Deadly gas, hidden fuel: NSF award backs probe of microbial carbon monoxide sensing

Carbon monoxide occupies a peculiar position in the human imagination. It is the silent killer, the odorless gas that seeps from faulty furnaces and exhaust pipes, binding to hemoglobin with an affinity roughly two hundred times greater than oxygen and quietly starving tissues of the air they need. Yet in the microbial world, the very same molecule tells a radically different story. For countless bacteria living in soils, sediments, and the deep ocean, carbon monoxide is not a poison but a resource, a signaling molecule, and in some cases a primary source of cellular energy. Understanding how living cells distinguish between these two faces of one of chemistry’s simplest molecules is now the focus of a major new research program at Wayne State University in Detroit.

Dr. Matthew R. Dent, an assistant professor of chemistry in Wayne State’s College of Liberal Arts and Sciences, has received a Faculty Early Career Development (CAREER) award from the U.S. National Science Foundation, one of the agency’s most competitive honors for early-career researchers. The five-year, $749,702 grant supports a project titled “CAREER: Carbon Monoxide Sensing, Selectivity, and Signaling in Microbes.” The award is designed to integrate research with education and public engagement, and Dent’s plan does exactly that, pairing laboratory investigation of gas-sensing proteins with training for students and hands-on outreach to the Detroit community.

The scientific premise of the project rests on a striking paradox. Carbon monoxide is not merely an industrial pollutant or a household hazard; it is produced naturally inside nearly all living organisms, including humans. In mammalian biology, it is generated during the breakdown of heme by heme oxygenase enzymes and plays documented roles in regulating cellular growth, cell death, and inflammation. Researchers have long suspected that this endogenous gas could be harnessed for novel human therapeutics, perhaps as a modulator of immune responses or a protector of transplanted tissue. At the same time, certain bacteria can literally “eat” carbon monoxide, oxidizing it and channeling the electrons into their metabolism as an alternative fuel when more conventional nutrients are scarce. That dual identity, therapeutic agent and microbial food, makes carbon monoxide one of the most intriguing small molecules in biology.

What makes the situation scientifically urgent is how little is actually known about the detection side of the equation. Despite decades of work on carbon monoxide’s chemistry and toxicity, researchers still have a surprisingly incomplete picture of how biological systems sense the gas and convert that detection into concrete cellular actions. How does a bacterium know carbon monoxide is present? How does it distinguish carbon monoxide from the chemically similar gases that surround it, such as oxygen and nitric oxide? And how does a molecular encounter with a diatomic gas translate into changes in gene expression that reshape the cell’s behavior? These are the questions Dent’s laboratory is built to answer.

The experimental strategy centers on microbial transcription factors, the proteins that control gene expression by binding to DNA and switching genes on or off. In carbon monoxide-responsive transcription factors, the gas is recognized through specialized metal ion sites, most commonly an iron atom held within the protein in a heme-like coordination environment. When carbon monoxide binds to that metal center, it changes the geometry and electronic state of the complex, and that change propagates through the protein’s structure to alter its interaction with DNA. The result is a direct molecular line of communication between the gas in the environment and the genome of the cell. Because these proteins bind carbon monoxide tightly and selectively, they serve as powerful and experimentally accessible models for studying gas signaling in general.

Dent’s team will pursue this problem by integrating several complementary techniques. Protein biochemistry will reveal how the sensor proteins behave in isolation and how their DNA-binding properties shift when carbon monoxide is present. Cell biology experiments will connect those molecular events to observable changes in living microorganisms. Genomic approaches will allow the researchers to scan across diverse microbial species and identify previously unknown carbon monoxide-sensing proteins, expanding the known roster of these molecular detectors far beyond the handful of well-characterized examples. Finally, bioinorganic spectroscopy will probe the metal centers themselves, determining the structural blueprints that allow a protein to grab carbon monoxide while ignoring the chemically related gases that could otherwise trigger false signals. Together, these approaches promise a comprehensive picture of gas sensing at the atomic level.

The potential applications extend well beyond basic microbiology. If researchers can define the rules that govern selective gas recognition in proteins, those rules could inform the design of new biosensors capable of detecting carbon monoxide or other gases with high precision, with uses ranging from environmental monitoring to medical diagnostics. The same knowledge could guide the development of carbon monoxide-releasing molecules as therapeutic agents, where controlled delivery of the gas could exploit its anti-inflammatory and cytoprotective effects. And because some microbes can grow on carbon monoxide as a fuel, a deeper understanding of the underlying biology could contribute to alternative bioenergy strategies that convert waste gases into useful products. “Carbon monoxide has a notorious reputation as a poison, but in biology, it is also a powerful signal and an energy currency for certain microbes,” Dent said in the university’s announcement. “By studying how microbes selectively identify CO at the molecular level, we can learn how living cells harness this gas. These fundamental discoveries could open exciting doors for designing new medical treatments, developing biosensors and advancing alternative bioenergy strategies.”

The education and outreach component of the CAREER award is woven into the research program rather than bolted on. Dent’s project will train both undergraduate and graduate students in STEM fields, giving them experience not only in laboratory research but also in science communication, a skill increasingly recognized as essential for scientists working on topics, like gas toxicity and blood chemistry, that intersect directly with public health. The outreach arm of the project takes the form of a hands-on community program exploring the biochemistry of blood, connecting the molecular story of carbon monoxide, hemoglobin, and oxygen transport to concepts people encounter in everyday life. The program is designed to make the invisible chemistry of the bloodstream tangible and to draw community members into a conversation about science that affects their health.

That outreach effort has already been tested in the field. In a partnership with Wayne State University Athletics, Dent and his team piloted the program earlier this year at the Fourth Annual I-96 Blood Battle, a blood drive competition between Wayne State and Davenport University. The event proved a fitting venue for a project rooted in the chemistry of blood, and it delivered a decisive result for the home team: the Wayne State Warriors secured twice as many blood donations as the Davenport Panthers, winning the competition soundly. Dent has indicated that he looks forward to continuing the community partnership in the coming years, using the blood drive as a recurring platform for the outreach program.

Leadership at Wayne State has framed the award as emblematic of the university’s broader research ambitions. “Dr. Dent’s groundbreaking investigation is an excellent example of the caliber of pioneering research taking place across Wayne State University’s campus,” said Dr. Ezemenari M. Obasi, vice president for research and innovation. “By bridging chemistry with future applications in human health, environmental sustainability and community-engaged STEM education, this project reflects our commitment to translating research that will impact our community and beyond.” The CAREER program, which funds the project under grant number 2540612, specifically recognizes early-career faculty with the potential to serve as academic role models and to lead advances in their institutions’ missions. For a molecule long defined by its dangers, the award marks a shift in perspective: carbon monoxide as a key to understanding how life senses, signals, and survives, investigated from a laboratory in Detroit with results that could ripple outward into medicine, energy, and the education of the next generation of scientists.

Subject of Research: Microbial carbon monoxide sensing, selectivity, and signaling by gas-binding transcription factor proteins

Article Title: From silent killer to cellular fuel: Wayne State chemist unlocks nature’s carbon monoxide sensors

Article References: From silent killer to cellular fuel: Wayne State chemist unlocks nature’s carbon monoxide sensors. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: carbon monoxide, NSF CAREER award, Wayne State University, microbiology, transcription factors, gas sensing, bioinorganic chemistry, heme proteins, biosensors, bioenergy, science outreach, gene expression