Center of Excellence in Microbiome Sciences

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.