When Samantha Yanders stepped to the front of Monsanto Auditorium, she followed presentations from two researchers with three degrees each.
Yanders only had three years of undergraduate research experience.
Nevertheless, she pinned the microphone to her tie, ran her fingers through her short curly hair, and explained her research with a calm certainty to her voice.
Having just finished her junior year as a plant science undergraduate, Yanders spent the first week of her summer sharing her passion for plants with fellow researchers during the 2022 Interdisciplinary Plant Group Symposium.
“I want to be inclusive in how I talk about my work to be able to educate people,” Yanders said. “Even if you’re talking to molecular biologists, they may have no idea about extracellular ATP.”
A clear communicator and advanced undergraduate researcher, Yanders was selected to present her research in Monsanto Auditorium during the symposium and often helps write and edit manuscripts for her lab.
Yanders began research in the Gary Stacey lab through Freshman Research in Plant Science, a program that places plant science freshmen in MU labs. Yanders’ research focuses on the signaling role of extracellular ATP when a plant experiences high-salt conditions.
Within a cell, ATP is a molecule used for energy. However, research shows that when a plant is in high stress or damaging conditions, ATP outside the cell signals for protective mechanisms.
“It’s really clever because instead of spending energy to make both a signaling molecule and a signal receptor, it already has something that’s really high concentrations in the cell and very low concentrations outside the cell,” Yanders said. “So it’s easy for the plant. It just has to make a signal receptor.”
Under normal conditions there is less ATP outside the cell and a high concentration of ATP inside the cell since it is used as energy. However, under high salt conditions there is an increase in ATP outside the cell, which binds to receptors on the cell surface that communicate with the cell to stunt plant growth. Yanders’ work explores the impact of high salt environments for plants — an increasingly relevant project as climate change raises sea levels and increases salt deposits in soil.
Although she now enthusiastically recounts her work to auditoriums of fellow scientists, biology was not originally Yanders’ first choice.
“In high school, I knew that I wanted to do something scientific because I’ve always liked science,” Yanders said, “But I didn’t think I wanted to go into biology, because I saw biology as mainly oriented towards animals.”
Sam Yanders shows the roots of arabidopsis plants. Yanders studies extracellular ATP in arabidopsis and tobacco plants. Photo by Cara Penquite | Bond LSC
With her geneticist grandfather piquing her interest from a young age and her enthusiasm for environmental science in high school, once she learned Mizzou had a plant science program she was ready to commit.
“So I was like, ‘Okay, I’ll go into biology and focus on plants.’ And then I’m looking on the Mizzou website and they [have] plant science. I didn’t even know that was a thing,” Yanders said. “So I switched to plant science.”
After enjoying high school chemistry labs, Yanders was ready to take the next step into research labs as soon as possible. Freshman Research in Plant Science allowed Yanders the opportunity to join a lab right away — fostering her interest in plant research.
“As humans, we move around. We can adapt to change by moving and changing what we do,” Yanders said. “But a plant has to do all of that management from a stationary position. . . It can’t change the circumstances that it’s in, so it has to adjust itself to be able to adapt.”
Tobacco plants grow under artificial light at Bond LSC. Photo by Cara Penquite | Bond LSC
Yanders’ love of plants extends beyond the walls of the lab, and she spends her free time in her herb garden where she learns more about plant and human interactions.
“The way that you interact with the plant fundamentally changes how the plant acts,” Yanders said. “So like with basil, if you just let a basil plant grow it just gets leggy and crazy, but if you do what you feel like is harming it by pinching the tops off, then it grows more compact and bushy, which is good for the plant.”
Yanders hopes to explore plant and human interactions in the future, potentially pursuing urban agriculture and ecology.
“I’m really interested in soil health, I feel like we’ve done a lot to deplete soils, and coming up with more renewable ways of doing things [and] producing things for human consumption,” Yanders said.
While uncertain which questions she will ask next, Yanders hopes to continue answering questions and explaining her research to others.
“[I like] being able to offer an explanation, and not just see it, but to create that explanation for other people,” Yanders said.
If the world can be taxing on a person as pressure mounts, just think about how stress must feel to plants.
Humans can add a layer of clothing when cold or get a glass of water when thirsty, but plants do not share this simple luxury and must endure whatever environment they sprout in.
As climate change, pollutants, and extreme weather patterns escalate, this poses a serious global threat to plants and our food supply.
Ron Mittler, a principal researcher at the Bond Life Sciences at the University of Missouri, recently looked at how this piling up of multiple stressors at once can significantly decrease plant survival.
“The principle is that you can have a combination of several different stressors, each by itself has no effect on the plant but when they come together, they’re causing severe effects,” Mittler said.
Studying plant response to stress isn’t a new thing, but Mittler’s focus on the compounded effects of stressors may give us a better idea of the threshold of stress plants can endure in our changing climate. Multifactorial stressors combine three or more stress factors simultaneously impacting plants. Four categories of stress— biotic, climate, anthropogenic, and soil threats — all become worse as climate change and environmental pollution progress, subsequently decreasing plant quality of life.
Biotic threats relate to enemies like pathogenic bacteria and insects. Similarly, soil threats are determined by poor nutrient soil and salinity. Climate threats include extreme temperatures and drought. Anthropogenic threats are man-made as humans use harmful pesticides and create microplastics.
Arabidopsis thaliana seedlings, a model plant used in experiments, were placed side by side on a plate and received a combination of stress conditions such as heat, salt, excess light, acidity, heavy metal, and oxidative stress. Researchers studied the growth, survival, and molecular responses of the seeds. Seedlings were grown on plates rather than in soil to isolate and study the impact of multifactorial stress.
Seedlings grew on separate plates and experienced different individual or combined stresses. Results showed that each individual stressor applied to the seedling had a minimal effect on the plants but with the increase in the complexity and number of stress factors affecting the plants, survival, root growth, and chlorophyll content declined. Similar results were also found for seedlings grown in soil.
Ecosystems are already seeing these impacts in Florida and Germany. Multifactorial stress of heat and pollution prompted algae blooms to grow exponentially. This toxic overgrowth led to thousands of manatees dying. Entire forests in Germany are experiencing massive storms followed by long periods of drought, insect attacks, and fires.
Mittler said things may not look dire now, but we will eventually reach a point of no return where plants die off in mass quantities or even go extinct.
“The harmful effects of stress on the nation can serve as a dire warning for society. We may not see the effects now but 10, 20, 40 years down the road we will be having severe problems with our food chain,” Mittler said.
Since there are multiple factors at stake, predicting negative impacts on agriculture and ecosystems is tricky as researchers are unsure how this domino effect may unravel. What they do know for certain is that there will be severe consequences and we are already seeing them today.
These sporadic weather extremes are weakening the plants, making them more vulnerable to insect predators and other stressors.
The research yielded alarming results, and Mittler highlights that this is a dire problem that people need to take seriously. Once people understand the severity of this problem, he hopes individuals and policymakers will take action before the consequences become irreversible.
The Mittler lab is working on several fronts to address this problem and is trying to find a solution to it. They are currently studying multifactorial stress combination in different crop species, such as soybean, rice, and tomato. In addition, also identifying key plant regulators that are activated during multifactorial stress combination. These will be used in future breeding efforts to increase the tolerance of different crops to multiple stresses.
This study is now an international collaboration between the Mittler and Zandalinas laboratories, as Dr. Sara Zandalinas took on a faculty position in Spain.
Investigators at Bond LSC take steps to apply basic research
By Cara Penquite | Bond LSC
Photo by Lauren Hines | Bond LSC
Scribbling in a lab notebook and planning experiments tucked between shelves of equipment, it’s easy to fixate on day-to-day lab operations. But scientists also face the challenge of finding how research can improve the world around us.
“The direction, the vision of the lab, ultimately comes from the principal investigator that bridges the research into applied directions,” said Jay Thelen, biochemistry professor and Bond LSC principal investigator
Despite the focus on basic research within the Bond LSC, many principal investigators choose to take their research to the next level with commercial partnerships.
Thelen’s lab researches ways to increase oil production in seeds and has three patents licensed to Yield 10 Bioscience, a sustainable crop innovation company who applies Thelen’s research to commercial crops. While seed oils like canola and soybean oil are known for their use in cooking, Thelen explains that increased production of these oils could play a larger role in sustainable fuel sources such as biodiesel and sustainable aviation fuel.
“We have to make more oil to balance out our need to eat it [and] our need to wean ourselves off of fossil fuels,” Thelen said. “To do that, we need to either plant more acres of oil seeds, or we have to raise the oil in existing oil seeds.”
Thelen researches enzymes with that potential application in mind. One is acetyl-CoA carboxylase, the enzyme which initializes the production of fatty acid chains found in plant oils.
“We’ve known this is an important enzyme, and we know that any tinkering you do with it has an impact on the oil production,” Thelen said. “In this case we’ve made new discoveries that permitted us to rationally engineer this enzyme to make it more active.”
Thelen suggests thinking of the enzyme as a “gatekeeper” to oil production which initializes the production of fatty acids and increases oil production. Thelen’s lab identified two different gene families that influence the activity of the enzyme in Arabidopsis and camelina plants. Yield 10 then applies these discoveries in other commercial plants.
While Thelen works closely with his commercial partner — having served on their scientific advisory board for three years and now stays in contact with Yield 10’s CEO to develop research projects — some labs stick with short-term arrangements.
Kamlendra Singh — assistant director of the Molecular Interactions Core at Bond LSC and Veterinary Pathobiology research assistant professor — studies HIV treatments. His lab identified a compound licensed by a commercial partner that targets the shell containing the virus’ genetic information.
Singh’s work in HIV started in 1994 with basic research investigating the enzyme that makes the viral DNA.
“I wasn’t into [studying] the drugs when I started working on HIV, I was mostly trying to understand how HIV enzymes works,” Singh said. “Once you know how the enzyme works, then you can target these enzymes for discovering the drugs.”
After years of studying how the enzyme works, Singh switched to HIV treatment. The first step to develop a treatment is to look for structures in the virus that the drug could potentially target to stop the viral replication. Singh targeted the shell around the virus’ genetic information known as the HIV capsid.
Building on previous research, Singh’s lab developed a compound able to bind the HIV capsid and prevent it from releasing the contained genetic information. Even with the licensing of his compound, Singh plans to continue researching ways to improve it.
“There are two reasons to keep working on it. One, well it’s my brainchild,” Singh said. “The second reason is as the company grows, we grow. We get more recognition and more funding. You can use it to [study] different viruses or use the same funding to improve upon it.”
While Singh plans to remain looking towards the applied side of his HIV research, he does not forget his roots in basic research.
“You have to put in time … [to] understand the system first, which is basic science, before you go to applied science,” Singh said.
Michael Roberts, a Chancellor’s Professor Emeritus of animal sciences and biochemistry who has had several patented projects, focuses on improving basic science projects and applies for patents if warranted.
“I don’t deliberately go into anything for commercial purposes,” Roberts said. “If I see something that I think does have commercial application, I’m happy to do it, but that is usually after you do [basic sciences].”
Whether starting a project with applications in mind or focusing on basic research, knowledge gained through research can be building blocks for the future.
“Science is simple. Even the most applied research project has its genesis in basic biology and basic research,” Thelen said.
One step into the Advanced Light Microscopy Core (ALMC) sounds an automated bell prompting Alexander Jurkevich, the core’s assistant director, to step out of his corner office into the open square room. With a friendly smile, Jurkevich coordinates biologists across MU’s campus to reveal the wonders of the microscopic world.
“Our mission is to provide researchers campus-wide with advanced microscopy instrumentation,” Jurkevich said. “We not only provide access to instrumentation, but we also train, advise users and support them during their early research at the core.”
The core hosts an annual image contest celebrates MU researchers’ microscopic imaging throughout the year. After being canceled for the past two years, this year contestants submitted their best images for consideration.
Christie Herd, a postdoctoral fellow in the Alexander Franz Veterinary Pathobiology lab won the Best of Show Award for her image of the La Crosse Virus in mosquito ovaries.
Image by Christie HerdDavid Porciani, assistant research professor under the supervision of Bond LSC’s Donald Burke, won Director’s Award for Best Technically Challenging Image with his image showing epidermal growth factor receptors in two types of resolution.
Image by David Porciani.
Janlo Robil, a graduate student in the Bond LSC’s Paula McSteen lab won Experts’ Choice Award with his image of hormones in a corn leaf.
Image by Janlo RobilA wonderful surprise
Herd was “blown away” when she got her colorful image that won the Best of Show Award. Not only had she tried imaging other viruses with less success, she also worked on different La Crosse samples with no luck.
“That image in particular, I was not expecting to see because the day before I was there for three hours and had to quit,” Herd said. “So, when I saw that image, I was surprised because I did not think I would see that much detail.”
Christie Herd is a postdoctoral fellow in Alexander Franz Veterinary Pathobiology lab. Herd won the Best of Show award for the 2022 ALMC Imaging Contest. Photo by Cara Penquite | Bond LSC
Herd’s image shows the La Crosse virus in developing eggs within mosquito ovaries. Herd uses La Crosse, a type of bunyavirus, as a model to study virus transmission from a female mosquito to her larvae to determine how viruses can remain transmitted within generations of mosquito populations. While La Crosse infects a small amount of humans a year, it transmits quickly, making it the perfect model to learn more about other bunyaviruses like Zika and Chikungunya.
“With bunyaviruses, they’re so multifaceted, and I like being able to research different aspects of them,” Herd said. “I just feel like they’re medically important.”
Herd dissects mosquitoes before imaging. She studies the transmission of bunyaviruses like the LaCrosse and Zika viruses from female mosquitoes to their progeny. Photo by Cara Penquite | Bond LSC
Herd’s image includes different colors to label different parts of the ovaries as well as the virus so she can see where in the ovaries the virus is traveling. Using a technique that allows her to see different focal planes, Herd can see where the virus is in every dimension, but it can be tricky to get high quality images.
“It does require a few hours of playing around, looking at the microscope,” Herd said with a chuckle. “It requires an investment of time, and sometimes there are days where it’s just not what you wanted and it doesn’t work … and you wasted days.”
Even with the challenges, the ability to see multiple dimensions of a sample at once is valuable for research projects like Herd’s.
“You just have to persevere and try again with a new set of samples,” Herd said.
From side project to passion
Although a deviation from his primary research, David Porciani’s project to image cell surface receptors slowly took over his focus.
“The biggest surprise was that I really had fun,” Porciani said. “This was not my primary project, but it became my primary project for a while.”
David Porciani is an assistant research professor under the supervision of Donald Burke. Porciani studies cell surface receptor interactions linked to lung cancer and his image won Director’s Award for Best Technically Challenging Image. Photo by Cara Penquite | Bond LSC
Porciani, an assistant research professor under the supervision of Donald Burke, studies molecules on the surface of cancer cells which are receptors for growth factors. These receptors act as a lock, with growth factors as a key. When the growth factors and receptors come together, the cells divide and create more cells. In lung cancer, there are more of these receptors, which can lead to uncontrolled tumor growth.
“This receptor, EGFR, has been widely studied,” Porciani said. “But for me there is definitely an interest because it’s one of the markers in lung cancer.”
Porciani tags those receptors with small molecules called fluorophores that glow under the light of the microscope, so he can see where the receptors are and how they move. However, the fluorophores cannot attach to the receptors alone, so he used aptamers — synthetic keys created by researchers that can bind receptor locks with specificity similar to the natural growth factors. Ultimately, the aptamers clip the fluorophores to the receptors.
“If you can follow the motion of the receptors, these receptors are kind of dancing,” Porciani said.
In his image, each dot is a different receptor made visible by the attached fluorophore.
However, fluorophores can become bleached, rendering them invisible after being exposed to the laser from the microscope for a while. If the synthetic keys, or aptamers, are still bound to those receptors, they cannot be imaged any longer. To address this, Porciani developed an aptamer which attaches to the receptor for a shorter time and then detaches so that even if the fluorophore bleaches, another aptamer can replace it and so receptors can be imaged for longer time.
“We engineered an aptamer with lower affinity that could work with this approach,” Porciani said. “By having lower affinity aptamers we can still determine localization of a high number of receptors and their motion.”
Porciani shows the process of imaging cells using super-resolution techniques. When a laser hits the cells with the fluorophore specific wavelength, the fluorophores glow while the rest of the cell remains dark, and Porciani can see where the fluorophores, and consequently the tagged receptors are in the cells. Photos by Cara Penquite | Bond LSC
For his winning image, Porciani split the image to show the difference between single molecule resolution on the bottom right and a lower resolution image on the top left.
“With [lower] resolution, you don’t have a single molecule solution. If there are two molecules close together you will see them as just one single dot,” Porciani said. “But with the image, after software analysis with the image on the bottom right, then you have single molecule resolution.”
With this technique — made possible with microscopes at ALMC in Bond LSC — Porciani saw his efforts come together.
“At the beginning, I was just focused on the aptamer engineering from a high affinity aptamer to low affinity aptamer, and making them was the fun part to play with the structure,” Porciani said. “But when we started doing the imaging experiments at the Bond Life Sciences Center I realized that it was not just fun, but it was actually meaningful and this approach could have lots of biomedical applications.”
The artist’s touch
Although passionate about biology and microscopy, Janlo Robil decided to submit his image based on aesthetics.
“I chose this one because I am also a graphic artist, and I appreciate the color and composition,” Robil said.
Janlo Robil is a Ph.D. Candidate in the Paula McSteen lab. Robil studies the hormones involved in corn leaf development. Photo by Cara Penquite | Bond LSC
Robil’s image shows a developing corn leaf with different colors labeling different plant hormone response proteins involved in stimulating growth. His unique image of an entire leaf, which is just under a millimeter in length, required piecing together images of sections of the leaf.
“About 0.75 millimeter, that’s still big in the microscope,” Robil said. “This is kind of difficult to make because it means that you need to tile several images [together] and sometimes it takes up to an hour just to [get] an image.”
The experiment requires planning ahead since the plants containing the fluorescent proteins must be crossed with plants with genetic mutations to determine the roles of the hormones in the leaf development.
To tag the plant proteins with fluorescent proteins requires planning ahead since the plants must be grown with genetic mutations.
“The beautiful image is actually a result of the expression of fluorescent proteins that are tagging the hormone response protein and also the hormone transport protein,” Robil said.
Robil looks at images from a confocal microscope. Using a laser, confocal microscopy brings clarity to Robil’s images. Photo by Cara Penquite | Bond LSC
Initially from the Philippines where the agricultural staple is rice, Robil came to Mizzou interested in genetic mechanisms to make rice plants more productive. One way to enhance the rice plants is to make the rice leaves more similar to corn leaves, so Robil found interest in the McSteen lab’s project understanding the role of hormones in corn leaves.
“This project is perfect for me because I am studying the leaf and also integrating genetics,” Robil said. “And I love microscopy so much. I had quite a good amount of training starting in 2021 on confocal microscopy, and that’s why I was able to image this.”
Mengran Yang sat perched on a stool too tall for the cart of lush green tobacco plants in front of her. Behind towering shelves of lab equipment, she hunched over the plants and steadily pricked each leaf with a syringe.
Yang works with Arabidopsis and tobacco plants to learn about plant immune systems as a postdoctoral fellow in the Gary Stacey lab. Her research focuses on signals plant cells send to coordinate a fight against pathogens.
“I think it’s very interesting to see how plants can defend against the pathogens,” Yang said.
Mengran Yang infiltrates the leaves of tobacco plants with a syringe. While her work mostly focuses on Arabidopsis plants, Yang also uses tobacco plants as a tool in her research since it is convenient to express the correct target proteins in their leaves. Photo by Cara Penquite | Bond LSC
Just like humans have immune cells that fight germs, plants have a network of cells and signals to deal with harmful microbes. This system is particularly important for plants since they are rooted in place and cannot avoid the attackers in their environment.
The plant immune system protects it both inside and outside its cells. Proteins inside the cell can recognize molecules from invaders and trigger an immune response, and the second — the part Yang’s research focuses on — uses receptors on the surface of the cells to recognize molecular patterns from microbes to signal for the plant to get rid of the pathogen.
“Our lab is focused on the extracellular ATP signaling pathway,” Yang said. “ATP, as maybe everyone knows, is an energy source, but we found it can also be a signal when it is released to the extracellular matrix, where it is referred to as extracellular ATP.”
Yang’s work with the lab started when she moved from China to Columbia for her postdoctoral research at Mizzou. Although originally drawn to the lab because of Stacey’s prominence in the field of plant immunity and signaling, Yang stays because of the community within the lab.
“Our lab is very international — some people are from China, Korea, Brazil, Vietnam and India,” Yang said. “A lot of the same-aged girls will go out for fun.”
This community stems from Stacey’s emphasis on the team’s collective success.
“You try to develop an esprit de corps in the lab where people care about each other’s success,” Stacey said. “They’re taking care of themselves, but at the same time, they care about other people’s success.”
Becoming a good researcher started with strong academics, and Yang remembers being the top of her class in biology, physics and math in middle school and high school. When she started her studies at the university level she followed her growing interest in biology.
Growing up with her twin sister in China, Yang recalls societal pressures to fill any spare time with more study. Her parents thought her teachers gave too much homework and pushed back on this expectation.
“My father thinks this kind of education is not good, he thinks you need to promote your efficiency and not just work hard,” Yang said. “You need to study smart, not just hard, and I think my dad influenced us a lot.”
Yang applies this mentality to her research and is supported by Stacey who encourages her to plan experiments and life goals.
“While I was a Ph.D. student, I spent the most time in the lab for fun,” Yang said. “But now I’m good at scheduling stuff, so I schedule my experiments at least a week ahead.”
Mengran Yang shows a dish with Arabidopsis plants. Yang’s work primarily focuses on studying extracellular ATP in Arabidopsis plants. Photo by Cara Penquite | Bond LSC
Stacey works with Yang to ensure her future impact as a researcher. When picking a project, Stacey guides his researchers towards projects with lots of potential.
“That’s the kind of discussion I have with people, what’s the best project for them where they have the chance to make an impact,” Stacey said.
With her lab mates and other research labs, Yang collaborates to strengthen each other’s weaknesses. If she does not have experience with an experiment, Yang asks other postdoc students with more experience for help with her project. When she publishes her research, she makes sure to give credit to the other students who helped her.
“In Chinese, ‘shuangying’ means ‘good to both sides,” Yang said. “That’s very common. You will read a paper, and you can also see most [papers] have a lot of authors there. That’s the cooperation.”
After finishing her research in the U.S., Yang plans to return to China to continue doing what she loves — research.
“I want to have my own lab in China,” Yang said. “It’s difficult, I know, but it’s my dream.”
Exploring new places and diving into the world of the unknown can be intimidating. At a young age, Leah Lepore was immersed in this world and grew to love it.
“The first time I left the country was to travel to Japan and it was an incredible culture shock,” said the current Chris Lorson lab member. “From my twelve-year-old perspective, I was learning about a different way of life but also drove my parents nuts because I would only eat McDonald’s while we were there.”
An avid traveler, Lepore loves immersing herself in new cultures and seeing the world from a different point of view. This has blended into other areas of life, especially when it comes to her passion for science.
“I think traveling is what formed this kind of wanderlust that I have, and that exploring unknown places gets you out of your day-to-day routine and puts things into perspective,” she said. “There’s so much in the world than what you see around you.”
Lepore is a sophomore majoring in biochemistry. She wasn’t new to working in a lab when she joined Bond LSC in summer of 2021. She worked at two other labs in high school, so she found it imperative to join a lab that would challenge and prepare her for the future. As a member of the Lorson lab and an employee of Shift Pharmaceuticals — Lorson’s business off-shoot of his research — she found that.
“It’s really interesting to see the industry science and the academic science be complimentary,” Lepore said.
At Shift Pharmaceutical, she works on Charcot-Marie-Tooth disease (CMT). CMT causes abnormalities in the nerves feet, legs, hands, and arms. This disease was unfamiliar to her before she joined, but that did not hinder her enthusiasm to learn more.
“What’s really interesting is that it doesn’t necessarily kill you, but it diminishes the quality of life because it is caused by this overexpression of protein,” she said. “It causes your limbs to contract but not able to relax while also impacting your balance and dexterity.”
Lepore uses gene silencing therapy with synthetic nucleotides that bind to mRNA in this research. mRNA codes for proteins and since there is an abundance of certain proteins in patients with CMT, she is trying to silence portions of mRNA that code for them.
Lepore aims to spread her desire to be involved in research as an ambassador for the Office of Undergraduate Research, and she encourages students to get involved as soon as possible. Many students are apprehensive to dive headfirst into working at a lab, but Lepore reassures that there is a place for everyone at Bond LSC.
“I find that everyone that I’ve met here is extremely intelligent, but also great at making anyone who hasn’t worked in a lab before feel extremely comfortable,” she said. “It’s a very welcoming and inviting atmosphere.”
When not in the lab or helping undergraduates, she focuses on fitness. At Orange Theory, Lepore lifts weights and runs on the treadmill, which helps her cope with stress and anxiety. No matter how hectic life might get, her positive attitude and ambitious personality shine through.
“Sometimes you have to realize that you’re not going to know everything even if you want to, but there are always going to be people that are willing to explain it to you,” she said. “However, not knowing everything is okay sometimes because it gives you room to learn and engage these critical skills that are not only going to help you in the lab but also in your day-to-day life.”
Hari Krishnan holds a handful of A. pavonina seeds. Known for their bright color, the seeds are known among many Asian and African communities as coming from the red bead tree. Photo by Cara Penquite | Bond LSC
By Cara Penquite | Bond LSC
An energetic and fulfilling day starts with a spread of healthy meals, and many people rely on nutrition labels to meet their daily quota of vitamins and nutrients. But how did scientists measure the Vitamin C in an orange or the protein content in peanuts for the label?
Finding out what is in food we eat starts with scientists like Hari Krishnan, a USDA-ARS molecular biologist and MU adjunct professor of plant science and technology. Krishnan calculated the type and degree of nutrients packed into seeds from red bead trees with the help of the Advanced Light Microscopy Core in Bond Life Sciences Center.
“We are highly dependent on the food that we eat,” Krishnan said. “Anything we can do in order to either improve nutrition or quality or finding alternative sources of food is very useful.”
Commonly known for its pods of seeds as bright as red M&M’s, the red bead tree is known as Adenanthera pavonina in research communities.Krishnan took an interest in A. pavonina seeds — turning away from his usual soybean research — to see if they could be a potential alternative protein source in developing countries. He quickly found a different, unusual characteristic.
“I’ve never seen a seed have such a high content of trypsin inhibitor,” Krishnan said.
Our bodies make trypsin to break down protein in our intestines, but trypsin inhibitors block the enzyme from its job of protein digestion. That makes it hard for us to benefit from nutritious proteins in the seeds. Although many Asian and African communities already incorporate A. Pavonina seeds in their diet, its unusual amount of trypsin inhibitors limits nutritional benefits.
“Soybeans have probably less than five percent of the entire seed protein made of trypsin,” Krishnan said. “This particular legume is 20 to 25 percent, which is fairly very high.”
Krishnan turned to Alexander Jurkevich, associate director of MU’s Advanced Light Microscopy Core, to find out where in the plant’s cells the trypsin inhibitors were located. Jurkevich and Krishnan used glowing molecules to mark the trypsin inhibitors and see where they are stored in the cells.
Hari Krishnan sits in his lab at MU Curtis Hall. A USDA-ARS molecular biologist and MU Adjunct Professor of plant science and technology, Krishnan’s research looks at the nutritional value of legumes. Photo by Cara Penquite | Bond LSC
Tagging protein here starts with an antibody. The first antibody acts like one side of a strip of velcro that can attach to a second antibody that also carries a molecule of a fluorescent dye. Through the double antibody system, the glowing, fluorescent flag attaches to show scientists which parts of the cell have trypsin inhibitors.
While Krishnan developed the antibody, Jurkevich used his expertise in light microscopy to take images of the glowing cells.
“This cooperation is very important, because modern research technologies are very complex and a single person cannot learn and excel at all techniques available in life sciences,” Jurkevich said.
Understanding the amount and locations of trypsin inhibitors, Krishnan looked to reduce inhibitors so the seeds would be more nutritious for humans.
Roasting or boiling the seeds breaks down the trypsin inhibitors, but Krishnan warns that it may break down other essential amino acids as well. In his work with soybeans, Krishnan looks for a way to grow plants without trypsin inhibitors at all.
“We were able to find some [soybean] mutants, which have lower levels of this trypsin inhibitor,” Krishnan said.
Natural mutants with lower levels of trypsin inhibitors could be cultivated on a larger scale to produce seeds that are easier for humans to digest.
Since trypsin inhibitors are not ideal for consumption, Krishnan decided to think outside of the box. He turned to USDA-ARS research scientist and entomologist Adriano Pereira to find another use for the seeds.
Pereira tested the seed proteins as an insecticide against corn rootworm larvae and found that it stunted larval growth but did not necessarily cause mortality. While it is still early in this research, there may be some insecticidal properties from the seed.
“It’s something that has to be investigated to make sure […], but we assume that since it is a trypsin inhibitor it could be inhibiting on some level the trypsin during the growth of the larvae,” Pereira said.
As Krishnan’s first look into A. pavonina seeds, the research opened many new questions yet to be answered, but he plans to continue investigating the role of trypsin inhibitors in soybeans and other plant protein sources.
“[Research] is a never-ending investigation, and one thing leads to another. It’s always interesting,” Krishnan said. “I come to the lab everyday thinking of what I’m going to end up doing today.”
The Advanced Light Microscopy Core provides technical imaging expertise to researchers who need state-of-the-art imaging for their experiments. That includes confocal, super-resolution, digital light-sheet and widefield microscopes, image analysis and processing and sample preparation.
Growing up in a humble beach town in China, Aijing Feng dreamed of following the footsteps of her idol and Microsoft co-founder Bill Gates. Now halfway around the globe nimbly tapping a keyboard in her cubicle at the Bond Life Sciences Center, she realizes the shortcomings of her tech-giant fantasy.
“For a commercial thing, you can have lots of money, you can earn lots of money, you can have [a] great life,” Feng said. “But when you [do] research, you can have ideas [that] something can change in your life. That might be awesome.”
Feng — a budding postdoctoral researcher in the Henry Wan lab — works tirelessly to find answers to her questions. Feng once attached cameras as a bioengineering Ph.D. student, to a drone to determine which plants in a field were under stress, a method that could help farmers know which portions of a field are unhealthy.
“We were trying to use technology to automatically detect and then tell humans how much water [plants] need and what environments influence the plant’s growth,” Feng said.
The colorful drone images show researchers the plants’ temperature, height and color. These factors indicate a crop’s health and nutrient supply so farmers can determine which areas of the field may need replanting or additional care. Feng integrated the drones with sensors and created software to stitch images of the field together to see it as a whole.
“I really enjoyed working with her because she can get things done,” Feng’s former mentor and principle investigator Jianfeng Zhou said. “Let’s say we have a paper we need to revise, she may finish within a couple days, but other people may need to take a couple weeks. She’s really hard-working.”
Even as a teenager, Feng knew she wanted to spend her days with fingers flying over a keyboard, and she attended South China Agricultural University in Guangzhou as a computer science undergraduate and master’s student. The starting point of her research soon blossomed friendship when her master’s advisor paired her with an undergraduate named Jian Liu.
Their minds working together pulled their hearts closer as well, and the two fell in love while working on lines of code. Now married, the couple lives in Columbia with their six-month-old daughter balancing family life alongside studies.
“It’s hard to balance, you just need to decide what you have to finish today or this week and what work you can delay,” Feng said.
Feng feels at home in Columbia preferring the small-town pace to the busy streets of Guangzhou. Dipping a toe into Mizzou’s resources, she starts her mornings swimming at the MizzouRec after taking her daughter to daycare.
She recalls days at the beach with her father trying, unsuccessfully, to teach her to swim through the rolling ocean waves. When she moved to Columbia it took a joint effort among her friends for her to learn, but now she incorporates a swim into every day.
“For years my father came to me and I could never learn,” Feng said. “One of my friends and my husband [taught me]. At the time I was a Ph.D. [student] and swimming was what I loved.”
In the afternoon, Feng delves into her research in the Wan lab at Bond LSC. Feng analyzes genomic data for the lab with the goal of developing broadly protective vaccines for various pathogens, such as influenza, which causes both seasonal and pandemic flue outbreaks in humans, and E. coli, which causes an illness in poultry.
“She’s doing computational biology to learn how diverse among pathogens at both genetical and antigenic levels and understand their risks to human and/or animal health, and then develop AI tools to design broadly protective vaccines for these diseases,” Wan said.
Wan recognizes Feng’s work ethic up close.
“She seems really passionate, and she works extremely hard,” Wan said. “She learns things quickly, and she is also a good communicator.”
Turning her hands over in rhythm with her light conversational voice, Feng is as personable as she is intelligent and values working alongside advisers.
“Each of my advisors taught me many things,” Feng said. “How to do research but also how to face your life, how to balance your life, how to schedule and manage your work and your life. They are very important people in my life.”
While still uncertain about what the future holds, Feng plans to remain in research rather than using her computer skills in the commercial world.
“I just care about coming up with good ideas and what makes me excited,” Feng said.
The Baker lab poses for a group photograph. The lab has been working with specialized pro-resolving lipid mediators in efforts to help patients with Sjögren’s Disease. Photo by Karly Balslew, Bond LSC
By Karly Balslew | Bond LSC
Saliva is probably not the first thing that comes to mind when we think about eating our favorite foods. The clear liquid washes away food debris and bacteria, and it plays a vital role in maintaining our dental hygiene and oral health.
You may take it for granted, but for patients with Sjögren’s disease, life without saliva is challenging.
“We’ve seen firsthand how patients suffer from Sjögren’s disease and what the consequences are in the oral cavity,” said Olga Baker, a Bond Life Sciences Center principal investigator studying the syndrome.
The autoimmune disease causes our body to attack the glands that produce tears and saliva. This destruction at the hands of our immune system causes dry mouth and dry eyes as it eventually kills the cells that perform this valuable service to our bodies. Without saliva, tooth decay and painful diseases like gingivitis are almost inevitable.
Sjögren’s disease affects approximately 4 million people in the United States. The severity of the disease varies in patients, but it destroys all exocrine glands and there is currently no cure. While the cause of the disease is still unknown, researchers are turning efforts to alleviate patient discomfort.
The Baker lab focuses on a class of drugs called specialized pro-resolving lipid mediators. These medications are derived from essential fatty acids and play an important role in decreasing inflammation and recovering salivary function.
Harim Tavares Dos Santos — a post-doctoral fellow in the Baker lab and lead author on a recent study of this drug —has seen success with restoring salivary functions with the specialized pro-resolving lipid mediator drug resolvin D1 (RvD1). Resolvins act as anti-inflammatory mediators and restores saliva flow rates. The lab will test a variety of drugs from the specialized pro-resolving lipid mediators’ class to see which one would yield the best results, but some receptors they affect within the salivary glands are unknown.
“The first step is to see if we know all the receptors for other drugs,” Tavares Dos Santos said. “Then, we test the different drugs to see which ones activate the receptor to possibly decrease inflammation and reach the goal of getting the saliva back.”
RvD1 activates the receptor ALX/FPR2 Tavares Dos Santos explains. This then triggers a signaling mechanism that promotes the survival of salivary gland cells and protects the cells tight junctions while increasing saliva secretion. Researchers used six human minor salivary from female subjects in this experiment to determine the expression of pro-resolving lipid mediators in patients with and without Sjögren’s syndrome.
Previously, the lab tested these drugs on mice models with Sjögren’s-like features and saw they can recover salivary function. However, researchers need more data to find other receptors that can maximize the positive response from the drug.
But mice aren’t the same as humans, and even when researchers test on humans it can be difficult to find patients with Sjögren’s disease willing to participate in the research.
“We don’t have a lot of literature in salivary glands to look for. Basically, what is known about resolvins and salivary glands is generated here in the lab,” Tavares Dos Santos said.
“Another challenge is that no one knows what causes the disease, so the research is mainly trial and error,” Baker said.
Baker explains that studies show people with Sjögren’s disease could have a genetic predisposition for it, but there are also environmental factors like viruses that could trigger the genetic components that lead to Sjögren’s disease.
“In the end, we want to create a drug that has all those properties to cure the patient so hopefully in the future, we can get a product on the market,” Baker said.
The Baker lab will present their progress with Sjögren’s syndrome at the 2023 Gordon Research Conference in Ventura, California. Both Baker and Tavares Dos Santos will co-chair the international conference that attracts researchers studying salivary glands and exocrine biology.
“This is a very important conference that will elevate Missouri,” Baker said. “The whole thing is really exciting.”
Olga Baker is a professor of Otolaryngology-Head and Neck Surgery and Biochemistry as well as a Bond Life Sciences Center principal investigator. Harim Tavares Dos Santos is a Bond Life Sciences Center post-doctoral fellow.
Data connects all: ‘Champion collaborator’ Xu bridges research disciplines with bioinformatics
By Cara Penquite | Bond LSC
Dong Xu extracts wonder from numbers with a keyboard and eager teams of scientists at his fingertips.
With his salt-and-pepper hair visible above the cubicle walls and his voice softly but steadily articulated, the beauty of bioinformatics takes shape in his mind although it might not be inherently evident in the rows of computers tucked into a small first floor lab.
Xu weaves a multifaceted masterpiece of research methodologies and makes sense of a sea of data from cell biologists, plant scientists, engineers and many more with hundreds of publications to show for it.
“For research, collaborating is key because the nature of research requires many views, skills [and] knowledge,” Xu said.
A Bond Life Sciences Center researcher and a newly endowed Curators professor of bioinformatics in the School of Engineering, Xu harnesses data to better understand biological systems such as revealing a better picture of protein dynamics or analyzing genetic codes for individual cells. With advanced data interpretation and machine learning, the Xu lab opens opportunities for more in-depth research across Mizzou and the world.
With so much existing on a microscopic level in living creatures and new technologies to collect data continually evolving, massive amounts of information are extracted in biological research. Xu’s expertise is invaluable to interpret massive amounts of information, but he takes it a step further predicting how pieces of biological systems interact.
His recent efforts include using deep learning — a subset of artificial intelligence and machine learning — to understand how the shape of protein binding sites change when molecules bind to other areas of the protein. This research, recently published in Nature Communications, and represents one of many collaborations the Xu lab is known for — in this case with Jilin University in Changchun, China.
The Xu lab’s help is crucial to researchers whose specialties lie in biological systems rather than computer science. Bond LSC Director Walter Gassmann, recognizes Xu’s niche.
“Biology has become so complex that you can’t be expert in everything,” Gassmann said. “The way to move forward is to collaborate with people, and that’s what Bond LSC is all about — bringing people with different disciplines under one roof, letting them rub shoulders and figuring out how best to solve a problem.”
With computational analysis being key to many research studies, the Xu lab collaborates with various labs at the research center.
“Dong is the champion collaborator [with] so many connections in the center,” Gassmann said.
Xu makes note of the particular importance of working together when mentoring young researchers. Students in the Xu lab work in teams and alongside biologists, allowing the researchers to learn from one another.
“There is actually an African saying, ‘it takes a village to raise a child,’” Xu said. “The same is true for mentoring students. It really takes many people to mentor a student. That includes not only community members and collaborators, but also peers.”
Xu fosters that shared work ethic by giving credit where it is due when it comes to research. While other institutions sometimes only give the lead investigator full credit for a project, Mizzou recognizes the work put in by each collaborator for any given project.
“MU is a very collaborative environment,” Xu said. “It really supports interdisciplinary research, [and] I don’t take it for granted. Interdisciplinary research usually relies on administrative support.”
Bioinformatics was more of an afterthought to Xu despite its prominence in his life now. His studies started with bachelor’s and master’s degrees in physics, and it was not until he started Ph.D. studies that his focus shifted.
“I was working on the biophysics of saturated proteins, and that’s a computational analysis,” Xu said. “I became very interested in computational work, so since then I’ve been working on this computational biology, or bioinformatics, for about 30 years.”
Xu’s drive to know all things data is revealed in his excitement to talk science.
With a small chuckle he noted that research does not usually bring money and fame. While he could use his computer skills to gain such rewards working for tech companies, he chooses to pursue science instead.
“To be a scientist requires passion,” Xu said. “You really need passion and to believe in the impact, the value of research. I do feel a reward in that regard.”
The Xu lab develops machine learning, a subset of artificial intelligence that involves teaching computers to mimic human intelligence. That starts with developing technology to collect data and facilitate its analysis.
This stretches into deep learning, more advanced machine learning that involves layers of neural networks. The input information is organized through these networks as the computer makes sense of the information.
People encounter deep learning in their day-to-day lives. The algorithm that sorts photos by faces in your phone’s photo app — that’s deep learning.
“It can start from these pixels and then can retrieve information like eyes [and] nose, and then can [find] a match,” Xu said. “It’s not only deep layers, but also the complex architecture of the network, so that’s why it’s called deep learning.”
A similar process is used in the Xu lab’s work. Rather than sort pixels to recognize faces, Xu’s work sorts data — like amino acid sequences — to predict protein interactions.
By finding trends in large sets of data, deep learning can speed up existing processes.
Mark Hannink, a Bond LSC principle investigator, recently saw this in action. Xu developed techniques to read scientific articles and generate diagrams of protein pathways described in the database. While people can read and summarize these articles, the process takes time and leaves the latest of the diagrammed pathways outdated.
With deep learning, each time a new article is published, the diagram could automatically update.
Working closely with Xu, Hannink saw his mentoring approach in action.
“What I’ve been impressed with is how good of a mentor he is to the students working on this project,” Hannink said.
While high-impact research is one goal, Xu also takes care to develop scientific minds.
“Not only [do] we produce papers [and] software, we also really need to produce high-quality, next-generation researchers,” Xu said. “So, our goal is to mentor people to be successful, and many of our lab members are really on the right track to be successful.”
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