Sea Sponge “Library” Enhances Biomedical Research at Dominican

In a Dominican University of California research laboratory containing more than 1,200 species of sea sponges, along with approximately 13,700 vials of sponge-derived crude extracts, researchers are diving into studies focused on how small molecules derived from sponges could slow down the aging process and serve as therapeutic lead compounds to treat cancer, neurobiological disorders, and neglected tropical diseases.

The sea sponge repository was donated to Dominican by distinguished professor of chemistry Phillip Crews from the University of California Santa Cruz (UCSC). The collection dates back to 1973, when Dr. Crews launched a program at UCSC in marine natural products chemistry from local expeditions along the Northern California coastline to examine macroalgae.

"Dominican's sea sponge repository, housed in the Johnson Lab, is the largest west of the Mississippi" says Dr. Tyler Johnson, associate professor in the Department of Natural Sciences and Mathematics.

"Phil built a remarkable program in marine natural products chemistry. He's also been incredibly generous as an educator, collaborator and mentor to so many who studied under or collaborated with him over the years."

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Johnson, who studied under Dr. Crews to obtain his PhD in Chemical Oceanography, participated on a dozen scientific diving expeditions over the past two decades.

"Having organized close to 100 scientific expeditions, Phil is a true pioneer that probed the frontiers of knowledge in marine bioorganic chemistry. We are truly blessed to have the opportunity to continue this tradition of interdisciplinary research," Dr. Johnson says.

The Dominican sea sponge repository is a library of potential new lead compounds just waiting to be unlocked.

"Our research group is now focused on using medicinal chemistry efforts to alter the chemical instability (limited shelf life) or toxicity seen with some of these marine natural products so they can go on to serve as next generation chemical probes or optimized therapeutic lead compounds to treat selected diseases," Dr. Johnson says.

Johnson calls the marine natural products in the sponge repository sit on the shelf compounds, because most of their unique chemical structures have already been solved in the 20th century. However, many of these compounds have never been tested against anything except for cancer cells.

"They're just waiting to be salvaged for repurposing when tested for new biological activities against different disease targets to generate greater rates of scientific discovery," Dr. Johnson says.

Repurposing of compounds from the sea sponge repository has begun to bear fruit. Johnson and six students from his lab recently collaborated with the University of Southern California (USC) discovering a potent and selective new chemical probe to study the aging process that extends lifespan in worms. The study was published the peer review publication GeroScience.

The work showcased how the semi-synthetic sponge-derived compound was not only more stable, but also more selective for cancer versus normal cells compared to the marine natural product.

Other areas of interest to the Johnson lab include neuroscience. In a pilot study, the Johnson Lab collaborated with the Whistler Group at the University of California San Francisco (UCSF) to screen 96 sponge-derived extracts to discover the first marine derived opioid with a signaling profile that resembles the endorphins (the brain's natural pain reliever and anti-depressant). The work was published in the journal ACS Chemical Neuroscience.

Johnson's lab also began a new collaboration with the Rosenthal Lab at UCSF, screening sponge-derived chemotypes to see if they inhibit the malaria parasite P. falciparum. The study found two compounds with potent activity: one on par with the World Health Organization standard anti-malarial dihydroartemisinin, the other was twice as potent. This exciting development will be reported in due course, Dr. Johnson says.

In spring 2024, a 26 foot U-Haul truck was used to transport 142 crates containing crude extracts, sponges, and repository documentation from UCSC to Dominican. Graduate students, postbaccs, and undergraduates in the Johnson Lab, along with two high school student volunteers, spent six months processing over 20,000 sponge-derived crude extract vials into crates. This same team also converted, cataloged, and transferred over 1,000 unextracted sponges into 1L glass jars from decomposing 2L Nalgene bottles that were originally used to transport the organisms from the IndoPacific back to the lab.

At Dominican, all science students can begin working in the lab their freshman year as part of the University's unique Research Methodology program. Through undergraduate research, students gain lifelong skills: how to structure an experiment, use laboratory equipment, record results, analyze data, and present their findings for peer review.

This hands-on curriculum, which continues in Dominican's Master's of Biological Sciences program, provides a unique experience for undergraduates, contributes to the success of faculty research programs, and prepares students for success in industry, graduate school, and medical school.

Projects that have emerged from the Johnson Lab have already served as a cornerstone to propel junior scientists to the next phase of their career by providing them research opportunities in the physical or natural sciences at the interface of chemistry and biology as they relate to health and medicine.

Sofia Odronwas was recently accepted to her first choice for medical school at the University of Washington. Natalie Oyler will study for her PhD in Cancer Immunology and Immunotherapy through the Moffitt Cancer Center at University of South Florida. Joe Gerke was accepted to his first choice for medical school at the Pacific Northwest University of Health Sciences (PNUHS). Jacob Peterson participated on two key scientific diving expeditions for the Johnson Lab while preparing his file for medical school. He worked with a team of divers in Bali to survey mariculture studies with sponges that are a source of a chemical probe used in biotechnology to study the cell cycle. These mariculture studies serve as a pilot program to pay locals to harvest sponges as an alternative to fish bombing. Jacob presented his findings at a seminar at Dominican. He was accepted to Pacific Northwest University of Health Sciences, Griffith University in Australia, and California' s Touro University for medical school.

"Dominican now has an incredible resource on site to harness for launching the next wave of scientists or physicians on their paths forward to accelerate biomedical research and to have fun doing it," Dr. Johnson says.

"Having precisely 1,290 unextracted IndoPacific marine sponges and 13,792 sponge-derived crude extracts to explore is vast," he adds. "Dominican's nascent sea sponge repository will be a beacon for motivated science students to investigate for their potential to advance discoveries in biomedical research for years to come."

_{Pictured. From left: Dr. Tyler Johnson, Natalie Oyler, Victoria Barlow, Brisa Navarette, Matt Nickel, and Brook Young.}

Tags:

• School of Health and Natural Sciences
• Natural Sciences and Mathematics
• Faculty Research
• Chemistry and Biochemistry
• Undergraduate Research