Four Miami University microbiologists — who make up the department’s new microbiology physiology research cluster — collaborate on projects with each other and with more than a dozen researchers from other universities.
Together, they are working on five projects funded by more than $5.2 million in recent grants from three national agencies. Study sites range from nearby Acton Lake to Antarctica.
Microbes — the first living creatures on Earth — are microscopic, single-celled organisms found almost everywhere on Earth including on and inside you.
Microbes make up more than 60 percent of Earth’s biomass.
An estimated 2-3 billion species of microbes share our planet — but fewer than 0.5 percent (that’s still 10 million) have been identified.
Microbes generate at least half of the oxygen we breathe.
From the human gut to the atmosphere
The research projects of Rachael Morgan-Kiss, Annette Bollmann and D.J. Ferguson, associate professors of microbiology, and Xin Wang, assistant professor, explore microbes in projects including:
Microbial engineering for the production of biofuels.
Manipulating microbial communities to function more efficiently for wastewater treatment.
Studying extremophiles to create new engineering targets for artificial photosynthesis.
Contributing to long-term research on climate variation in the South Pole.
Human gut microbes.
By the numbers:
Four faculty mentor nine graduate and 11 undergraduate students on these projects.
They collaborate with 13 researchers from 11 universities.
One internationally-known artist, Xavier Cortada, is working with students and researchers.
Read their stories:
Click on the links to read their stories in Miami’s Campus News.
Some years, as much as 20% of the U.S. population becomes infected with the influenza virus, according to the Centers for Disease Control. Most people who get the flu experience mild illness that amounts to little more than an unpleasant inconvenience. However, some cases of the flu can be very severe, and even mild cases can be life-threatening for young children, the elderly, and those with certain medical conditions. For these vulnerable patients, early treatment with antiviral drugs is critical.
Yet, to be treated, the flu must first be diagnosed, and doing that is not as easy as many clinicians would like. Although there are two different kinds of tests that can be used to diagnose the flu while a patient is in the doctor’s office, these tests don’t catch every case. A third test is more accurate, but requires processing and analysis in a lab, making it more expensive and time-consuming as well. The net effect is that critical treatment may be delayed, if it happens at all.
Xiao-Wen Cheng is working on a better way. An associate professor of microbiology at Miami University, Cheng’s innovation is to detect a virus directly, using a method that doesn’t require extracting viral RNA. Detecting a virus directly is more diagnostically reliable than detecting the antibodies a patient has developed in response to a viral infection – the method used in currently available rapid influenza diagnostic tests (RIDTs) – because patients in the very early stages of infection may not yet have developed antibodies. Cheng’s method is also cheaper and faster than direct-detection lab tests that rely on RNA extraction.
The key to Cheng’s innovation is an engineered enzyme known as RTAKAS-mix. RTAKAS-mix was initially inspired by an enzyme produced by a group of German scientists. That enzyme – which Cheng learned about in a paper the team published – was capable of detecting certain viruses. However, as Cheng discovered when he replicated it, the enzyme was not very robust, so its usefulness in practical applications was limited.
To benefit clinicians and patients, Cheng knew a useful viral diagnostic enzyme would have to be sturdy enough to withstand some harsh conditions. “Diagnostic test kits have to be shipped from the manufacturer to doctors’ offices,” he says. “They’re transported by truck across the country all year. It can be more than 100 degrees Fahrenheit inside a truck in the summer, and the test kit has to be able to survive that.”
Since the enzyme originally created by the German team was not that robust, Cheng and his team put the enzyme through a series of mutations, finally developing the stable, long-lived RTAKAS-mix, which can withstand temperatures up to 54°C (129°F) for at least two days.
Once his lab had an optimized enzyme, Cheng needed a path to commercialization, so he applied and was accepted to I-Corps@Ohio, a program that uses methodologies pioneered by the National Science Foundation in its Innovation Corps (I-Corps) program. As its website explains, I-Corps@Ohio is “a statewide grant-funded program to assist faculty and graduate students from Ohio universities and colleges to validate the market potential of their technologies and launch startup companies.”
In addition to Cheng, who serves as the project’s principal investigator, the I-Corps@Ohio project team includes Michael Nau, a senior microbiology major and management minor who serves as the entrepreneurial lead; Hui Shang, a graduate student in the cell, molecular, and structural biology program who serves as the co-entrepreneurial lead; and Dan Rose, an angel investor, entrepreneur, and I-Corps@Ohio instructor who serves as the entrepreneurial mentor.
Together, Nau and Shang interviewed more than 100 potential customers – nurses, doctors, veterinarians, and other clinicians – to learn about their day-to-day practices and what they need from a viral diagnostic tool. Some of the interviews were via phone or email, but many of them were in person, with Cheng driving Nau and Shang to hospitals and doctors’ offices all over the Columbus area.
One insight that came from the interviews surprised Cheng: when it comes to flu, clinicians don’t really care about viral load, or how many copies of the virus are circulating in a patient’s body. Cheng’s test is so sensitive it can detect the presence of a single virus particle in a sample, and that’s all that’s needed for the flu – a simple infected/not infected diagnosis is enough to make appropriate treatment decisions.
But Cheng’s test can also determine viral load, and he learned from the interviews with clinicians that viral load is very important to treatment decisions for certain other viral infections, including HIV. Cheng has already used RTAKAS-mix to detect FIV, a feline virus similar to HIV that causes an AIDS-like disease in cats. Now he’s heading back to the lab to see if he can apply his solution to develop a direct-detection test for HIV – and HIV viral load – that doctors can use in their offices while patients wait.
At the same time, Cheng and his I-Corps@Ohio team will look for an investor to form a company that will manufacture and market a flu test kit using RTAKAS-mix. “The company will probably operate for a short time before it is bought by a larger company,” he says. “That’s the business model, to attract investment through acquisition.”
Being involved, however briefly, in the management of the new start-up company will provide Nau and Shang with valuable experience. Even negotiating their eventual exit from the company will become part of a roadmap they can use to navigate future entrepreneurial ventures.
That’s important because commercialization of biomedical innovations is as critical to improving the lives of Ohio’s citizens and ensuring the vibrancy of its economy as the scientific discoveries behind those innovations. After all, as Cheng puts it, “If technology stays in the lab, it creates no value.”
Written by Heather Beattey Johnston, Associate Director of Research Communications, Office for the Advancement of Research and Scholarship, Miami University.
Photo of Xiao-Wen Cheng by Jeff Sabo, Miami University Photo Services. Photo of I-Corps@Ohio project team by I-Corps@Ohio.
During infection many types of bacteria organize into naturally occurring three-dimensional structures called biofilms. Bacterial biofilms cause chronic infections, because they show much greater resistance to both antibiotics and the immune system than their free-living counterparts.
Biofilms allow the bacteria to adhere to a variety of surfaces, living or nonliving. Some bacteria form biofilm infections of medical devices such as catheters and mechanical ventilators; once the device is colonized, infection is almost impossible to eliminate.
There are currently no approved treatments for biofilm-related infections: Though any bacterial infection can be treated with antibiotics, as of yet there are no specific methods to make them more effective against biofilms.
Microbiologist Mitchell Balish, associate professor of microbiology at Miami University, and his graduate students are working to understand the features of Mycoplasma pneumoniae biofilms and determine how their development might be inhibited.
A recent study by Monica Feng and Steven Distelhorst, graduate students in Balish’s laboratory, sheds light on how biofilms of the bacterium M. pneumoniae organize themselves.
Their study also highlights the anti-biofilm potential of a group of chemical compounds called 2-aminoimidazoles (2-AIs) that could lead to improved treatment of patients.
Mycoplasma pneumoniae is a prevalent bacterium that is a leading cause of bronchitis and pneumonia, especially in children and young adults. It is also linked to asthma, autoimmune diseases and central nervous system infections.
It infects millions around the world on an annual basis and is responsible for more than 100,000 hospitalizations per year in the United States alone, Feng said.
In the last 20 years M. pneumoniae has gone from being entirely susceptible to ordinary antibiotics to being almost completely antibiotic resistant in populations in certain parts of the world, particularly East Asia, Feng said.
In the face of rising antibiotic resistance, development of new treatments for mycoplasmal diseases will rely on a deeper understanding of the basic biology of these unusual organisms, according to Balish.
Characterizing biofilms of M. pneumoniae and understanding how the bacterium interacts with human tissues will contribute to the development of new treatments for pneumonia and other diseases.
Biofilms of M. pneumoniae — a simplified organism that contains only about 700 genes — have not been thoroughly characterized.
Feng and Distelhorst conducted a study to investigate the organization and developmental timeline of M. pneumoniae biofilms.
Using scanning electron microscopy at 5,000 and 20,000 magnification, the researchers found that “despite their genetic simplicity, these bacteria undergo significant changes in appearance during biofilm maturation,” Feng said.
The bacterial biofilms were also treated with a 2-aminoimidazole (2-AI) compound — an emerging class of small molecules, derived from marine sponges, that have the ability to disrupt biofilms formed by many bacteria.
Results showed that the 2-AI compound interfered with growth of M. pneumoniae biofilms, “even though this simplified organism lacks any of the known molecular targets of 2-AIs,” Feng said.
This work not only establishes some of the basics about M. pneumoniae biofilms “but also paves the way for the creation of new treatments for patients infected with this organism,” Feng said. “It may reveal more information about 2-AIs and their potential for combating a wide variety of bacterial infections around the globe.”
Feng, who led the study, received a $500 travel award from the American Society for Microbiology (ASM) to present a poster of her work at the General Meeting of the ASM in New Orleans, May 30-June 2.
Feng’s poster was selected as an Outstanding Student Poster by the ASM, an honor “dedicated to highlighting exceptional students for outstanding research efforts.”
The 2-AI compound was synthesized by Christian Melander, Howard Schaeffer Distinguished Professor of Chemistry, at North Carolina State University. Its use in the Balish lab was facilitated by John Cavanagh, William Neal Reynolds Professor of Biochemistry, also at NCSU.