Category Archives: College of Science

The bacteria living inside us and what they have to say about autism

Trillions of bacterial cells are living within us and they’re controlling your brain activity.

Grace Deitzler is a 2nd year PhD student in microbiology working in Dr. Maude David’s lab on the gut-microbiome and its relation to autism spectrum disorder.

The gut-microbiome is the total population of bacteria living within our digestive tract. These bacteria are critical for digestive health, but also for our immune system and mental health. For example, we harbor bacteria capable of digesting plant fibres we otherwise could not digest. And if you’ve been told that probiotics are good for you, that’s because probiotics can change the gut microbiome in a positive way, allowing for increased bacterial diversity associate with improved health. These bacteria communicate with each other through chemical signaling but also communicate with us. Tryptophan, for example, is an amino acid produced through bacteria metabolism and is a precursor for serotonin, a brain-signaling chemical which causes feelings of happiness.

When the gut communicates with the brain, we call this, the “gut-brain axis”. Grace’s work narrows in on the gut-brain axis and more specifically, how one bacterial species in particular impacts autism spectrum disorder. To further complicate things, the gut-microbiome helps to regulate estrogen levels, and we also know that autism is a disorder found primarily in biological males. Which leads Grace to one of her biggest questions: are the bacteria involved in endocrine system regulation in women, also that responsible for this variation we see. Grace uses a mouse model to elucidate underlying mechanisms at play.

Step one is to feed the mice bacteria that have been found in elevated amounts in people with autism spectrum disorder than in neurotypical peers. These bacteria will colonize in the gut, and mice will go through several behavioral tests to determine if they are exhibiting more behaviors associated with autism. Grace performs three types of tests with the mice: one to test inclination to form repetitive behaviors, one to test anxiety, and one to test social behaviors. One test is a marble-burying test, in which a mouse more inclined to form repetitive behaviors will bury more marbles.

After behavioral testing is complete, the mice are sacrificed and different regions of the gut are taken to look for presence of bacterium. Tissues taken from the mice are used to look for transcriptional markers. The transcriptome is collected for both the mouse and the bacteria present, or the sum total of all genes that are read and converted to RNA. RNA are able to be isolated and sequenced using distinctive markers such as a “poly-A tail”. After this data is collected, Grace can finally move to the computational side of her work which involves combining biological and biochemical data with her behavioral studies.

In addition to her work on autism spectrum disorder, Grace also has a side project working in a honey bee lab, looking at the gut microbiome of honey bees in response to probiotics on the market for beekeepers. But Grace is one very busy bee herself because in addition to her lab work, she’s also involved with an art-science club called “seminarium”. The club is filled with scientists interested in art and artists interested in science. Grace is a painter primarily but is also working on ink illustration. The focus of this group is that art and science are complimentary, not at odds. The group has produced some collaborative projects, including a performance for a lab studying a parasite that effects salmon. The group put together a collage of interpretations of the parasites and had a performance in which one member played piano while someone else drew the parasite live.

Grace moved to Oregon from St. Louis Missouri. She completed her undergraduate degree in biological sciences with minors in chemistry and psychology at a small engineering college, Missouri University of Science and Technology, where she was a radio DJ! Grace first became involved in research during a summer internship in a microbiology lab at Washington University. There she studied the vaginal microbiome and how it effects pregnancy outcomes. Grace went back to this lab for the next couple summers and produced 4 publications! Ultimately, Grace graduated college early after they offered her a full time research position where she worked for a year and a half as a research tech. Through this experience, Grace came to realize that medical school was not her path, canceled her scheduled MCAT and signed up for GRE. Grace looked for schools in the PNW because she knew she wanted to live there, got an interview at OSU, loved it, and here we are!

Join us at 7 pm on Sunday, August 11th, 2019, to hear more about Grace’s research and her journey to OSU. Stream the show live on KBVR Corvallis 88.7FM or check out the episode as a podcast after a few weeks.

Micro structures and macro support

Our guest this week, Shauna Otto from the Department of Biochemistry and Biophysics, is a member of the lab of Dr. Colin Johnson. The focus of the Johnson lab is a group of proteins called ferlins. The ferlin family of proteins have many different functions, and many are involved in the fusion of vesicles to cell membranes in a process called, “exocytosis.” Another example is the protein otoferlin which fuses vesicles carrying neurotransmitters to the cell membrane of neurons in the inner ear that play a crucial role in hearing. See more about otoferlin from past guests from the Johnson lab, Murugesh Padmanarayana and Nicole Hams.

Shauna loading a sample for Cobalt-60 irradiation at the Notre Dame Radiation Laboratory.

Shauna studies dysferlin, another ferlin protein, which helps mend membrane tears in muscle cells. Mutations in the dysferlin gene lead to Muscular Dystrophy II. Through her work, Shauna has characterized portions or “domains” of the large dysferlin protein via Nuclear Magnetic Resonance (NMR). NMR is a process by which the magnetic field around the nuclei of atoms in a protein domain are excited, and by recording the magnitude of that disruption, Shauna can learn the structure of the domain. Her focus domain putatively binds other proteins that join dysferlin in a protein complex that initiates muscle cell membrane repair. However, the mechanism by which dysferlin bind repair proteins is unclear. Through her explorations with dysferlin, Shauna has found that an increase in Calcium leads to the stabilization of the dysferlin domains that might initiate repair. Right now, it is unclear if this stabilization initiates muscle cell repair, but if it does the next question is how and when such stabilization occurs.

Shauna and husband (Kris Hill) backpacking in Yosemite

Shauna’s academic journey was wrought with hardship, and we are grateful to her for being willing to share her story with us on air. Shauna started undergraduate with an interest in marine biology, but found that college is cost prohibitive. After a two year break, she went back to University of California Long Beach to major in Chemical Engineering, but finally landed on biochemistry. She had a knack for chemistry and loved solving complex puzzles in cellular biology through the lens of protein interactions and biochemical pathways. She began undergraduate research, but her work took a turn as she struggled with homelessness. Homelessness is a growing problem for college students, and has prompted bills targeting the problem of home insecurity for students in California and Washington. However, for Shauna, homelessness was not discussed among fellow students and officials when she attended school. Rather, instead of resources to alleviate her financial hardship, she was met with policy allowances such as permission to sleep in her research lab.

Shauna and her daughter in a bookshop.

Since beginning her PhD at OSU, Shauna has found support here on campus from mentors and her department who have listened and replied with support in the form of University Resources and Services to help her succeed academically, financially, and in personal wellness. Given her past, Shauna now knows the questions to ask about support when seeking the next job, and she is a resource for undergraduates and graduate students who are going through similar life experience.

Hear more about Shauna’s research and personal story this Sunday June 2, 2019 at 7 pm on KBVR Corvallis 88.7FM. Stream the show live or catch the episode as a podcast in the coming weeks.

Zebrafish sentinels: studying the effects of cadmium on biology and behavior

Cadmium exposure is on the rise

There’s a good chance you might have touched cadmium today. A heavy metal semi-conductor used in industrial manufacturing, cadmium is found in batteries and in some types of solar panels. Fertilizers and soil also contain cadmium because it is present in small levels in the Earth’s crust. The amount of cadmium in the environment is increasing because of improper disposal of cell phone batteries, contaminating groundwater and soil. This is a problem that impacts people all over the world, particularly in developing countries.

Plants take up cadmium from the soil, which is how exposure through food can occur. Leafy greens like spinach and lettuce can contain high levels of cadmium. From the soil, cadmium can leach into groundwater, contaminating the water supply. Cadmium is also found in a variety of other foods, including chocolate, grains and shellfish, as well as drinking water.

Cadmium has a long half-life, reaching decades, which means that any cadmium you are exposed to will persist in your body for a long time. Once in the body, cadmium ends up in the eyes or can displace minerals with similar chemical properties, such as zinc, copper, iron, and calcium. Displacement can cause grave effects related to the metabolism of those minerals. Cadmium accumulation in the eyes is linked to age-related macular degeneration, and for people in the military and children, elevated cadmium is linked to psychosocial and neurological disorders.

Read more about cadmium in the food supply:



Using zebrafish to study the effects of cadmium

Delia Shelton, a National Science Foundation post-doctoral fellow in the Department of Environmental and Molecular Toxicology, uses zebrafish to investigate how cadmium exposure in an individual affects the behavior of the group. Exposing a few individuals to cadmium changes how the group interacts and modifies their response to novel stimuli and environmental landmarks, such as plants. For example, poor vision in a leader might lead a group closer to predators, resulting in the group being more vulnerable to predation.

Zebrafish

As part of her post-doctoral research, Delia is asking questions about animal behavior in groups: how does a zebrafish become a leader, how do sick zebrafish influence group behavior, and what are the traits of individuals occupying different social roles? These specific questions are born from larger inquiries about what factors lead to individual animals wielding inordinately large influence on a group’s social dynamic. Can we engineer groups that are resilient to anthropogenic influences on the environment and climate change?

Zebrafish

Zebrafish are commonly used in biomedical research because they share greater than 75% similarity with the human genome. Because zebrafish are closely related to humans, we can learn about human biology by studying biological processes in zebrafish. Zebrafish act as a monitoring system for studying the effects of compounds and pollution on development. It is possible to manipulate their vision, olfactory system, level of gene expression, size, and aggression level to study the effects of pollutants, drugs, or diseases. As an added benefit, zebrafish are small and adapt easily to lab conditions. Interestingly, zebrafish are transparent, so they are great for imaging. Zebrafish have the phenomenal ability to regenerate their fins, heart and brain. What has Delia found? Zebrafish exposed to cadmium are bolder and tend to be attracted more to novel stimuli, and they have heightened aggression.

Read more about zebrafish:

ZFIN- Zebrafish Information Network – https://zfin.org/
Zebrafish International Research Center in Eugene Or – http://zebrafish.org/home/guide.php



What led Delia to study cadmium toxicity in zebrafish?

As a child, Delia was fascinated by animals and wanted to understand why they do the things they do. As an undergrad, she enjoyed research and pursued internships at Merck pharmaceutical, a zoo consortium, and Indiana University where she worked with Siamese fighting fish. She became intrigued by social behavior, social roles, and leadership. Delia studied the effects of cadmium in grad school at Indiana University, and decided to delve into this area of research further.

Delia began her post-doctoral work after she finished her PhD in 2016. She was awarded an NSF Postdoctoral Fellowship to complete a tri-institute collaboration: Oregon State University, Leibniz Institute for Freshwater Ecology and Inland Fisheries in Berlin, Germany, and University of Windsor in Windsor, Ontario. She selected the advisors she wanted to work with by visiting labs and interviewing past students. She wanted to find advisors she would work well with and who would help her to accomplish her goals. Delia also outlined specific goals heading into her post-doc about what she wanted to accomplish: publish papers, identify collaborators, expand her funding portfolio, learn about research institutes, and figure out if she wanted to stay in academia.

Research commercialization and future endeavors

During her time at OSU, Delia developed a novel assay to screen multiple aspects of vision, and saw an opportunity to explore commercialization of the assay. She was awarded a grant through the NSF Innovation Corps and has worked closely with OSU Accelerator to pursue commercialization of her assay. Delia is now wrapping up her post-doc, and in the fall, she will begin a tenure track faculty position at University of Tennessee in the Department of Psychology, where she will be directing her lab, Environmental Psychology Innovation Center (E.P.I.C) and teaching! She is actively recruiting graduate students, postdocs, and other ethnusiatic individuals to join her at EPIC.

Please join us tonight as we speak with Delia about her research and navigation of the transition from PhD student to post-doc and onwards to faculty. We will be talking to her about her experience applying for the NSF Postdoctoral Fellowship, how she selected the labs she wanted to join as a post-doc, and her experience working and traveling in India to collect zebrafish samples.

Tune in to KBVR Corvallis 88.7 FM or stream the show live on Sunday, April 7th at 7 PM. You can also listen to the episode on our podcast.

Magnet blocks, connect the dots, and the world of modern mathematics

At the Mathematical Sciences Research Institute in Berkely, CA with the Klein quartic sculpture. Photo by Charles Camacho

Charles Camacho, a sixth-year PhD student in the Department of Mathematics at Oregon State University, spends a lot of time thinking about shapes. He describes his research as such: “I study the symmetries of abstract mathematical surfaces made from gluing triangles together.”

Charles explaining his thesis research at the Latinx in the Mathematical Sciences conference at UCLA. Photo by Farida Saleh from the Daily Bruin.

Charles works in a branch of mathematics called topology. Topologists think about shapes and surfaces. There’s a joke among mathematicians that a topologist is someone who can’t tell the difference between a coffee cup and a donut, and there’s some truth to that. It’s not that they can’t see a difference, but that they look past the difference to see the core similarity: both are solid objects punctured with a single hole. Topology as a formal area of mathematics is fairly recent (early 20th century). Topology’s roots go much further back, though, through the streets of Königsberg in the 1700s and to the geometry of the ancient Greeks.

Königsberg bridge problem
There’s a famous puzzle that originated in  Königsberg, Prussia in the 1700s (Königsberg is now Kaliningrad, Russia). The puzzle didn’t originate among mathematicians—but my understanding is that it’s mainly mathematicians that think about the puzzle now. Back then, there were seven bridges crossing the river Preger.

The Bridges of Königsberg (illustration by Leonard Euler, 1736).

The puzzle is this: Is it possible to cross each one of the seven bridges exactly once? (Go on, try it!) In his description of the problem and its solution, Euler said “it neither required the determination of quantities, nor did calculation with quantities help towards its solution.” He was interested in solving this superficially trivial problem because he couldn’t see a way for algebra, counting, or geometry to solve it. This goes against most people’s conception of mathematics—can it really be a math problem if you don’t fill a chalkboard with calculations?

The fact that no one yet had found a way to cross all the bridges without a repeat did not prove that it could not be done. To do that, and thus solve the problem for good, Euler had the insight to try and reduce the problem to its core. Reframing the Königsberg Bridges problem (elements of image from Wikimedia Commons, composited graphic by Daniel Watkins)
Knowing the layout of the city and all of its streets is irrelevant, so we can simplify to a map of just bridges. But even knowing that there is a river and land doesn’t really matter. All we really need is to know is represented in the network on the right (what mathematicians today call a graph). Euler’s solution was this: “If there are more than two regions with an odd number of bridges leading into them, then it can safely be stated that there is no such crossing.” It didn’t matter where the bridges were, it just mattered how many of the possible paths led to each landmass.

With collaborators at a summer research workshop on graph theory. Photo copyright American Mathematical Society

Being a mathematician, Euler wasn’t satisfied just stating a solution to the Königsberg problem. He went further, and generalized: he came up with rules and a solution that would work for any city with any number of bridges. All you have to do is look at the crossings, and note whether there’s an odd number of ways to get there, or an even number of ways. Euler’s method was developed by later mathematicians into graph theory, a branch of mathematics focusing on sets of points and the paths connecting them. Graph theory has a reputation for having many problems that are simple to state, but incredibly difficult to solve conclusively. In this sense, graph theory has a lot in common with geometric toy blocks.

Platonic solids
Charles has a set of magnetic toys in familiar shapes: triangles, squares, pentagons. These shapes are known as regular polygons, which just means that they are shapes composed of straight lines, each of which has the same length. Playing with these, one can hardly help but to arrange them into three-dimensional shapes. Playing with the triangles, you can quickly form a triangular pyramid: a tetrahedron. With six squares, a cube. With eight triangles, an octahedron. And with twelve pentagons, a dodecahedron. Surprisingly, there are only five shapes that can be made this way! Why is this the case? And must this always be the case?

The Platonic Solids: Tetrahedron, Cube, Octahedron, Dodecahedron, Icosahedron. Image copyright Daniel Watkins.

You might notice some other interesting things about these shapes. If you turn a cube while holding the middle of a side, you will see that it looks the same after each turn. It has rotational symmetry. Each of these shapes has multiple axis of symmetry. They can be rotated holding them in different ways and still show symmetry.

As a mathematician, Charles thinks about ways to generalize these ideas. We know that the five Platonic shapes are the only solids that can be formed from regular polygons, but what shapes could be formed if you used slightly different definitions? What if, for example, you used arcs of a circle to form the lines? What can we say about different kinds of surfaces? These shapes are defined on flat planes, like a piece of paper, but we know of lots of other surfaces, like the world we live on, that aren’t perfectly flat.  What kind of symmetry do polygons in these geometries show? Specifically, I wanted to know all the ways that such surfaces can be rotated a given number of times. I generalized previous research on counting symmetries and discovered a formula describing the number of these rotational symmetries,” Charles said.

A topological representation of a four-holed surface with a twelve-fold rotational symmetry (blue arrows indicate which edges are to be glued to make the surface. Graphic copyright Charles Camacho

Tune in to KBVR Corvallis 88.7 FM on Sunday March, 10 at 7 PM to hear more about Charles’s research, his inspirations, and his path to research in mathematics. Stream the show live or catch this episode as a podcast.

Treating the Cancer Treatment: an Investigation into a Chemotherapy drug’s Toxic Product

One of the most difficult hurdles in cancer treatment development is designing a drug that can distinguish between a person’s healthy cells and cancer cells. Cancerous cells take advantage of the body’s already present machinery and biochemical processes, so when we target these processes to kill cancer cells, normal, healthy cells are also destroyed directly or through downstream effects of the drug. The trick to cancer treatment then is to design a drug that kills cancer cells faster than it harms healthy cells. To this end, efforts are being made to understand the finer details that differentiate the anti-cancer effects of a drug from its harmful effects on the individual. This is where the research of Dan Breysse comes in.

Dan a third-year master’s student working with Dr. Gary Merrill in the department of Biochemistry and Biophysics. Dan’s research focuses on a common chemotherapy drug, doxorubicin. Doxorubicin has been researched and prescribed for about 40 years and has been used as a template over the years for many other new drug derivatives. This ubiquitous drug can treat many types of cancer but the amount that can be administered is limited by its toxic effect on the individual. Nicknamed “the red death,” doxorubicin is digested and ultimately converted to doxorubicinol, which in high doses can cause severe and fatal heart problems. However, hope lies in the knowledge that doxorubicinol generation is not related to the drug’s ability to kill cancer cells. These mechanisms appear to be separate, meaning that there is potential to prevent the heart problems, while keeping the anti-cancer process active.

Cancer cells replicate and build more cellular machinery at a much faster rate than the majority of healthy cells. Doxorubicin is more toxic to fast-replicating cancer cells because its mechanism involves attacking the cells at the DNA level. Dividing cells need to copy DNA, so this aspect of doxorubicin harms dividing cells faster than non-dividing cells. It is common for chemotherapy drugs to target processes more detrimental to rapidly dividing cells which is why hair loss is often associated with cancer treatment.

Separately, doxorubicin’s heart toxicity appears to be regulated at the protein level rather than at the DNA level. Doxorubicin is converted into doxorubicinol by an unknown enzyme or group of enzymes. Enzymes are specialized proteins in the cell that help speed up reactions, and if this enzyme is blocked, the reaction won’t occur. For example, an enzyme called “lactase” is used to break down the sugar lactose, found in milk. Lactose intolerance originates from a deficiency in the lactase enzyme. During his time at OSU, Dan has been working to find the enzyme or enzymes turning doxorubicin into doxorubicinol and to understand this chemical reaction more clearly. Past research has identified several potential enzymes, one of which being Carbonyl reductase 1 (CBR1).

Doxorubicin is converted to doxorubicinol with the addition of a single hydrogen atom.

While at OSU, Dan has ruled out other potential enzymes but has shown that when CBR1 is removed, generation of doxorubicinol is decreased but not completely eliminated, suggesting that it is one of several enzymes involved. In the lab, Dan extracts CBR1 from mouse livers, and measures its ability to produce doxorubicinol by measuring the amount of energy source consumed to carry out the process. To extract and study CBR1, Dan uses a process called “immunoclearing,” which takes advantage of the mammal’s natural immune system. Rabbits are essentially vaccinated with the enzyme of interest, in this case, with CBR1. The rabbit’s immune system recognizes that something foreign has been injected and the system creates CBR1-specific antibodies which can recognize and bind to CBR1. These antibodies are collected from the rabbits and are then used by Dan and other researchers to bind to and purify CBR1 from several fragments of mouse livers.

Prior to his time at OSU, Dan obtained a B.S. in Physics with a concentration in Biophysics from James Madison University where he also played the French horn. Realizing he loved to learn about the biological sector of science but not wanting to completely abandon physics, Dan applied to master’s programs specific to biophysics. Ultimately, Dan hopes to go to medical school. During his time at OSU, he has balanced studying for the MCAT, teaching responsibilities, course loads, research, applying to medical schools, and still finds time to play music and occasionally sing a karaoke song or two.

To hear more about Dan’s research, tune in Sunday, December 16th at 7 PM on KBVR 88.7 FM, live stream the show at http://www.orangemedianetwork.com/kbvr_fm/, or download our podcast on iTunes!

Infection Interruption: Identifying Compounds that Disrupt HIV

Know the enemy

Comparing microbial extracts with Dr. Sandra Loesgen.

The Human Immunodeficiency Virus, or HIV, is the virus that leads to Acquired Immunodeficiency Syndrome (AIDS). Most of our listeners have likely heard about HIV/AIDS because it has been reported in the news since the 1980s, but our listeners might not be familiar with the virus’s biology and treatments that target the virus.

  • HIV follows an infection cycle with these main stages:
    • Attachment – the virus binds to a host cell
    • Fusion – the viral wall fuses with the membrane of the host cell and genetic material from the virus enters the host cell
    • Reverse transcription – RNA from the virus is converted into DNA via viral enzymes
    • Integration – viral DNA joins the genome of the host cell
    • Reproduction – the viral DNA hijacks the host cell activity to produce more viruses and the cycle continues
  • Drug treatments target different stages in the HIV infection cycle to slow down infection
  • However, HIV has adapted to allow mistakes to occur during the reverse transcription stage such that spontaneous mutations change the virus within the host individual, and the virus becomes tolerant to drug treatments over time.

Faulty Machinery

Due to the highly mutable nature of HIV, a constant supply of new drug treatments are necessary to fend off resistance and treat infection. Our guest this week on Inspiration Dissemination, Ross Overacker a PhD candidate in Organic Chemistry, is screening a library of natural and synthetic compounds for their antiviral activity and effectiveness at disrupting HIV. Ross works in a Natural Products Lab under the direction of Dr. Sandra Loesgen. There, Ross and his lab mates (some of whom were on the show recently [1] [2]) test libraries of compounds they have extracted from fungi and bacteria for a range of therapeutic applications. Ross is currently completing his analysis of a synthetic compound that shows promise for interrupting the HIV infection cycle.

“Uncle Ross” giving a tour of the lab stopping to show off the liquid nitrogen.

Working in Lab with liquid nitrogen.

 

 

 

 

 

 

 

Havin’ a blast

Chemistry Club at Washington State University (WSU) initially turned Ross onto chemistry. The club participated in education outreach by presenting chemistry demonstrations at local high schools and club events. Ross and other students would demonstrate exciting chemistry demos such as filling hydrogen balloons with salt compounds resulting in colorful explosions piquing the interest of students and community members alike. Ross originally made a name in

Collecting Winter Chanterelles in the Pacific Northwest.

WSU’s chemistry club, eventually becoming the president, by showing off a “flaming snowball” and tossing it from hand to hand—don’t worry he will explain this on air. For Ross, chemistry is a complicated puzzle that once you work out, all of the pieces fall into place. After a few undergraduate research projects, Ross decided that he wanted to continue research by pursing a PhD in Organic Chemistry at Oregon State University.

 

 

Tune in this Sunday October 7th at 7 PM to hear from Ross about his research and path to graduate school. Not a local listener? Stream the show live or catch this episode on our podcast.

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.

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.

Aquatic Invertebrates: Why You Should Give a Dam

Rivers are ecosystems that attract and maintain a diversity of organisms. Fish, birds, mammals, plants, and invertebrates live in and around rivers. Have you considered what services these groups of organisms provide to the river ecosystem? For example, river invertebrates provide numerous ecosystem services:

Dragonfly larvae caught in in the waters of a small stream flowing into the Grand Canyon.

  • Insects and mussels improve water quality by fixing nutrients, such as those from agricultural runoff.
  • River invertebrates are food resources for fish, bats, birds, and other terrestrial organisms.
  • Grazing insects can control and/or stimulate algal growth.
  • Mussels can help to stabilize the bed of the river.

High school students are the best helpers for sampling aquatic insects!

And the list continues. These invertebrates have adapted to the native conditions of their river ecosystem, and major disturbances, such as a change in the flow of a river from a dam, can change the community of organisms downstream. If dams decrease the diversity of invertebrates downstream, then they may also decrease the diversity of ecosystem services offered by the invertebrate community.

Our guest this week, Erin Abernethy PhD candidate from the department of Integrative Biology, is investigating the community structure (or the number of species and the number of individuals of each species) of freshwater aquatic invertebrates downstream of dams. Specifically, Erin wants to know if invertebrate communities near dams of the Colorado River are different than those downstream, and which factors of dams of the Southwest US affect invertebrate communities.

Getting to field sites in the Grand Canyon is easiest by raft! It’s a pretty float, too!

Erin’s dissertation also has a component of population genetics, which examines the connectivity of populations of mayflies,populations of caddisflies, and populations of water striders. The outcomes of Erin’s research could inform policy around dam operation and the maintenance of aquatic invertebrate communities near dams.

“One must dress for sampling success in the Grand Canyon!” said this week’s guest, Erin Abernethy, who is pictured here.

Growing up, Erin participated in many outdoor activities with her parents, who are biologists. She became interested in how dams effect ecology, specifically fresh water mussels, doing undergraduate research at Appalachian State University. After undergrad, Erin completed a Master’s in Ecology from University of Georgia. She was investigating the foraging behavior of animals in Hawaii. This involved depositing animal carcasses and monitoring foraging visitors. Check out Erin’s blog for photos of these animals foraging at night! Erin decided to keep going in academia after being awarded a Graduate Research Fellowship, which landed her a position in David Lytle’s lab here at Oregon State. After she completes her PhD, Erin is interested in working for an agency or a nonprofit as an expert in freshwater ecology and the maintenance of biodiversity in freshwater ecosystems.

 

Tune in at 7 pm this Sunday February, 25 to hear more about Erin’s research and journey to graduate school. Not a local listener? Stream the show live.

Exploring a protein’s turf with TIRF

Investigating Otoferlin

Otoferlin is a protein required for hearing. Mutations in its gene sequence have been linked to hereditary deafness, affecting 360 million people globally, including 32 million children. Recently graduated PhD candidate Nicole Hams has spent the last few years working to characterize the activity of Otoferlin using TIRF microscopy. There are approximately 20,000 protein-coding genes in humans, and many of these proteins are integral to processes occurring in cells at all times. Proteins are encoded by genes, which are comprised of DNA; when mutations in the gene sequence occur, diseases can arise. Mutations in DNA that give rise to disease are the focus of critical biomedical research. “If DNA is the frame of the car, proteins are the engine,” explains Nicole. Studying proteins can provide insight into how diseases begin and progress, with the strategic design of therapies to treat disease founded on our understanding of protein structure and function.

Studying proteins

Proteins are difficult to study because they’re so small: at an average size of ~2 nanometers (0.000000002 meters!), specific tools are required for visualization. Enter TIRF. Total Internal Reflection Fluorescence is a form of microscopy enabling scientists like Nicole to observe proteins tagged with a fluorescent marker. One reason TIRF is so useful is that it permits visualization of samples at the single molecule level. Fluorescently-tagged proteins light up as bright dots against a dark background, indicating that you have your protein.

Another reason why proteins are hard to study is that in many cases, parts of the protein are not soluble in water (especially if part of the protein is embedded in the fatty cell membrane). Trying to purify protein out of a membrane is extremely challenging. Often, it’s more feasible for scientists to study smaller, soluble fragments of the larger protein. Targeted studies using truncated, soluble portions of protein offer valuable information about protein function, but they don’t tell the whole story. “Working with a portion of the protein gives great insight into binding or interaction partners, but some information about the function of the whole protein is lost when you study fragments.” By studying the whole protein, Nicole explains, “we can offer insight into mechanisms that lead to deafness as a result of mutations.”

Challenges and rewards of research

Nicole cites being the first person in her lab to pursue single molecule studies as a meaningful achievement in her graduate career. She became immersed in tinkering with the new TIRF instrument, learning from the ground up how to develop new experiments. Working with cells containing Otoferlin, in a process known as tissue culture, required Nicole to be in lab at unusual hours, often for long periods of time, to make sure that the cells wouldn’t die. “The cells do not wait on you,” she explains, adding, “even if they’re ready at 3am.” Sometimes Nicole worked nights in order to get time on the TIRF. “If you love it, it’s not a sacrifice.”

Why grad school?

As an undergraduate student studying Agricultural Biochemistry at the University of Missouri, Nicole worked in a soybean lab investigating nitrogen fixation, and knew she wanted to pursue research further. She had worked in a lab work since high school, but didn’t realize it was a path she could pursue, instead convinced that she wanted to go to medical school. Nicole’s mom encouraged her to pursue research, because she knew that it was something she enjoyed, and her undergraduate advisor (who completed his post-doc at OSU) suggested that she apply to OSU. She feels lucky to have found an advisor like Colin Johnson, and stresses the importance of finding a mentor who is personally vested in their graduate student’s success.

Besides lab work…

In addition to research, Nicole has been actively involved in outreach to the community, serving as Educational Chair of the local NAACP Chapter. Following completion of her PhD, Nicole intends to continue giving back to the community, by establishing a scholarship program for underrepresented students. Nicole remembers a time when she was told and believed that she wasn’t good enough, and while she was able to overcome this discouraging dialogue, she has observed that many students do not find the necessary support to pursue higher education. Her goal is to reach students who don’t realize they have potential, and provide them with resources for success.

Tune in on December 3rd  at 7pm to 88.7 KBVR Corvallis or stream the show live right here to hear more about Nicole’s journey through graduate school!

Thanks for reading!

You can download Nicole’s iTunes Podcast Episode!

Earlier in the show we discussed current events, specifically how the tax bill moving through the House and Senate impact students. Please see our references and sources for more information.