Category Archives: Chemistry

The Mold That Keeps On Giving

All around us, plants, fungi, and bacteria are waging chemical warfare against one another to deter grazing, prevent against infection, or reduce the viability of competitor species. Us humans benefit from this. We use many of these compounds, called secondary metabolites, as antibiotics, medicines, painkillers, toxins, pigments, food additives, and more. We are nowhere close to finding all of these potentially useful compounds, particularly in marine environments where organisms can make very different types of chemicals. Could something as ordinary as a fungus from the sea provide us with the next big cancer breakthrough?

Paige Mandelare with one of the many marine bacteria she works with

Paige Mandelare thinks so. As a fourth-year PhD student working for Dr. Sandra Loesgen in OSU’s Chemistry department, she has extracted and characterized a class of secondary metabolites from a marine fungus, Aspergillus alliaceus, isolated from the tissues of an algae in the Mediterranean Sea. After growing the fungus in the laboratory and preparing an extract from it, she tested the extract on colon cancer and melanoma cell lines. It turned out to be cytotoxic to these cancer cells. Further purification of this mixture revealed three very similar forms of these new compounds they called allianthrones. Once Paige and her research group narrowed down their structures, they published their findings in the Journal of Natural Products.

Next, she grew the fungus on a different salt media, replacing bromine for chlorine. This forced the fungus to produce brominated allianthrones, which have a slightly different activity than the original chlorinated ones. Her lab then sent two of these compounds to the National Cancer Institute, where they were tested on 60 cell lines and found to work most effectively on breast cancers.

The recent publication of Paige in her story of the allianthrones from this marine-derived fungus, Aspergillus alliaceus.Like many organisms that produce them, this wonder mold only makes secondary metabolites when it has to. By stressing it with several different types of media in the lab, Paige is using a technique called metabolomics to see what other useful compounds it could produce. This will also give insight into how the fungus can be engineered to produce particular compounds of interest.

A native Rhode Islander who moved to Florida at the age of ten, Paige has always been fascinated with the ocean and as a child dreamed of becoming a marine biologist and working with marine mammals. She studied biology with a pre-med track as an undergraduate at the University of North Florida before becoming fascinated with chemistry. Not only did this allow her to better appreciate her father’s chemistry PhD better, she joined a natural products research lab where she first learned to conduct fungal chemical assays. Instead of placing her on a pre-med career path, her mentors in the UNF Chemistry department fostered her interest in natural products and quickly put her in touch with Dr. Loesgen here at OSU.

Paige enjoying her time at the Oregon Coast, when she is not in the research lab

After finishing her PhD, Paige hopes to move back east to pursue a career in industry at a pharmaceutical company or startup. In the meantime, when she’s not discovering anticancer agents from marine fungi, she participates in a master swimming class for OSU faculty, trains for triathlons, and is an avid baker.

To hear more about Paige and her research, tune in to KBVR Corvallis 88.7 FM this Sunday July 15th at 7 pm. You can also stream the live interview at kbvr.com/listen, or find it on our podcast next week on Apple Podcasts.

Ocean sediment cores provide a glimpse into deep time

Theresa on a recent cruise on the Oceanus.
Photo credit: Natasha Christman.

First year CEOAS PhD student Theresa Fritz-Endres investigates how the productivity of the ocean in the equatorial Pacific has changed in the last 20,000 years since the time of the last glacial maximum. This was the last time large ice sheets blanketed much of North America, northern Europe, and Asia. She investigates this change by examining the elemental composition of foraminifera (or ‘forams’ for short) shells obtained from sediment cores extracted from the ocean floor. Forams are single-celled protists with shells, and they serve as a proxy for ocean productivity, or organic matter, because they incorporate the elements that are present in the ocean water into their shells. Foram shell composition provides information about what the composition of the ocean was like at the point in time when the foram was alive. This is an important area of study for learning about the climate of the past, but also for understanding how the changing climate of today might transform ocean productivity. Because live forams can be found in ocean water today, it is possible to assess how the chemistry of seawater is currently being incorporated into their shells. This provides a useful comparison for how ocean chemistry has changed over time. Theresa is trying to answer the question, “was ocean productivity different than it is now?”

Examples of forams. For more pictures and information, visit the blog of Theresa’s PI, Dr. Jennifer Fehrenbacher: http://jenniferfehrenbacher.weebly.com/blog

Why study foram shells?

Foram shells are particularly useful for scientists because they preserve well and are found ubiquitously in ocean sediment, offering a consistent glimpse into the dynamic state of ocean chemistry. While living, forams float in or near the surface of the sea, and after they die, they sink to the bottom of the sea floor. The accumulating foram shells serve as an archive of how ocean conditions have changed, like how tree rings reflect the environmental conditions of the past.

Obtaining and analyzing sediment cores

Obtaining these records requires drilling cores (up to 1000 m!) into deep sea sediments, work that is carried out by an international consortium of scientists aboard large ocean research vessels. These cores span a time frame of 800 million years, which is the oldest continuous record of ocean chemistry. Each slice of the core represents a snapshot of time, with each centimeter spanning 1,000 years of sediment accumulation. Theresa is using cores that reach a depth of a few meters below the surface of the ocean floor. These cores were drilled in the 1980s by a now-retired OSU ship and are housed at OSU.

Theresa on a recent cruise on the Oceanus, deploying a net to collect live forams. Photo credit: Natasha Christman.

The process of core analysis involves sampling a slice of the core, then washing the sediment (kind of like a pour over coffee) and looking at the remainder of larger-sized sediment under a powerful microscope to select foram species. The selected shells undergo elemental analysis using mass spectrometry. Vastly diverse shell shapes and patterns result in different elements and chemistries being incorporated into the shells. Coupled to the mass spectrometer is a laser that ablates through the foram shell, providing a more detailed view of the layers within the shell. This provides a snapshot of ocean conditions for the 4 weeks-or-so that the foram was alive. It also indicates how the foram responded to light changes from day to night.

Theresa is early in her PhD program, and in the next few years plans to do field work on the Oregon coast and on Catalina island off the coast of California. She also plans to undertake culturing experiments to further study the composition of the tiny foram specimens.

Why grad school at OSU?

Theresa completed her undergraduate degree at Queen’s University in Ontario, followed by completion of a Master’s degree at San Francisco State University. She was interested in pursuing paleo and climate studies after transformative classes in her undergrad. In between her undergraduate and Master’s studies she spent a year working at Mt. Evans in Colorado as part of the National Park Service and Student Conservation Association.

Theresa had already met her advisor, Dr. Jennifer Fehrenbacher, while completing her Master’s degree at SF State. Theresa knew she was interested in attending OSU for grad school for several reasons: to work with her advisor, and to have access to the core repository, research ships, and technical equipment available at OSU.

To hear more about Theresa’s research and her experience as a PhD student at OSU, tune in on Sunday, June 10th at 7pm on KBVR Corvallis 88.7 FM, or listen live at kbvr.com/listen.  Also, check us out on Apple Podcasts!

When Fungus is Puzzling: A Glimpse into Natural Products Research

Ninety years ago, a fungal natural product was discovered that rocked the world of medicine: penicillin. Penicillin is still used today, but in the past ninety years, drug and chemical resistance have become a hot topic of concern not only in medicine, but also in agriculture. We are in desperate need of new chemical motifs for use in a wide range of biological applications. One way to find these new compounds is through natural products chemistry. Over 50% of drugs approved in the last ~30 years have been impacted by natural products research, being directly sourced from natural products or inspired by them.

Picture a flask full of microbe juice containing a complex mixture of hundreds or thousands of chemical compounds. Most of these chemicals are not useful to humans – in fact, useful compounds are exceedingly rare. Discovering new natural products, identifying their function, and isolating them from a complex mixture of other chemicals is like solving a puzzle. Donovon Adpressa, a 5th year PhD candidate in Chemistry working in the Sandra Loesgen lab, fortunately loves to solve puzzles.

Nuclear Magnetic Resonance (NMR): an instrument used to elucidate the structure of compounds.

Donovon’s thesis research involves isolating novel compounds from fungi. Novel compounds are identified using a combination of separation and analytical chemistry techniques. Experimentally, fungi can be manipulated into producing compounds they wouldn’t normally produce by altering what they’re fed. Fungi exposed to different treatments are split into groups and compared, to assess what kind of differences are occurring. By knocking out certain genes and analyzing their expression, it’s possible to determine how the compound was made. Once a new structure has been identified and isolated, Donovon moves on to another puzzle: does the structure have bioactivity, and in what setting would it be useful?

Donovon’s interest in chemistry sparked in community college. While planning to study Anthropology, he took a required chemistry course. Not only did he ace it, but he loved the material. The class featured a one-week lecture on organic chemistry and he thought, ‘I’m going to be an organic chemist.’ However, there were no research opportunities at the community college level, and he knew he would need research experience to continue in chemistry.

At Eastern Washington University, Donovon delved into undergraduate research, and got to work on a few different projects combining elements of medicinal and materials chemistry. While still an undergrad, Donovon had the opportunity to present his research at OSU, which provided an opportunity to meet faculty and see Corvallis. It all felt right and fell into place here at OSU.

As a lover of nature and hiking in the pacific northwest, Donovon has always had a soft spot for mycology. It was serendipitous that he ended up in a natural products lab doing exactly what interested him. Donovon’s next step is to work in the pharmaceutical industry, where he will get to solve puzzles for a living!

Tune in at 7pm on Sunday, March 18th to hear more about Donovon’s research and journey through graduate school. Not a local listener? Stream the show live.