Center of Excellence in Microbiome Sciences

Maryland has one of the most densely populated areas of commercial poultry in the U.S. that brings an estimated $1.6 billion in economic impact to the state each year.

Protecting this important agricultural resource from infectious disease, including devastating outbreaks of avian mycoplasma and highly pathogenic avian influenza (HPAI), requires vigilance, good science and cooperation between poultry growers, extension agents and policymakers.

At the University of Maryland, one of the region’s top experts in infectious poultry diseases is expanding his scientific toolkit, harnessing the use and application of advanced molecular diagnostic and genotyping techniques for the surveillance, prevention, and control of pathogens like HPAI.

Mostafa Ghanem, an assistant professor of veterinary medicine in the College of Agriculture and Natural Resources, is using these new genomic tools to improve the current understanding of different risk factors controlling the emergence, evolution, spread and persistence of different pathogens within animal production systems and different environments.

He works closely with state diagnostic laboratories, federal agencies, and academic and private industry partners to achieve a common goal of improving the health and wellbeing of animals and humans.

Ghanem is active in the University of Maryland Center of Excellence in Microbiome Sciences, launched in 2023 with a $500K Impact Award from the university’s Grand Challenges Grants program.

—Story by Tom Ventsias, UMIACS communications group

 

The U.S. Food and Drug Administration (FDA) has awarded two University of Maryland researchers a $350,000 grant to advance new treatments for female reproductive system conditions.

In a two-year study, Assistant Professor Hannah Zierden and Professor and Chair Peter Kofinas, both of the Department of Chemical and Biological Engineering, will collaborate with the FDA Centers of Excellence in Regulatory Science and Innovation to explore the potential of absorbable polymer devices to prevent intrauterine adhesions. The work could lead to technologies to treat endometriosis, which impacts over 10% of reproductive-age women, causing chronic pain and sometimes leading to infertility, as well as other women’s health issues.

Post-surgical inflammation can lead to tissue adhesions, when organ surfaces stick to each other, potentially evolving into a life-threatening condition. Available treatments, including polymer-based devices, are often ineffective.

“Many of the existing regulatory science tools fail to focus on how novel medical devices will interact in the female body,” said Zierden, a member of the UMD Center of Excellence in Microbiome Sciences. “By examining polymer degradation in the context of female reproductive tract tissues and hormones, our work will establish important benchmarks for the translation of absorbable polymer devices for use in gynecologic and obstetric surgeries, with the potential to address existing disparities in women’s health.”

Zierden is an expert in nanotherapies, a type of medical treatment that uses tiny particles (nanoparticles) to deliver medicine directly to the cells that need it, while Kofinas is an expert in functional polymers for medical applications; together they will test advanced sprayable polymers in the female reproductive tract to evaluate their safety and biocompatibility.

In addition to endometriosis, the work could benefit those experiencing uterine fibroids and gynecologic cancer, among other conditions, as well as patients undergoing gender confirmation surgeries, hysterectomies, myomectomy and other procedures.

“This is a significant milestone in our efforts to address critical gaps in women’s health care,” Kofinas said. “Our work will focus on creating polymer devices that are safe, effective and tailored to the unique physiological conditions of the female reproductive system, ultimately aiming to enhance the quality of life for many women.”

—Story by Daniela Benites, Maryland Today

A University of Maryland expert in computational biology has been awarded significant federal funding to uncover the mysteries of the human gut microbiome.

Brantley Hall, an assistant professor of cell biology and molecular genetics with an appointment in the University of Maryland Institute for Advanced Computer Studies (UMIACS), is the recipient of two awards from the National Institutes of Health (NIH) totaling $3.5 million.

The federal funding—a $1.9 million R35 investigators award from the National Institute of General Medical Sciences and a $1.6 million R33 phased innovation grant from NIH—will support Hall’s groundbreaking work in the characterization of microbial enzymes and the development of novel wearable devices for monitoring gut health.

The gut microbiome is an intricate ecosystem composed of trillions of microorganisms, including bacteria, fungi, parasites and viruses. Each person has their own unique microbiome, which is influenced by their diet and environment. This complexity makes studying gut health considerably challenging for researchers, resulting in a lack of in-depth knowledge about the gut. 

With support from the R35 award over the next five years, Hall and his research team aim to address these challenges, in part by systematically identifying and characterizing a class of microbial enzymes called ene-reductases. These enzymes play a pivotal role in the intricate interactions between gut microbes and their human hosts.

“By discovering key gut microbial enzymes, we aim to uncover how gut microbial biotransformations influence overall human health,” Hall says. 

The R33 grant will provide three years of funding for Hall’s team to develop wearable devices that will enable the real-time monitoring of gut microbial activity. This project aims to translate laboratory findings into practical applications, Hall says, and has the potential to revolutionize the way gut health is measured and managed.

In a broader sense, Hall says this latest round of research funding supports work that will help his team and other scientists highlight the symbiotic relationship between humans and gut microbes. As hosts, we provide our gut microorganisms with shelter and food, and in return, they help us keep our body functioning well, he explains.

These same microorganisms break down dietary fibers and carbohydrates that we can’t digest on our own. They not only affect our digestion, but also interact with a range of organs and systems in our body.

For instance, the gut microbiome affects liver function through the gut-liver axis, a key focus of Hall’s research. A recent study by Hall discovered that our gut microbes’ interactions with liver enzymes is what produces the distinct yellow color of urine. 

While most gut microbes are beneficial, some bacteria can contribute to various health issues. Disorders linked to harmful microbial activity include Inflammatory Bowel Disease (IBD), which affects millions globally. Certain gut bacteria can even produce compounds that elevate risk factors for heart disease, highlighting the broad impact of the microbiome on overall health.

Hall’s research offers significant insights into understanding gut-related disorders and advancing effective treatments. However, the journey toward these breakthroughs has been marked by considerable challenges.

“Gut microbes are really hard to grow,” Hall explains. Although his team uses an anerobic chamber, an environment in which conditions like temperature and oxygen can be carefully controlled, cultivating these enzymes is an incredibly difficult task.

“Identifying the right enzyme among millions of genes is like searching for a needle in a genomic haystack,” Hall says. He and his team use a complex mix of bioinformatics and biochemistry to identify which enzymes are involved in what reactions.  

Given the complex nature of gut microbiome research, providing institutional support to researchers is essential, Hall says.

At the University of Maryland Center for Excellence in Microbiome Sciences, where Hall is an active member, he works with researchers from a diverse range of disciplines, including food safety and nutrition, computer science, bioengineering, civil and environmental engineering, and more. 

He also acknowledges the support from UMIACS, which provides technical and administrative services and is home to the Center for Bioinformatics and Computational Biology, which offers additional computational resources.

“I am deeply thankful to the NIH for their continued investment in microbiome research and to the centers and institutes at the University of Maryland that provide the resources and collaborative environment essential to the success of these projects,” Hall says.

—Story by Aleena Haroon, UMIACS communications group

Leafy greens like spinach and lettuce are among the most nutrient-packed foods we can eat—and some of the most prone to make us miserable, or worse. The pathogenic bacterium Escherichia coli O157:H7 causes millions of illnesses globally each year, health authorities say, including thousands of severe infections that can lead to kidney failure and even death. The infections are often contracted from contaminated produce irrigated with water that contains animal waste runoff or grown in open fields where intruding wildlife leave feces.

To help address this challenge, a University of Maryland food safety expert is conducting microbial research to determine best practices for commercial growers who find evidence of wildlife feces, or scat, in their fields.

Shirley Micallef, a professor in the Department of Plant Science and Landscape Architecture, recently concluded a series of field trials on Maryland’s Eastern Shore that examined how E. coli moves from scat to a lettuce crop following a rain event.

Micallef aims to determine a specific safety radius for a “no harvest” zone if farmers find evidence of wildlife intrusion, data that will be useful for mid-Atlantic produce growers and the U.S. Food and Drug Administration. Due to variance of wildlife, soil composition, farming scale and climate, the data and metrics in place for California may not be suited for Maryland, Micallef said.

The results from the research, which involved other faculty and students in the College of Agriculture and Natural Resources, were recently published in the journal Frontiers in Plant Science.

This project, Micallef said, is part of the work she does in the University of Maryland Center of Excellence in Microbiome Sciences, launched last year with a $500K Impact Award from the university’s Grand Challenges Grants program.

“This matches well with the center’s goal of research, education and outreach that is focused on the concept of ‘One Health’—wherein interconnected microbiomes affect the health and well-being of plants, the environment, animals and humans equally,” Micallef said. “They all interact with each other at some level.”

-Story by Tom Ventsias, UMIACS communications group

 

 

You could say that a gut feeling guided Brantley Hall’s career path.

After earning his Ph.D. in genetics, bioinformatics and computational biology from Virginia Tech in 2016, Hall began studying something that’s part of every person on the planet: the gut microbiome. Trillions of microorganisms form communities in the gastrointestinal tract that are vital to human health, but much is still unknown about their intricacies.

Now an assistant professor of cell biology and molecular genetics with a joint appointment in the University of Maryland Institute for Advanced Computer Studies (UMIACS), Hall works to demystify the process of digestion.

“I’m extremely happy to have chosen this field,” said Hall, who is a core faculty member in both the Center for Bioinformatics and Computational Biology and University of Maryland Center of Excellence in Microbiome Sciences. 

“It’s rewarding because so many people can relate to and engage with my research. Even your choice of lunch has a huge impact on your gut microbiome.”

Hall’s lab studies the human gut microbiome and its links to medical ailments such as inflammatory bowel disease. His team developed a wearable device that measures gas produced by gut microbes—a tool that, until now, never existed. By taking these measurements in real time, Hall hopes to shed light on a range of gastrointestinal symptoms that can hamper a person’s quality of life.

Gut microbiome research has a wide range of applications in medicine. A recent study led by Hall identified the gut microbial enzyme responsible for making urine yellow.

“This enzyme discovery finally unravels the mystery behind urine’s yellow color,” Hall said. “It’s remarkable that an everyday biological phenomenon went unexplained for so long, and our team is excited to be able to explain it.”

Hall and his collaborators believe this enzyme, called bilirubin reductase, could be linked to jaundice—a condition that leads to yellowing of the skin and eyes—and plan to do a clinical trial in infants to test their hypothesis.

The gut microbiome also shares links with allergies, diabetes, arthritis, multiple sclerosis, psoriasis, Parkinson’s disease and many more conditions. Despite its importance to human health, gut microbiome research is still in its infancy. It didn’t take off until the early 2000s, with the rise of genomic sequencing and oxygen-free chambers that allowed microbes to be grown in a lab.

“Scientists have known about the importance of the gut microbiome for a long time, but there was just no one way to grow or measure the microbes,” Hall said. “We knew stuff was happening in people’s guts and that microbes were responsible, but beyond that, there wasn’t much we could do.”

While Hall’s lab grows and studies microbes in isolation, his team aims to tackle a bigger challenge: figuring out how to study the activity of microbial communities in a live human body.

“We need to measure what microbes are doing in real time—that’s the big gap in the field,” Hall said. “What we need are new tools that can measure gut microbes.”

Looking back at the last seven years, Hall is glad he followed his gut and pursued this field of research. He said gut microbiome research holds enormous potential for improving people’s health and well-being—and researchers are just getting started.

“I love it,” Hall said. “It’s a great field, and I feel like we’re working toward something that is going to make a difference.”

—This story was originally published by the University of Maryland Department of Cell Biology & Molecular Genetics

Hannah Zierden, an assistant professor in the Department of Chemical and Biomolecular Engineering, was named the Maryland Academy of Sciences’ Outstanding Young Engineer for her advancements towards specialized nanotechnologies for female reproductive health.

Zierden’s distinction comes from her commitment to one of the most pressing and underserved fields of human medicine, where disparities in funding resources and specialized clinical trials have historically slowed new avenues to enhance women’s health. She followed the footsteps of her graduate mentor, Laura Ensign, and became the second in the department to earn this recognition.

“Many of the Maryland Academy of Sciences awardees are researchers whose work I admire and respect. I am honored to be among them, and have big shoes to fill. I hope to inspire the next generation of engineers and scientists in the coming decades,” said Zierden.

Her pioneering work in therapies for gynecological patients began as a graduate student at Johns Hopkins University, where, after identifying inconsistencies with established models, she developed an animal model to mimic inflammation-induced preterm birth. Her work established an important tool to observe uterine contraction mechanisms via rodents, which resulted in a first-author publication in the American Journal of Pathology, and a Career Development Travel Award from the National Institutes of Health to present her discovery in the Society for Reproductive Investigation Annual Meeting in 2019.

Using this model, Zierden engineered a novel combination nanotherapy for preterm birth prevention. Her work was the first reported evidence of success in preclinical trials for a condition with no treatment approved by the U.S. Food and Drug Administration. This groundbreaking work led to two publications in Science Translational Medicine and Frontiers in Cellular and Infection Microbiology during her graduate studies.

In her short time at Maryland, she has earned affiliations with the university’s Fischell Department of Bioengineering, the Robert E. Fischell Institute for Biomedical Devices, and the Center of Excellence in Microbiome Sciences. Looking ahead, her work seeks to understand how cells communicate in order to shy away from traditional synthetic drugs—developing biological treatments for gynecological patients that may suffer from infertility conditions, bacterial vaginosis, preterm birth and pelvic inflammatory disease, among others. She aims to bridge the gap in specialized treatments for the female reproductive tract for the generations to come.

“As a woman and a mother of a daughter, I hope that women’s health in the coming decades isn’t at a significant disparity when compared to other medical implications. I am working to make sure that my daughter’s reproductive health won’t suffer from a lack of treatment options,” she said.

—This article was originally published by the UMD Clark School of Engineering

E.coli bacteria and an electronic device might seem to have little in common, but in a recent experiment, University of Maryland researchers linked them into the first closed-loop system able to communicate across the technological-biological divide.

A team from the Robert E. Fischell Institute for Biomedical Devices and the Institute of Bioscience and Biotechnology Research (IBBR) used chemical reactions and genetic engineering to demonstrate how electronic signals can control the biological processes of cells in real time in a paper recently published in Nature Communications.

The research—led by bioengineering Professor and Fischell Institute Director William E. Bentley and IBBR Research Professor and Fischell Institute Fellow Gregory F. Payne—could be the first step toward developing translatable “smart” health care devices, such as drug-delivery systems for diabetics or real-time trackers of disease progression in cancer patients. (E. coli was chosen because it is an easy-to-propagate microorganism frequently used in experiments.)

The two researchers have been working jointly to advance bioelectronics for years. They say that while devices such as defibrillators and electrocardiograms, which work with electrical signals from the heart, mark great advancements in bioelectronics, there remains a gap in simple devices that access molecular information for health metrics and disease treatment—a gap that their recent progress may begin to address.

“A longstanding impediment to commercialized bioelectronics technology is the ability to successfully establish a seamless connection between biological systems and electronic devices,” said Bentley, who is also a member of UMD’s Center of Excellence in Microbiome Sciences. “As with so many complex relationships, the core of the solution requires good communication—the successful exchange of information.”

In conventional electronics, a flow of electrons through wiring and circuitry carries information, while electromagnetic waves do the work in wireless communications.

“In biology, there aren’t free electrons moving through your body,” said Sally Wang Ph.D. ’23, a postdoctoral researcher and co-lead author on this paper with Chen-Yu Chen Ph.D. ’23, a fellow researcher in Bentley’s lab. “So what do biological systems do to move those electrons? They transfer electrons using redox reactions.”

Cells make redox (or reduction-oxidation) molecules, which can transport electrons from one place to another using redox chemical reactions, causing the gain and loss of electrons in cells. This electron transfer results in changes to oxidation levels in cells and is central to important biological processes like photosynthesis and respiration.

Nearly six years ago, Bentley and Payne demonstrated that redox reactions can bridge the gap between biological and electronic systems; they have since worked to engineer and manipulate biological redox networks for bioelectronic information transfer at multiple levels, including proteins, individual cells and groups of cells. This multifaceted and interwoven connection between systems is what the team has coined the “Internet of Life.”

Building on this research, Wang and Chen demonstrated a closed-loop system where a cell’s biological activity can not only be monitored in real-time using electronic signals, but its genetic systems can also be electronically controlled. The latter function is referred to as “electrogenetics,” an approach that the UMD team introduced and that has since been adopted by several groups worldwide.

Using the gene editing tool CRISPR, the team engineered E. coli bacterial cells to include proteins and antibodies from other organisms such as jellyfish and Pseudomonas bacteria to enable E. coli to respond in a specific way to electricity: When they receive electrons, they project fluorescence as optical signals that can be recorded and interpreted by a machine in real time. The machine can then assess whether it needs to supply more current in order to sustain the transfer of electrons between systems, demonstrating a cycle.

The engineered cells can accept electrons from electrodes as well as from cells via redox reactions, making them in effect “bilingual.”

“This opens doors for building completely new ways to connect information and data-rich technologies to biology,” said Bentley. “There are myriad opportunities that could emerge from electrogenetics.”

In addition to health care innovations—for instance, a self-regulated device connected to the body that monitors a disease and precisely administers drugs—the technology has potential applications in agriculture and environmental conservation as well. A “smart” farmland monitor, for example, could telemetrically provide information about how to optimize the microorganism content in soil, suggesting how much pesticide and herbicide to use and when.

Other authors of this study include Fischell Institute researchers John R. Rzasa, Chen-Yu Tsao, Eric VanArsdale Ph.D.’22 and Fauziah Rahma Zakaria ’25 and IBBR members Jinyang Li Ph.D. ’20 and Eunkyoung Kim.

—This story was originally published by Maryland Today

More than 70 people braved stark wintry conditions on January 16 to attend a research symposium at the University of Maryland that explored the world of complex microbial communities.

The Symposium on Microbiome Research at the Interface of Environment, Health and Agriculture joined researchers from the federal government, academia and private industry who are focused on the connectivity between microbes interacting with each other, the environment, agricultural systems, and human and animal health.

Hosted by the University of Maryland Center of Excellence in Microbiome Sciences, the event featured multiple talks, breakout sessions, an engaging poster session, and a networking reception. All the events went off without a hitch, despite 4 inches of snow that closed the university for the day and made travel difficult.

“We were fortunate that more than two-thirds of the people who registered were able to show up and participate,” says Mihai Pop, a UMD professor of computer science who is the director of the microbiome center. “We were particularly pleased by the strong turnout from federal scientists in the region, as well as colleagues from the medical and dentistry schools in Baltimore.”

A morning keynote talk by Susannah Tringe, division director of the DOE Joint Genome Institute at the Lawrence Berkeley National Laboratory, looked at the sequence-based interrogation of soil microbiomes, and how those microbes can benefit various ecosystems.

The afternoon keynote by Joff Silberg, a professor of biosciences at Rice University, was presented virtually as Silberg was unable to fly out of Houston due to poor weather. His talk explored the use of engineered living microbes, and how they might be used to monitor various soil pollutants in real time.

Other talks included how microbial communities can impact coffee growers, the effect of cow manure microbes on farm soil, microbial activity related to women’s gynecologic health, and other topics focused on human gut bacteria and inflammatory bowel disease.

“There’s such a rich diversity of perspectives and ongoing work at the University of Maryland involving microbiome sciences,” says Hannah Zierden, an assistant professor of chemical and biomolecular engineering at UMD and core member of the microbiome center. “I’m excited at the opportunities we have and look forward to continued collaborations—as well as new ones—as we expand our outreach and impact.”

Zierden presented some recent research from her own UMD lab at the conference, which aims to better understand the function of bacterial extracellular vesicles produced by vaginal microbes, and how they might be used to engineer biocompatible therapies for healthy pregnancies.

A large contingent of researchers from the University of Maryland School of Dentistry were onsite for the symposium, including Areej Alfaifi, a doctoral student in the dental biomedical sciences program.

“This event broadened my perspective by introducing me to entirely different aspects of microbiome studies,” says Alfaifi, whose dissertation explores the use of genomic sequencing tools to gain a deeper understanding of the oral microbiome in COVID-19 patients. “Connecting with students and faculty from different schools was an amazing experience that reshaped my thoughts on the field. This meeting was truly unforgettable!”

Additional attendees included faculty, postdocs and graduate students from the University of Delaware, Towson University, University of Maryland School of Medicine, and the University of Maryland, College Park.

Federal scientists in attendance hailed from the USDA, FDA, Department of Energy, and the Smithsonian National Zoo, with representatives from QIAGEN, CosmosID—both major sponsors of the symposium—also present.

The symposium also received support from the University of Maryland Institute for Advanced Computer Studies, Mid-Atlantic Microbiome Meet-up, and the UMD’s Grand Challenges Grants program.

Pop said the UMD microbiome center will help coordinate another symposium in 2025 in Baltimore, working closely with the Institute for Genome Sciences at the University of Maryland, Baltimore to investigate new topics related to microbiome sciences.

“We expect to continue our momentum in this area, which reaches across multiple scientific, medical and policy-related disciplines,” Pop says. “Our belief is that the basic unresolved questions involving microbial communities are interrelated—and so are the solutions we’re working on.”

—Story by Maria Herd, UMIACS communications group

 

Researchers at the University of Maryland and National Institutes of Health have identified the microbial enzyme responsible for giving urine its yellow hue, according to a new study published in the journal Nature Microbiology on January 3, 2024.

The discovery of this enzyme, called bilirubin reductase, paves the way for further research into the gut microbiome’s role in ailments like jaundice and inflammatory bowel disease.

“This enzyme discovery finally unravels the mystery behind urine’s yellow color,” said the study’s lead author Brantley Hall, an assistant professor in the University of Maryland’s Department of Cell Biology and Molecular Genetics. “It’s remarkable that an everyday biological phenomenon went unexplained for so long, and our team is excited to be able to explain it.”

When red blood cells degrade after their six-month lifespan, a bright orange pigment called bilirubin is produced as a byproduct. Bilirubin is typically secreted into the gut, where it is destined for excretion but can also be partially reabsorbed. Excess reabsorption can lead to a buildup of bilirubin in the blood and can cause jaundice—a condition that leads to the yellowing of the skin and eyes. Once in the gut, the resident flora can convert bilirubin into other molecules.

“Gut microbes encode the enzyme bilirubin reductase that converts bilirubin into a colorless byproduct called urobilinogen,” explained Hall, who has a joint appointment in the University of Maryland Institute for Advanced Computer Studies and is a core faculty member in the Center for Bioinformatics and Computational Biology and Center of Excellence in Microbiome Sciences. “Urobilinogen then spontaneously degrades into a molecule called urobilin, which is responsible for the yellow color we are all familiar with.”

Urobilin has long been linked to urine’s yellow hue, but the research team’s discovery of the enzyme responsible answers a question that has eluded scientists for over a century.

Aside from solving a scientific mystery, these findings could have important health implications. The research team found that bilirubin reductase is present in almost all healthy adults but is often missing from newborns and individuals with inflammatory bowel disease. They hypothesize that the absence of bilirubin reductase may contribute to infant jaundice and the formation of pigmented gallstones.

“Now that we’ve identified this enzyme, we can start investigating how the bacteria in our gut impact circulating bilirubin levels and related health conditions like jaundice,” said study co-author and NIH Investigator Xiaofang Jiang. “This discovery lays the foundation for understanding the gut-liver axis.”

In addition to jaundice and inflammatory bowel disease, the gut microbiome has been linked to various diseases and conditions, from allergies to arthritis to psoriasis. This latest discovery brings researchers closer to achieving a holistic understanding of the gut microbiome’s role in human health.

“The multidisciplinary approach we were able to implement—thanks to the collaboration between our labs—was key to solving the physiological puzzle of why our urine appears yellow,” Hall said. “It’s the culmination of many years of work by our team and highlights yet another reason why our gut microbiome is so vital to human health.”

The scientific finding has garnered national media attention from CBS News, the Washingtonian, and WTOP News.

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This article was adapted from text provided by Brantley Hall and Sophia Levy.

In addition to Hall, UMD-affiliated co-authors included Stephenie Abeysinghe (B.S. ’23, public health science); Domenick Braccia (Ph.D. ’22, biological sciences); biological sciences major Maggie Grant; biochemistry Ph.D. student Conor Jenkins; biological sciences Ph.D. students Gabriela Arp (B.S. ’19, public health science; B.A. ’19, Spanish language), Madison Jermain, Sophia Levy (B.S. ’19, chemical engineering; B.S. ’19, biological sciences) and Chih Hao Wu (B.S. ’21, biological sciences); Glory Minabou Ndjite (B.S. ’22, public health science); and Ashley Weiss (B.S. ’22, biological sciences).

Their paper, “Discovery of a gut microbial enzyme that reduces bilirubin to urobilinogen,” was published in the journal Nature Microbiology on January 3, 2024.

This research was supported by the NIH’s Intramural Research Program, the National Library of Medicine and startup funding from UMD. This article does not necessarily reflect the views of these organizations.