The transformative power of a Brandeis education extends into the world of enzymology, as demonstrated by Dr. Mo Seyedsayamdost ’01, whose groundbreaking research is uncovering potentially lifesaving antibiotics. Before earning his PhD at the Massachusetts Institute of Technology, Seyedsayamdost embarked on his journey of scientific discovery at Brandeis University, where he immersed himself in research under the mentorship of Prof. Liz Hedstrom (BIO/CHEM).

In a March 5 exchange with The Justice, Seyedsayamdost reflected on his formative years in Hedstrom’s laboratory, where he worked for a year and a half and co-authored several publications as an undergraduate. He credited Hedstrom’s intellectual precision and insatiable curiosity as profound inspirations. “I was inspired by her rigor as well as her inquisitive mindset,” he shared. In a separate interview with Brandeis Magazine, he painted a vivid picture of his dedication, recalling, “I would do my homework in Hedstrom’s lab … I would eat there. I would do experiments there. It was a refuge, just such a beautiful world in and of itself.”

Beyond his work with Hedstrom, Seyedsayamdost found inspiration in other esteemed members of the Brandeis science faculty. He highlighted former Professor Melissa Moore (BIOL), a key contributor to the development of the Moderna COVID-19 vaccine, and Prof. Daniel Oprian (BIO) as influential figures in his academic path. Moore’s Introduction to Biochemistry course “unlocked my passion for the subject; it made me switch from a pre-med track to research in biochemistry,” he explained.

Seyedsayamdost thrived within Brandeis’ Biochemistry department, describing it as “a mecca for enzymology, and an analytical and deep mechanistic mindset, which was a foundation of the biochemistry department, is something I learned and applied throughout my scientific work.” Today, he serves as a professor of chemistry and molecular biology at Princeton University, where he also mentors students and leads pioneering research in antibiotic discovery.

The majority of commercial antibiotics — used to treat infections ranging from pneumonia to syphilis — originate from molecules produced by a handful of microbial genera. To date, only a few hundred such molecules have been identified. However, microbial life is capable of generating thousands more molecules, most of which remain unexplored.

Seyedsayamdost’s lab is at the forefront of efforts to uncover these elusive antibiotics, an endeavor that has become increasingly urgent due to the alarming rise of antibiotic-resistant bacteria. Over the past two decades, common microbial strains have developed immunity to widely used drugs, complicating treatment efforts. According to the Centers for Disease Control and Prevention, antibiotic-resistant infections afflict approximately 2.9 million people annually in the United States, leading to at least 48,000 deaths.

His lab operates at the cutting edge of antibiotic discovery, leveraging the remarkable efficiency of naturally occurring molecules. Seyedsayamdost explained, “All these traits that chemists work hard to code into synthetic drugs are sometimes just there in naturally produced molecules, because it’s their evolutionary purpose.” Evolution has fine-tuned these molecules over millions of years to perform highly specific biological functions, such as targeting chemical receptors, permeating cell membranes or inhibiting critical enzymes, often with greater efficacy than human-designed compounds.

To harness this potential, Seyedsayamdost’s team has developed an innovative screening methodology known as High-Throughput Elicitor Screening. This approach involves cultivating microbial species on laboratory plates, stimulating them to secrete bioactive compounds and rapidly analyzing the resulting chemical structures and biological properties. The efficacy of this methodology has been remarkable — his team has identified over a thousand novel compounds, a feat that earned Seyedsayamdost a MacArthur “Genius” grant in 2020.

One of his lab’s most promising discoveries emerged in 2023: keratinicyclin B, a molecule produced by certain soil bacteria with the potential to combat Clostridium difficile, a notoriously drug-resistant pathogen. Unlike conventional antibiotics that often disrupt beneficial gut flora, keratinicyclin B selectively targets C. diff. It attacks the cell wall with precision, sparing commensal microbes. This breakthrough holds significant promise for addressing a formidable clinical challenge.

Looking ahead, Seyedsayamdost envisions expanding his research beyond antibiotics to explore other classes of bioactive compounds, including antioxidants, anticancer agents and bacterial signaling molecules. He is particularly interested in harnessing these signaling compounds to manipulate bacterial behavior within the human microbiome. Seyedsayamdost will mobilize beneficial bacteria to preemptively eliminate pathogens before infections take hold. “Harnessing these latter substances … may one day allow us to intentionally control how bacteria in our bodies behave.” Seyedsayamdost speculated further, “maybe in the future, we won’t have to use antibiotics at all … Maybe we can figure out how to trigger our own microbiome to produce these antibiotic molecules themselves.”