Date January 16, 2025
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Searching for cures for antibiotic resistance on the road to scientific and personal discovery

In an intensive Winter Session course at Brown, undergraduates learned lab techniques and performed experiments as they sought breakthrough discoveries to inform future antibiotic treatments.

PROVIDENCE, R.I. [Brown University] — On an early-January afternoon in a large Brown University Biomedical Center laboratory, scientists are analyzing water samples for bacteria that could be used in antibiotics to treat infectious disease. Each is wearing a white coat and focusing intently on a test tube as they perform gel electrophoresis, a process that allows them to separate the DNA in their samples by pushing it past an electrical field and through a gel that contains small pores. Despite the technical complexity of the endeavor, this marks the first time that some of the scientists have conducted research in a lab.

That’s because the scientists are Brown undergraduates enrolled in an immersive course called Antibiotic Drug Discovery: Identifying Novel Soil Microbes to Combat Antibiotic Resistance. The class runs for four weeks during Winter Session, an intensive and often-intense academic term between Brown’s fall and spring semesters. 

Antibiotic resistance is a major global health threat, explained Toni-Marie Achilli, a senior lecturer in biology who developed and teaches the course. Pharmaceutical companies are less likely to fund research and development for new antibiotics due to their relative low profitability, Achilli said — yet as bacteria become more resistant to antibiotics, a robust pipeline of new drug options is needed to combat pathogens. 

And that’s precisely the need the students in the class are helping to address, as they participate with a global research consortium in the quest to discover life-saving new drugs.

Antibiotic Drug Discovery is an example of Brown’s course-based undergraduate research experiences (CUREs), which are designed to provide students the opportunity to engage in research experiences that cultivate their investigative skills, sense of discovery and interest in STEM and social science fields. 

“The course provides a really authentic type of research experience,” Achilli said. “The students are asking novel questions, and they’re developing the scientific skills of designing experiments and the technical skills of performing laboratory techniques to explore those questions. This course can be an incredible springboard for them, if they do want to continue pursuing research. And it’s an equally valuable opportunity for those who want to give research a try if only to learn that it’s not for them.” 

Many of the students who take the course end up pursuing research at Brown and beyond. Achilli recalled one participant who in 2021 discovered a new type of chromobacterium. Nikolas Montaquila took the initiative to find a collaborator from Midwestern University to learn about the chromobacterium, then brought the project back to Brown and developed an independent study with Dr. Gerard Nau, an associate professor of medicine and clinician educator at the Warren Alpert Medical School and an infectious diseases physician at the nearby Rhode Island and Miriam hospitals. The student is now in his first year of medical school at Brown, and the project is ongoing.

“Not only did Nikolas continue conducting scientific research, in general, but he was able to continue the research on what he found in this class,” Achilli said. “In fact, Dr. Nau just reached out to me this month, asking if he could add an assay from his lab to this Winter Session class to try to find more isolates for his lab to continue studying.”

The hybrid course began in late December, before the holidays — the students met online, learned about the global health crisis of antibiotic resistance, explored various scientific techniques available to them, and developed their research question and hypothesis.

While previous classes had analyzed soil, this cohort focused on water. Their professor and two teaching assistants prepared 16 test samples, which consisted of water collected from rural and urban ponds, rivers and puddles in Rhode Island, Massachusetts and Connecticut.

Most antibiotics used in medicine today are molecules produced by soil bacteria and fungi, used as a defense mechanism to promote their own survival, Achilli explained. The students were participating in a global antibiotic discovery effort organized by the Tiny Earth Network based at the University of Wisconsin and involving student researchers at over 540 institutions. 

Over three weeks, the students would culture and grow bacteria from the samples, isolate the different strains, extract DNA from the bacteria and send it to an external lab to be analyzed. Next, students would design an experiment to see if their newly discovered bacteria had antibiotic activity against "safe-relatives" of pathogens that are resistant to common antibiotics. The strains that that did would be analyzed using biochemical techniques to extract the molecules with antibiotic activity. 

The students worked in the lab every weekday, learning to properly perform the techniques of polymerase chain reaction (PCR), gel electrophoresis and DNA sequencing. 

“I tell the students that they really get to do everything, including microbiology, molecular biology, bioinformatics — when the samples come back from the external lab — and even organic chemistry, which they’re doing as they extract metabolites from the samples,” Achilli said.

Scientific and personal discovery

The bacteria on the lab plates looked like art projects: smears of different colors on clear disks. Hattie Grant, a senior concentrating in neurobiology, had missed class due to illness when it was time to choose a plate, so she ended up with one that had only white streaks — surely a disappointing sign of a lack of diversity in the sample, everyone assumed — but it ended up that the sample had a highly promising and active bacterial isolate.

Grant enrolled in the class both to fulfill a research requirement and because she had taken a class with Achilli before and looked forward to learning with her in a course that promised an abundance of hands-on activity. Grant said she appreciated learning about scientific techniques, like working with bacteria and performing PCR and gel electrophoresis.

“Now I feel like I can perform these techniques on my own, with success,” Grant said. “It’s a really nice feeling.”

She also valued being part of a community of scientists: being able to connect with fellow students, work independently yet also as part of a small group, and having the direct support of the professor, teaching assistants and staff laboratory technicians. The technicians had come to the Biomedical Center over the holidays to set up equipment and prepare the work stations, and they regularly attended the lab sessions. The course would not be possible without their knowledge, dedication and skills, Achilli said.

On a recent Friday in January, the students were assigned to perform PCR, which is used in molecular biology to amplify small sections of DNA or a gene. They also needed to conduct what’s called PCR cleanup to purify the DNA and remove extra unwanted components, like enzymes, nucleotides, primers and buffer components. Three Brown lab technicians were on hand to instruct students on how to use the lab equipment, share best practices and answer questions.

Kelly Cleveland, a lab technician and teaching associate in Brown’s Division of Biology and Medicine, demonstrated how to use a brand-new NanoDrop device and provided feedback to the first-time users.

“I can’t believe you’ve never done this before, because that is some expert pipette-ing,” Cleveland told one student as he confidently flicked the end of a pipette into a waste bucket. 

While answering questions from another group of students, Cleveland addressed one of their concerns. 

“That just means that your PCR was super effective, and your PCR cleanup was really good, too,” she said reassuringly. The students cheered in response.

Over the last few days of the Winter Session course, before the spring semester starts, participants will prepare a poster presentation and discuss their findings with fellow student-scientists. 

Achilli said that while many participants have discovered promising bacterial isolates, it’s rare to find a new viable antibiotic; in her six years teaching this course, only one student has done so. But in the process, the students are making other key discoveries, such as sparking an interest in scientific research and developing a sense of confidence in a laboratory setting. 

Olamide Olofin, a senior concentrating in health and human biology who is interested in learning more about antibiotic resistance, said the class had exceeded even her high expectations. 

“I love how hands-on it is, and how independent we are,” Olofin said. “We’re able to explore our own research questions, do our own research, without too much hand-holding or judgment. We really are doing it ourselves.”

Olofin said that based her positive experience, she has decided to pursue an opportunity during a gap year that will allow her to conduct similar research and use some of the techniques she’d learned during Winter Session. 

Brown senior Ndayiragije Anitha enrolled in the course because she wanted the lab experience that is a pre-requisite for her computational biology concentration. After taking a genetics class last semester in which she learned some of the same techniques, Anitha said she had been intrigued and wanted to take that learning even further. As the Winter Session course was wrapping up, she said she appreciated the sense of autonomy Achilli had fostered among the students in the lab. 

“I loved getting to design our own experiments,” Anitha said. “I also liked being able to do the lab techniques completely by ourselves. It’s so good to know that I can now perform all of these techniques on my own. I can do my own research!”