000 to 30,000 people die each year from it. The percentage of recurrence of C. diff is twenty to thirty percent. With each course of antibiotics, the subsequent relapse goes up another twenty to thirty percent.”

Care is estimated at $2,500 to $7,000 per patient. In some cases, colectomy is necessary. The infection, traditionally confined to hospitals and nursing homes, is now spreading into the community.

Fortunately, the process Khoruts and Sadowsky have invented is a likely candidate for broad medical use. The team was the first to document that the transplanted bacteria actually survive in the new host (the patient), according to Khoruts. This helps build credence for the treatment. It is 92 percent efficacious and is vastly superior to the antibiotic suppression method. And the standardized, streamlined method will make the application more likely to be approved by the FDA.

Sadowsky adds, “In the old practice, feces were directly transplanted. Our innovation is in separating the bacteria from the donor feces, freezing it, and providing in essence a universal material for use in patients. Our donors have been tested for disease, and we use the same paradigm as blood donation, with some additional restrictions. For example, we don’t accept anyone using a prescription medication or who has been traveling abroad.”

Process recently licensed

CIPAC Limited, an Australia-based company with subsidiaries in California, is working with the U of M to advance the technology and bring a safe, effective treatment to market. It has licensed the technology and is working with the FDA and the university’s team to begin clinical trials.

The FDA’s recent announcement should accelerate interest in the process. Khoruts notes, “Our group has been the leader in standardization of this procedure in the U.S. We have been doing it in steps and our latest advance is moving material preparation out of the research laboratory to an FDA-registered facility at the university where the process is done in accordance with the FDA’s GMP (good manufacturing practices). We think that this is how the procedure will continue to develop. In the short term the FDA involvement very likely will result in decreased access to this procedure. However, once the process is streamlined, as we’re trying to do, it will become part of mainstream medicine and access will become greater than before.”

Post by Vincent Hyman, a freelance writer based in St. Paul, Minn.

Originally published on Research @ the U of M.

Heated sludge helps defeat superbugs

Water treatment facility

You’ve probably heard of “superbugs”—bacteria that are resistant to numerous antibiotics.

They’ve cost many lives and billions of dollars. And part of the solution could be as simple as treating our waste to a nice hot bath.

Timothy LaPara, Ph.D. of the University of Minnesota’s Department of Civil Engineering and a member of the BioTechnology Institute, has interests in wastewater microbiology and antibiotic resistance. He’s combined these to address a pandemic that threatens to return the world to a pre-penicillin era.

A global problem

Worldwide, about 440,000 new cases of multidrug resistant tuberculosis occur each year, resulting in at least 150,000 deaths, according to the World Health Organization. Resistance to streptococcus pneumonia is also on the rise. And the infamous MRSA—an antibiotic-resistant staph infection—has become a global problem.

“In the U.S.,” explains LaPara, “we spend twenty to forty billion dollars annually coping with antibiotic resistance. Fifteen to twenty thousand people die from MRSA resistant infections.”

The rapid growth of resistant bacteria appears to be an unintended consequence of the ways we use antibiotics. When antibiotics are used routinely, a few naturally resistant bacteria survive, and these go on to produce more resistant bacteria. In the U.S., about 80 percent of the total antibiotic use is on the farm, where animals routinely receive antibiotics to prevent disease and encourage growth. In healthcare, patients often receive antibiotics they don’t need or do not finish their antibiotic courses. We also widely use antibacterials such as triclosan in consumer soaps and other products.

The result is a burgeoning population of antibiotic-resistant germs. Because bacterial DNA readily transfers among bacteria, concentrations of them—as occurs in human sewage and animal waste collection sites–can result in dense communities of resistant bacteria.

Changing the patterns of use of antibiotics on farms, in health care and consumer products is part of the solution, but can be politically fraught.

Killing the bugs where they concentrate

LaPara’s proposed solution complements these existing approaches and kills the bugs where they concentrate: in human and animal waste.

When raw sewage is treated, it leaves behind a sewage sludge called biosolids. LaPara has found that raw sewage has 50,000 times more antibiotic resistant genes than what’s found in a typical river. But even after treatment, the remaining biosolids are thick with antibiotic resistant genes. These resistant bacteria potentially find their way into the human population through a variety of transmission means: they can be contained in fertilizer (one of the primary uses of biosolids), spread via the air, and included in the foods we consume.

Biosolid dewatering

But heating biosolids can kill the bad guys. Here’s where the engineering tricks and microbiology magic come in. Sewage plants use naturally occurring bacteria to digest waste and a byproduct of that process is methane gas. Some of these plants use the methane to heat the biosolids to body temperature, which is perfect for the growth of sewage-munching bacteria, but also ideal for growing resistant bacteria.

“If we raise the temperature to about 130 degrees Fahrenheit, different, heat-loving bacteria will digest the biosolids,” explains LaPara. The higher temperatures kill off the resistant bacteria, but still generate the methane needed to keep the plant heated up. It’s a win-win.

That was the theory. LaPara’s lab tests showed that heated biosolids have 1/100th the amount of resistant bacteria as compared to unheated biosolids. To find out if the process has real-life promise, LaPara tested the sludge from a treatment plant in Duluth that already heats its digesters to 130 degrees. Sure enough, its residual sludge had 1/10th to 1/100th the concentration of resistant bacteria in biosolids from plants that operate at lower temperatures.

Says LaPara, “If I could get people to use the best treatment, I would have them do it like Duluth. We spend about fifteen billion dollars a year in the U.S. on wastewater treatment. For an additional cost of less than 10 percent, we could switch to a higher temperature. This could help end the resistant bacteria problem very quickly.”

Making the most of a hot mess

But ridding ourselves of superbugs will take additional effort. “Everything we do with human waste, we could also do with animal waste,” says LaPara. He notes that more farms are beginning to generate methane from their animal waste for use as an energy source. The process could be used to kill off the antibiotic bacteria in animal waste as well, making the waste safer for use as fertilizer.

LaPara says there are a number of steps needed to get this process adopted widely. “Ten years ago, very few people were looking at this. Many of the research techniques we’re using were only developed in the last decade. This is not yet in the public health arena. But over the next ten years, I’d like to see our waste treatment community move toward more aggressive treatment of biosolids. We’ll reduce resistant bacteria and other pathogens as well.”

Post by Vincent Hyman, a freelance writer based in St. Paul, Minn.

Originally published on Research @ the U of M.

Biotechnology Resource Center scales up innovations


Biotechnology probes the properties of the microscopic, sometimes to great reward. But the most exciting discoveries can’t impact society unless they hold up at a commercial scale. The Biotechnology Resource Center in the BioTechnology Institute houses the equipment and expertise needed for companies to put discoveries to the test in larger batches.

BRC offers state-of-the-art lab space and equipment to biotechnology companies of all kinds, from small startups to global corporations, working on biotech endeavors that run the gamut. The lab’s competencies lie in process scale-up and fermentation for biological materials, and their rates make biotechnology equipment accessible to innovators of all kinds.

“We can work with industry to provide them with services to get an idea off the ground, or to do work they wouldn’t want to do or couldn’t do at their main lab,” says Tim Tripp, director of BRC. Continue reading