The whole Pharmaceutical Discovery from Cyanobacteria group out in the field. Photo: Ashu Tripathi.

The word “medicine” conjures up images of white coats, sterile offices, and orange bottles full of pills. But where does this medicine come from? It turns out the neat-and-tidy final products often obscure a less manicured origin.

A large proportion of medicine - compounds with antibacterial, anticancer, and insecticidal properties - is derived from naturally occurring molecules in the environment. In fact, up to 50% of drugs approved in the last 30 years originate from natural products (Newman and Cragg, 2012), and cyanobacteria are particularly renowned for producing therapeutically-relevant compounds.

Enter: Dr. David Sherman, U-M Research Professor in the Life Sciences Institute, College of Pharmacy, Medical School, and College of Literature, Science, and the Arts. He and his research group study the biosynthesis of natural products from microbes, including cyanobacteria. In collaboration with colleagues Dr. Ashootosh Tripathi, Director, UM Natural Products Discovery Core, Research Assistant Professor of Medicinal Chemistry; Dr. Amy Fraley; Dr. Andrew Robertson, and UMBS Transforming Learning Program (TLP) coordinator Alicia Farmer, he dreamed up an undergraduate course in which students get to participate in the entire process of drug development, from environmental collection, to laboratory extraction, analysis, and eventual application. The research infrastructure - plus extensive wetlands, inland waterways, and Great Lakes surrounding UMBS - seemed the perfect headquarters.

Undergraduate Allyson Li checks PH in a water sample. Photo: Ashu Tripathi.

This summer, Sherman’s vision became a reality through the new Pharmaceutical Discovery from Cyanobacteria course at UMBS. As part of TLP, the two-week extension is tied to a full-term fall course on campus. Tripathi, Fraley, and Robertson designed the curriculum and led the course, in close collaboration with UMBS Algae in Freshwater Ecosystems professors Dr. Rex Lowe and Dr. Pat Kociolek.

“The purpose of the class is to disseminate information about natural products and introduce undergraduates to this kind of science as a possible career choice,” says Tripathi. “Exploring the biological and chemical diversity of northern Michigan and having access to biology and ecology experts like Rex and Pat are huge draws.”

In the combination field-lab research course, students learn taxonomic identification of biologically relevant blue-green algae (cyanobacteria) and proper field collection techniques. They then head to the lab with samples for extraction and purification of natural products, which are tested for therapeutic properties.

Says Fraley, a Sherman Lab researcher who recently defended her doctoral dissertation: “My experiences in the field changed the way I think about science. It’s enormously valuable to give undergraduates the same opportunity.”

Untapped potential in northern Michigan...

The advantages of hosting the field extension at UMBS are plentiful. In addition to the expertise of resident phycologists and a state-of-the-art analytical chemistry lab, the biodiversity surrounding the Station is unusually rich.

“Within a 70 mile radius, we have access to an astounding array of habitats, organisms, and chemical diversity. Some of the aquatic systems we’re sampling from are relatively uncharted. The possibilities are endless,” says Tripathi.

In the inaugural field course, the instructors and four intrepid students collected samples from a dizzying array of aquatic systems: Wildwood Lake, Osmond Lake, White Lake, Lost Lake, French Farm Lake, the Maple River and former dam site of Lake Kathleen, Lake Michigan, Lake Huron, and of course, Douglas Lake (home of UMBS).

A rainbow array of extractions in the UMBS Chemistry Lab. Photo: Ashu Tripathi.

...And unexpected success!

After testing four initial cyanobacterial extracts, the teaching team and students were astounded to have found antibiotic activity in the Wildwood sample.

Robertson, a postdoc in the Sherman Lab and UM NPDC, could not hide his enthusiasm. “We came prepared that we might not find antibiotic activity, but could plan on sending samples out for anti-cancer testing. Out of only four samples tested, we found one with antibiotic activity - that’s a 25% success rate!”

The results of a Liquid Chromatography–Mass Spectrometry (LC-MS) analysis on blue-green algae from the Maple River. At least three of the blips on the radar are able to kill E. coli and will be further tested in the Sherman Lab.

Tim Veverica, UMBS Analytical Chemist, matched Robertson’s excitement. He passed along imagery from the Liquid Chromatography–Mass Spectrometry (LC-MS) analysis to illustrate the potential.

“This is a run, containing all of the positive-ion molecules from an extract of Maple River blue-greens. At least three of these little "stars" in the galaxy pictured are able to kill E. coli and will be further tested in the Sherman Lab against other pathogens and cancer cell lines.”

“It's pretty wild that students are able to do stuff like this at the end of the road in the woods,” he added.

Better yet: since the class continues into the fall, there is ample opportunity to analyze further samples for bioactive agents.

“Even if we didn’t find anything, we could still look for new molecules and send samples to test for various biological implications,” says Tripathi. “It wouldn’t have deterred us - we’re just scratching the surface. Chemical diversity itself is a valuable discovery. With new chemical entities, there are new biological functions associated. The fact that we found antibiotic activity is a bonus.”

Undergraduate Bailee Bell collects algae samples with a smile. Photo: Ashu Tripathi.

The student experience has been just as positive. Four undergraduates, with various levels of experience, interest, and aspirations in the fields of medicine, pharmacy, and environmental studies, ventured up to UMBS for the extension. One student, Allister Ho, took Algae in Freshwater Ecosystems in the summer term before transitioning into Pharmaceutical Discovery from Cyanobacteria.

“Since I was here for Algae, it’s been fun to gain that background knowledge and now explore this new application. [Pharmaceutical Discovery from Cyanobacteria] highlights a different experience - both in the field and the lab,” said Ho.

On the other side of the coin, Bailee Bell, who works in the Natural Products lab on campus, appreciated the field-based supplement to her analytical experience.

“It’s been good to get to do the sampling in the field and see where everything comes from. The processing takes on a new gravity after seeing everything first hand.”

Allyson Li and John Huynh both commended UMBS’s infrastructure in providing a launchpad for successful learning. For Li, the analytical chemistry lab impressed her just as much as the natural bounty of surrounding environs.

For Huynh, the living-learning community culture of UMBS took the cake.

“I like working alongside my teachers so closely, through thick and thin. I think being in this environment helps foster relationships that you just can’t achieve on central campus.”

As for Tripathi, he is already looking forward to the future. “Next year, we’ll be able to resample our core sites and check for changes in chemical diversity. Hopefully, we can also sample new sites, adding to a multi-year inventory of what’s out there, and how it’s changing.”