Lauren Hines

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#IAmScience Toshi Ezashi

December 4, 2020 By Lauren Hines in #IAmScience Tags: placentas, stem cells

By Lauren Hines | Bond LSC

Despite his quiet demeanor, Toshi Ezashi leaves an impression on those who meet him in the halls of Bond LSC through his quiet intensity and constant courtesy.

The research professor was here before the “Joy of Discovery” sculpture in the atrium was built or the living plant wall was hung, calmly making progress with stem cells as part of the Mike Roberts lab team.

“I’m mainly doing research on trophoblast that compose the main component of the placenta tissue,” said Ezashi, who first came to Mizzou in 1995. “Using stem cell technology, we try to understand the pregnancy disease which happens in the placenta.”

Stem cells can be considered the ultimate source. They turn into all different types of the adult cells that make up the many tissues, organs and parts of a living thing. Induced pluripotent stem cells, on the other hand, are a little different. They start out as adult skin or blood cells but are pushed to revert back to an embryonic-like stage where they can once again turn into about any type of cell and self-renew.

Induced pluripotent stem cells were first discovered in a paper that appeared in Cell in 2006, and Ezashi excitedly presented it to his lab mates that same day.

“He knew instantly how important that was going to be,” said Laura Schulz, associate professor of Obstetrics, Gynecology and Women’s Health who works with the Roberts lab. “That’s just him. I think he really sees those things.”

Schulz has worked with Ezashi for the past 15 years.

“He’s just an incredibly kind person, but also a really very thoughtful, thorough and creative scientist,” Schulz said. “So, together those have made him a great collaborator.”

Currently, Schulz and Ezashi are studying trophoblast cells — stem cells from the placenta of early pregnancies. Ezashi is using these trophoblast cells to try to eventually understand preeclampsia, which results in dangerously high blood pressure and almost a rejection of the placenta. It is a potentially fatal complication that is only cured by the premature delivery of the baby.

Studying the placenta is difficult due to ethical issues and its ephemeral nature in relation to pregnancy. However, Ezashi generates placental cells that derive from umbilical cords left over after pregnancy to study the early stage of the placenta. This way, Ezashi and other researchers can figure out what causes the pregnancy complication.

“Right now, we don’t have any way to cure this disease,” Ezashi said. “The only option is to deliver the baby prematurely. Because of this issue being rooted in our lack of information of the time of the period, how the placenta works, we are expecting this study to provide important information to understand why this disease develops in this case.”

Ezashi has seen attitudes towards this kind of research shift in his many years working with stem cells.

“It was 2002,” Ezashi said. “We had this type of way of thinking that was just application. In those days, there was some understanding or social acceptance of stem cells, but we stepped forward to using stem cells in this field. I look back more than 17 or 18 years ago, but I still think it was the right move and decision to get into this field.”

Ezashi has grown along with attitudes and Bond LSC.

“He’s gained confidence and leadership skills I think over those 15 years, but actually he seems very similar to the person I met 15 years ago,” Schulz said. “He’s really just kind of a down-to-earth, quiet guy and the same careful scientist he’s always been.”

Even with 25 years under his belt, Ezashi isn’t leaving Bond LSC anytime soon.

“I know I have a different background, but by staying here to do something, I can uniquely contribute to society,” Ezashi said. “That means something. I can be a part of some message to the work, ‘How much can we achieve?’”

Bad Boys of Biology Turned Good

November 17, 2020 By Lauren Hines in Research Tags: reactive oxygen species

Yosef Fichman, post doctorate fellow in the Mittler lab, walks through how the lab uses arabidopsis plants for certain experiments. | photo by Lauren Hines, Bond LSC.

By Lauren Hines | Bond LSC

Shaking a bad rap can be hard.

However, the Ron Mittler lab at Bond Life Sciences Center has shifted the scientific community’s thinking from seeing reactive oxygen species (ROS) as destructive to vital.

“It’s always a challenge when you do something for the first time, and people don’t always believe you,” said Mittler, principal investigator. “They want you to prove it.”

ROS are reactive molecules that perform chemical reactions easily. While these molecules cause destruction in cells with these reactions, they can also send widespread messages and regulate many essential processes. However, this benefit of ROS wasn’t always known.

Back in the Day

In the 1980s, the scientific community recognized ROS as important. But according to Mittler, the community also thought ROS only offered destruction to human cells and caused aging.

“All this is not true,” Mittler said. “It’s not that simple to just say that, but there was a big hype about reactive oxygen species being painted as the bad boys of biology, and so forth.”

Then, in 2009 Mittler discovered the ROS wave.

This wave fills in the communication gap in plants left by the lack of something like a central nervous system. Instead, plants use the ROS wave and systemic signaling to respond to stresses. ROS triggers a cell reaction in one area of the plant that triggers the cell next to it and so on creating a wave of activation throughout the plant. This way, the plant can acclimate to its environment and is important since plants don’t have the luxury to get up and move when something threatens them.

Mittler was at the University of Nevada in Reno studying responses to ROS. He was originally looking to develop a reporter system to screen for mutants that are deficient in sensing ROS.

“We noticed that we don’t only record local responses that when we treated one single leaf, we got a systemic response, and, from there, using additional experiments, we developed the ROS wave concept,” Mittler said.

Mittler published his new discovery in Science Signaling, and more papers came, exploring systemic signaling and similar processes, highlighting the importance of the ROS wave to many biological responses.

“Slowly people started to realize that reactive oxygen species are actually important, and they’re doing a good thing,” Mittler said.

What’s Happening Now in the Lab

More than 10 years down the road, Mittler still focuses on ROS. Current Mittler lab post doctorate fellow Yosef Fichman, has taken the baton in the study of ROS waves.

“I was born to a family that was working in agriculture, and my father grew oranges in Israel,” Fichman said. “For a farmer or a person working in agriculture, life revolves around growing plants 365 days a year. In a way, I was always fascinated by plants.”

Fichman and others in the lab have been working towards finding more pieces to the process.

“There is a cliché that says proteins never work alone, so we’d like to know which other ingredients are involved,” Fichman said. “In my latest paper, using mutant plants, we were able to detect more ingredients to this mechanism and expand our knowledge.”

Fichman and others in the Mittler lab worked to image the ROS wave, tested different stresses for the ROS wave to respond to and found more pieces to the puzzle. Fully understanding this process can help researchers eventually create genetically modified crops that withstand more stresses.

What There’s Left to Discover

Currently, researchers don’t know exactly which compartment of the cell is most important in regulating this process or if compartments interact with each other. They also don’t know how it all results in gene expression or how different waves interact with each other and work together.

“There’s a lot to learn because we know that if we just look at this from the narrow window of the ROS wave, we know that it’s important,” Mittler said. “If you don’t have the ROS wave, the plant cannot acclimate properly.”

Though Mittler lab researchers have been hard at work for the past few years dissecting this process, it’s unlikely they’ll stop anytime soon.

“In a way, it’s harder to publish new ideas, but it’s more exciting,” Fichman said. “We are grabbed by our curiosity and we want to find the answer. We want to find the big answers.”

Find more details about Mittler’s current research in the most recent publication found in the Plant Cell journal.

Unknown Origins

November 9, 2020 By Lauren Hines in Research Tags: NASA, RNA

$5 million grant awarded to study RNA’s place in start of life on Earth

In his lab at Bond LSC, Donald Burke-Agüero examines his model of the RNA protein structure. | Photo by Lauren Hines, Bond LSC

By Lauren Hines | Bond LSC

The search for life on other planets may seem quite literally out of reach, but the search actually starts here, on Earth.

“Something that guides people in thinking about how life might come about on other worlds is trying to understand how life might have started here on this planet,” said Donald Burke-Agüero, principal investigator at Bond Life Sciences Center and professor of Molecular Microbiology & Immunology in the MU School of Medicine.

The Burke lab recently won a $5 million Interdisciplinary Consortium for Astrobiology Research (ICAR) award from NASA in partnership with eight other institutions. The award will fund their proposal to study RNA as a model for the origins of life.

Scientists hypothesize that RNA, a nucleic acid, was at the heart of molecular processes when life started around 4 billion years ago. RNA is like DNA in that it is a set of instructions and can store genetic information about basic building blocks for life, but it can also perform chemical reactions like enzymes. These two functions help speed up reactions to make important molecules needed for life.

“Becoming part of this has been over 20 years in the making for me,” Burke said. “It’s a theme that I care about tremendously, which is providing a really solid experimental foundation for some of the speculation about how life may have started.”

Burke found out about the grant while he was in another zoom meeting.

“I went back to the meeting and said, ‘Guys, I can’t stay. I’m not paying attention to anything you’re saying right now. Have fun. I’m bouncing off the walls,’” Burke said.

The predecessor to the ICAR program was the NASA Astrobiology Institute, which first called for members in 1998. Burke was starting his first faculty position back then. He always wanted to be a part of it, but it never quite worked out until now.

The “RNA World Hypothesis” has intrigued and driven scientists since the 1960s but has been increasingly explored in the past three decades as technological advances have allowed scientists to look for evidence to support it.

“Part of being in the origin of life team is working with RNA and to expand its known limitations,” said Jordyn Lucas, a Ph.D. student in the Burke lab. “We also like to explore how various modifications could make RNA better at doing a specific job, or how can it make it more durable under certain conditions.”

While RNA can make some reactions, it is possible that a certain set of modifications, tools or conditions could push RNA to perform more like an enzyme. This grant will help the Burke lab find those conditions if there are any.

“It’s kind of like a tool,” Lucas said. “It’s like if I gave you a piece of paper, asked you to write an essay, but I didn’t give you a pen. You can’t do it. It’s not because you don’t have the ability to do it. You just don’t have the right tools.”

Those tools can be hard even for humans to access.

A tube the size of your fingertip can contain quadrillions of RNA molecules and therefore quadrillions of sequences. That’s not an exaggeration. You can imagine how difficult it would be to sift through all that by testing them one by one. It wasn’t until in vitro evolution — a method that screens through large amounts of nucleic acid sequences — in the 1990s that scientists could explore many questions about RNA. Even with that, today’s technology is limited.

“Part of what this grant is going to do is attack that problem to try to specifically do the things that have been technologically very difficult,” Burke said.

The aim of the proposal is to push the limits of what RNA is capable of doing. These findings could bring the RNA World theory closer to being an established fact. This would help NASA know what conditions to look for life on other planets.

The technological advances from this project will also have implications for synthetic biology applications like biomedicines and biofuels. The goal is to find ways in which parts of modern biology can be replaced with RNA that can do something similar.

“Obviously, understanding our place in the universe and how we came about is a big deal and would be a societal benefit, but also a tangible thing that helps somebody be healthier,” Burke said. “That’s important too.”

Further exploring RNA brings us one step closer to a model of the origins of life on Earth and even life on other planets.

“We have no idea how likely life is,” Burke said. “If we can help demonstrate some of the ways that life comes into existence, it will really help to understand how many neighbors we might have on other worlds. And whether we’re likely to have any neighbors at all.”

Institutions involved in the proposal are the University of Missouri in Columbia, St. Louis University, Purdue University, University of Southern Mississippi, University of California in Irvine, University of California in San Diego, University of Washington in Seattle and University of California in Los Angeles.

NASA Selects New Science Teams for Astrobiology Research

Shining Light on Plant Reaction

November 5, 2020 By Lauren Hines in Research Tags: plant signaling pathways, reactive oxygen species

Arabidopsis grows in Ron Mittler’s lab. | photo by Becca Wolf, Bond LSC

By Lauren Hines | Bond LSC

Daylight might not seem dangerous, but for plants, too much daylight can cause hazards similar to a nasty sunburn or a human scalding themselves.

When you jerk your hand back from a boiling pan or a hot faucet, in a millisecond electrical signals are sent up your arm to tell your brain to move away. Like this reaction, plants have their own protective reactions to too much light.

“I think what you need to understand is that plants can’t survive without light,” said Ron Mittler, principal investigator at the Bond Life Sciences Center. “Light is the master of the plant basically.”

Mittler’s lab discovered that light receptor phytochrome B is responsible for triggering the signals for light danger that reverberate from one cell to another and not chloroplasts as previously thought. Understanding how plants respond can help build a picture of a process called systemic signaling to help researchers create genetically modified crops to withstand these stresses. Their results were recently published in the Plant Physiology journal.

The scientific community thought if light was put on a plant, the organelles that conduct photosynthesis, called chloroplasts, would trigger systemic signaling and the ROS wave.

“It’s really about having this spreadsheet of knowledge and not knowing where the pieces of the puzzle from high light-reactive action to chloroplast or to stomatal closure, where all those pieces fit,” said Mannie Liscum, collaborator and Mizzou professor of biological sciences.

The ROS wave, named by Mittler in 2009, is the process where reactive oxygen triggers a cell reaction that subsequently triggers the cell next to it and so on creating a wave of activation. Reactive oxygen is a tricky molecule that reacts very easily. It can cause destruction in cells with these reactions or use its reactivity to send a message in a proactive way between many cells.

“What we found is that if we use a phytochrome mutant — phytochrome B in particular — we completely eliminate this ROS production by high light stress,” Mittler said. “To me, it was really amazing because everybody else thought that the light would impact the chloroplast.”

While chloroplasts absorb light to turn into energy, phytochromes can take certain types of light and turn genes on. Depending on the type of phytochrome, they can take in different wavelengths of light and help plants understand light intensity and light quality. In turn, this helps a leaf or a stem figure out where to grow and if light is coming through shade.

The Mittler and Liscum labs used the sensitivity of the light sensor to their advantage.

“By using different wavelengths, different colors of light, we started narrowing down which of the sensory systems in the plant were actually doing the job,” Liscum said.

Eventually, they found responses to red light. This meant that phytochromes, especially phytochrome B, was responsible.

However, just like how we all learn to not touch the hot stove after our first burn, researchers also found that the ROS wave triggered a systemic stress memory mechanism. That meant the plant became familiar with the stress and its response was stronger.

“Evolution has realized that these high light intensities don’t just show up and instantaneously leave, but that they might stay around for a while,” Liscum said. “Evolution is adapted to have some system for the chemistry in the plant to change for some period of time before it goes back to what it was before it saw the stress.”

While the paper revealed much about phytochrome B and the systemic response to light stress, the Mittler and Liscum labs want to further investigate the memory and mechanistic aspects of the process.

“The next stage is to figure out how the sensing of the light stress by the receptors and not by the chloroplast triggers this response,” Mittler said.

#IAmScience Mona Kacher

October 30, 2020 By Lauren Hines in #IAmScience Tags: spinal muscular atrophy

By Lauren Hines | Bond LSC

Years ago, when career technician Mona Kacher was still in school, her science teacher asked their students who wanted to dissect a salamander first. Some students were hesitant, others excited, but no one more excited than Kacher who had already raised her hand.

Originally, Kacher was a medical technician in an Army hospital lab. However, when she left the Army, she was encouraged by her then father-in-law to apply for a senior research position at Dalton Cardiovascular Research Center. There, the lab manager asked if she knew anything about the chemistry analyzer they had just bought.

She knew it inside and out.

“So, that started an unintentional career in research, and I’ve stayed with it ever since,” Kacher said.

In her 31 years at Mizzou, Kacher has been bouncing around campus as a senior technician and research specialist working in various labs and disciplines.

“As you know, PIs sometimes lose their funding or funding comes and goes,” Kacher said. “So, I’ve had to piece together a career on campus, moving around a little bit.”

Kacher has worked in oncology, veterinary pathobiology, diabetes, hypertension, Lyme disease, HIV-AIDS and malaria research. She has been listed as a co-author of 20 scientific manuscripts that also include her data.

“Mona’s wide variety of disciplines that she has been exposed to throughout her career absolutely helps strengthen the Lorson lab,” said Chris Lorson, principal investigator at Bond Life Sciences Center. “She is able to draw on techniques she has performed in the past and apply them to various research needs.”

Kacher has been at the Chris Lorson lab at BLSC for the past two years. She’s the only technician there, so she assists others and helps teach methods and procedures to graduate and undergraduate students. Kacher also maintains five mice colonies for Lorson’s gene therapy work regarding Spinal Muscle Atrophy (SMA).

SMA is a genetic disorder that occurs in children missing the survival motor neuron-one gene. The disorder is the leading genetic cause of infantile death worldwide and causes muscle weakness, respiratory failure and premature death.

“SMA has likely affected members of my own family,” Kacher said. “It’s a very sad situation for a lot of families, and working in research that may directly improve the outcomes of the lives for some of these little sick children is very rewarding.”

Kacher is currently working on projects that test treatment methods for SMA and other neurodegenerative diseases. In these projects, infant mice the size of gummy bears receive a spinal injection with the treatment. Spinal injections are also involved in some projects.

“She is focused and hard-working,” Lorson said. “She understands the need for flexibility in the world of research and will persevere until the task is completed. She has a wonderfully positive attitude and a genuine concern for the well-being of those around her.”

Similar to how her research reaches a range of disciplines, her interests are just as varied.

Kacher and her wife started a business named, Shivers Shaved Ice and Shivers Coffee & Donuts in 2017. They owned it for several years until Kacher went back to MU.

In addition, Kacher likes to make jewelry and art. She also plays guitar and used to sing at weddings and in the Columbia Chorale. She still sings with MU’s Choral Union.

All of this creativity seeps into BLSC where she has colorful toys on her desk and a rainbow of organizers on lab shelves.

“Gosh, well, I think I’ve certainly brightened up the lab,” Kacher said.

With so many positions across campus, Kacher believes this one will be her last. She plans on retiring in a few years.

“I enjoy a lot of variety in life,” Kacher said. “So, being able to contribute data and small pieces of information in this field or that field, knowing that all the little pieces together are what makes a cure or moves scientists into the next direction for studying that disease or that condition is very rewarding.”

Learning From History

October 26, 2020 By Lauren Hines in Research Tags: extracellular ATP, plant signaling pathways

Sung-Hwan Cho, a research scientist in the Gary Stacey lab, checks in on the arabidopsis plants that he uses in his purinergic signaling experiments. | photo by Lauren Hines, Bond LSC.

By Lauren Hines | Bond LSC

Until the 1990s, the presence and significance of extracellular ATP, a nucleotide that normally provides energy to a cell, in animal cells was highly contested for decades. Now, the Gary Stacey lab at Bond Life Sciences Center is using that history lesson to explore ATP’s role in plant cells.

Let’s say you have $100 in your pocket. As you’re walking down the street, you throw dollar bills over your shoulder. Sounds ridiculous, right?

Much like these dollar bills, ATP is the currency of cells. When the idea of animal cells dispensing ATP outside the cell to trigger danger signals came out in the 1970s, the scientific community thought it was wasteful and therefore the idea was ridiculed.

“The idea of throwing money over your shoulder is a very good analogy because that’s a good way to influence people,” said Stacey, a principal investigator at Bond LSC. “Give them a financial incentive. It’s the same thing with ATP. The idea is that this is the currency of the cell, but they’re putting it outside the cell in order to signal and influence interactions with their environment or other cells.”

This process of ATP receptors on the cellular membrane bonding with molecules to send signals and communicate between cells is called purinergic signaling.

The term was coined by retired neurobiologist Geoffrey Burnstock in the 1970s when he discovered it in animals; however, Burnstock’s findings were met with skepticism. It wasn’t until 20 years later when the first ATP receptor in animal cells was discovered that his idea gained acceptance.

Today, animal cell purinergic signaling has been used to make drugs that target diseases and develop drug therapies. As for purinergic signaling in plant cells, the research is just beginning. Much like what Burnstock faced, this new research is met with skepticism.

“It was clear to me that if we really wanted to establish this so that people would believe it, we had to get the receptor,” Stacey said.

In 2014, the Stacey lab reported its first ATP receptor called P2K1. Earlier this year, they found another one called P2K2.

“I think more and more people are working on purinergic signaling in plants,” Stacey said. “I think we will see a big explosion of people working in this area. Just as is the case with the animal field, the plant field is really going to take off now that we actually know what the receptors are.”

Currently, the Stacey lab is trying to understand how these receptors work. Research scientist Sung-Hwan Cho from the Stacey lab took over the project regarding P2K1.

“The ATP study in animals is just half a piece of the puzzle,” Cho said. “You need to find the other half of the piece. For 40 years, many labs have already studied this, but in plants, there’s just been a few.”

Research done by the Stacey lab has shown that although not much is known about purinergic signaling in plants compared to in animals, purinergic signaling can impact plant growth, development, defense against diseases and stress tolerance. Cho is currently studying how P2K1 impacts certain metabolic pathways in plants.

In another experiment done by the lab, they found that mutants without the ATP receptor that experienced stress did not grow smaller while plants that did have the receptor and experienced stress grew smaller.

“That says the purinergic signaling is what’s mediating the stress response,” Stacey said. “That is affecting the development of the plant in response to stress… So, if we understand this better then maybe we can make plants that are more drought and stress-tolerant and grow better.”

Four months in, Baker lab hits the ground running and won’t be stopping anytime soon

October 19, 2020 By Lauren Hines in Research Tags: cancer, cell sheets, copper

Post doctorate Harim Tavares from the Baker lab works in “the hood,” which is a space used to prevent researchers and other outside factors from contaminating cells.

By Lauren Hines | Bond LSC

Saliva is often something people take for granted.

It helps break down food, maintain teeth and keep the oral cavity feeling comfortable. But head and neck cancer patients lose those benefits when chemotherapy treatments damage their salivary glands.

Olga Baker set out to research tissue regeneration for these cancer patients by collaborating with the Michael Petris and Gary Weisman labs after setting up shop four months ago as a new principal investigator at Bond Life Sciences Center.

Together, the Petris and Baker labs are looking at the role of copper in salivary gland damage.

“Nobody has asked what happens to copper metabolism during and after head and neck radiation,” Baker said. “Is copper related to the fibrosis that is developing in those patients, so they don’t make saliva? We don’t know. So, we are answering different questions…. We don’t have any data yet, but what we have is immunofluorescence studies showing that those copper transporters are present in salivary glands from mice and humans.”

If the two labs can learn how copper connects to salivary gland tissue regeneration, Baker can get a step closer to helping patients.

The Baker and Petris labs just published a paper with help from the Proteomics Center and the MU Molecular Interactions Core in the journal of Dental Research. Post doctorate Harim Tavares from the Baker lab is the leading author.

The study used synthetic networks of crosslinked polymer chains that can take in large amounts of water called, smart hydrogels. The smart hydrogels were used in the same mouse model as the cell sheets and promoted tissue regeneration on mouse salivary glands. The paper explored how different materials like smart hydrogels can improve tissue regeneration.

Baker’s other focus takes on cancer and tissue regeneration from a different angle in her collaboration with the Weisman lab.

“Dr. Weisman’s group has studied the mechanisms of salivary gland dysfunction for over 30 years, so between these two groups the tools are in place to provide a translational approach to understand and treat salivary gland disorders,” said Jean Camden, a senior research associate in the Weisman lab.

The two labs just submitted a paper on mouse submandibular glands and cell sheets, which are plastic-like sheets where cells grow and detach once it reaches a certain temperature. Kihoon Nam from the Baker lab is the corresponding author. The study transplanted submandibular gland cell sheets into a wounded mouse to see if cells could be transferred.

“We believe that is a good proof of concept for future use in radiation studies,” Baker said.

The Baker lab uses cell sheets with the Weisman lab to study the role of the P2Y2 receptor in salivary gland regeneration. P2Y2 is a plasma membrane receptor that binds the molecules outside of cells and serves as signals to trigger an action.

The Weisman lab previously showed that P2Y2 receptor activation encourages salivary gland cells to migrate together and form a unit capable of secreting saliva.

“At this time, we don’t know what the role of P2Y2R is in the cell sheets,” Camden said. “That is an aim we proposed in a recent TRIUMPH proposal.”

The TRIUMPH initiative — The Translational Research Informing Useful and Meaningful Precision Health initiative — is a pilot grant funding opportunity through the Missouri School of Medicine.

As if two collaborations weren’t enough, Baker is also working on saliva substitutes. The lab just submitted a grant to fund the project.

“If we get the money, we will be able to make a far better saliva substitute as compared to the Biotine, or Aquoral, or Oasis,” Baker said. “Those are the three leading brands. So, hopefully, we can make something better here at MU and commercialize the product.”

#IAmScience Alana Rodney

October 16, 2020 By Lauren Hines in #IAmScience Tags: animal science, cancer, MARC/IMSD

By Lauren Hines | Bond LSC

Research assistant Alana Rodney walked into her high school science class a few years ago expecting to fill another credit. However, it was there that she found her love of genetics.

“I just remember doing the lab and I learned how to use a pipette,” Rodney said. “I was like, ‘Oh, my goodness. This is so cool.’”

Fast forward to now and Rodney just completed her undergraduate degree in May 2019. And she’s not stopping there as she now pursues a master’s in animal science, genetics and genomics to create better treatments for common diseases and cancers.

“I want to eventually study cancers in humans and disease treatments for different types of cancers and other diseases that affect people in general, but especially the Black community because that’s really important to me,” Rodney said.

Rodney plans on eventually applying what she learns from the genome of cats to humans, especially cancer research.

“Cancer definitely has had a big effect on my family,” Rodney said. “A lot of people in my family have breast cancer and other types of diseases. I do think some of that is due to the environment that my family was in. I know that has a direct effect on the genetics of a person. So, some of this hits close to home for me.”

Rodney entered the world of research as an undergrad through the Initiative for Maximizing Student Diversity (IMSD) program. It is now called the Maximizing Access to Research Careers (MARC) program.

“The IMSD/MARC program is also one of the main reasons that I am in science right now,” Rodney said.

IMSD/MARC helps develop the research and professional skills of students from underrepresented groups by paying students to work in labs and exposing them to research.

“The IMSD/MARC program gave me a real sense of community in science,” Rodney said. “I was with a bunch of other students who have similar debt and probably wouldn’t be in grad school if it wasn’t for that program. It really gave me the motivation and push I needed to keep going even when school got hard. Having a community to really say, ‘Okay, let’s study. Okay, let’s talk about it.’”

For the past year, Rodney has been in the Wes Warren lab at the Bond Life Sciences Center working on bioinformatics and experiments for her thesis project.

“She’s been a joy to work with, and she’s very hungry to learn,” said Warren, a primary investigator at Bond LSC. “That’s what I really value in anybody that I work with.”

Rodney recently submitted her first paper to the journal Scientific Reports where she was the first author. The paper explored the effectiveness of whole-exome sequencing, (WES) which is a cost-effective strategy that sequences coding regions in DNA.

WES is usually used on human diseases that express multiple observable characteristics called, phenotypes. This makes it hard to classify which disease it is. WES also helps to identify alleles in genes that cause certain diseases.

In this instance, WES was applied to the DNA of diseased cats and was compared to the DNA of healthy cats as a baseline. WES discovered new variants — differences from the norm — for certain kidney disease in cats.

“That puts it out into the literature so that veterinarians and scientists that are interested in investigating that particular disease now have a candidate they can pursue,” Warren said.

The new variants were labeled as potential causative alleles of the kidney disease in cats.

“That was a nice paper to show that whole-exome sequencing in cats is possible, and that is a viable way to get data on the disease from the cats versus whole-genome sequencing. So basically, the paper just showed the effectiveness of whole-exome sequencing.”

Other strategies like whole genome sequencing cost more and provide slower results, so demonstrating WES as an effective option for research can help further the field.

In addition to her experiments, Rodney loves introducing children to the world of science.

“I’m really passionate about outreach and working with the youth and supporting them,” Rodney said. “I like to do science outreach, so I’ll go to elementary schools and talk with kids in the neighborhood, and if they want to do a science experiment, I’ll do it with them.”

Maybe in one of those science classrooms, Rodney can inspire a new student to pursue a field they love, just like her.

Plant vs. Pathogen

October 7, 2020 By Lauren Hines in Research Tags: plant immune system

Research scientist Jianbin Su studies the immune system in lettuce on the third floor of the Bond Life Science Center.

By Lauren Hines | Bond LSC

Scientist Jianbin Su’s research lately took him outside to look at patches of grass and cracks in sidewalks around Mizzou’s campus, searching for a subject in the wild. He found his subject in the form of wild lettuce.

That search can potentially help Su — a research scientist in the Walter Gassmann lab at Bond Life Sciences Center — better understand the immune system of lettuce and therefore protect it against diseases like Downy Mildew and Xanthomonas, which would increase lettuce crop yield.

Su’s paper under review about how the pathogen effector protein, AvrRps4, interacts with lettuce’s immune system will hopefully soon be accepted in the journal Molecular Plant-Microbe Interactions.

“Scientists in Florida are still focusing on lettuce resistance to Xanthomonas,” Su said. “If we can find a mechanism where lettuce recognizes our protein, this finding can be applied to make lettuce immune to Xanthomonas.”

Xanthomonas causes bacterial leaf spots and is a serious seed-borne disease that results in significant losses for the lettuce industry

To infect a plant successfully, the bacterium must inject 30 to 40 protein effectors, like AvrRps4, in the cell and interact with multiple plant cell functions at once to overcome the host. Effectors for a pathogen can bind to proteins that affect the biological activities of the plant, letting the disease invade the plant, suppress its immune system and allow Xanthomonas to survive.

However, when the plant cell’s receptors recognize the pathogen, it can trigger its immune response. To stop the pathogen from growing, the plant cell initiates a hypersensitive response by killing itself. If the plant can’t stop the pathogen, it will multiply and affect much larger areas of the leaf. This will ultimately destroy the plant tissue and cause the characteristic round, brown dead spots on the lettuce leaves.

“Plants can afford the hypersensitive response because their developmental program isn’t set in stone like in most animals,” said Walter Gassmann, interim director for Bond Life Sciences Center. “They can adjust their growth in real-time…so losing a leaf is not a big deal to a plant, not like us, losing a limb or something like that.”

Wild Lettuce Found on Campus — While studying lettuce immunity, research scientist Jianbin Su took photos of wild lettuce growing on campus. | photo contributed by Jianbin Su.

Once AvRrps4 enters the plant cell, it splits up into two parts: AvRrps4-C and AvRrps4-N. Some plants like flowers, tomatoes and melons only recognize the C part, but lettuce only recognizes the N part of the effector.

“The C part of AvrRps4 has been studied by many labs, and they’ve already found some mechanisms,” Su said. “The C part attacks a group of important proteins that are required for plant immunity. That’s the function of the C part, but the function of the N part is not clear. That’s what I’m focusing on in lettuce.”

Recognition is important because, without it, plant cells can’t respond to fight off the pathogen.

Su is studying lettuce not only because it hasn’t been studied as much, but so far, it’s the only plant that requires recognition of both parts to initiate immunity.

This means lettuce evolved to recognize and attack AvRrps4-C. In turn, the effector evolved by adding a second part to prevent recognition by plants.

This evolutionary choice, if you will, is odd. Instead of getting around the immune response by getting rid of the protein that is recognized, the protein added a second part to itself. This means AvRrps4-N, the original part, must possess a vital function for the pathogen worth keeping.

“That’s why we think this effector arose in nature,” Gassmann said. “It’s because the first part triggered a very strong immune response, something else got tacked on to it to weaken that immune response to give the pathogen a leg up.”

This evolutionary battle can be seen in Mizzou’s very own backyard. Su found five different types of wild lettuce. After testing if the types were able to recognize the N part of the effector, he found two of the five did.

Since some did and others did not, Su thinks the receptor for recognizing the effector has been lost in some wild lettuce types due to evolution and the absence of the pathogen in certain areas.

“We haven’t found the lettuce receptor but based on this information we can narrow it down,” Su said. “Right now, we have 36 candidates. We are already sure that among the 36, there’s 99.999% that there is one receptor that recognizes our protein.”

Su still has much work left to do but, for now, he resubmitted his paper Oct. 5.

“Once we identify the receptors that recognize our protein, our research will go into the next direction, and maybe have some application purpose for our research,” Su said.

Beyond the Vaccine

September 25, 2020 By Lauren Hines in Research Tags: COVID-19, virology

Lucas Woods from the Weisman lab watches lung cancer cells and oral epithelial cells grow. | photo by Lauren Hines, Bond LSC

By Lauren Hines | Bond LSC

Vaccine development remains a central goal to get the current COVID-19 pandemic under control. While vaccines are highly vital in the fight against the current pandemic, what if scientists could prevent the virus from entering cells altogether? Researchers at Bond Life Sciences Center are working to do just that and, so far, they’re the only ones at Mizzou on the case.

For the Gary Weisman lab, that starts with their study of a family of purinergic receptors which are found on the plasma membrane of cells. Molecules outside the cell bind to receptors and serve as signals to trigger an action, whether it’s transporting something into a cell, alerting its defenses or initiating programmed cell death. The specific receptors they study sound off one of the first alarms to alert host immune cells when a cell is damaged.

Weisman, Bond LSC principal investigator and Curators’ Distinguished Professor of biochemistry, noticed that the spike protein in the virus that causes COVID-19, SARS-CoV-2, shares an amino acid sequence — arginylglycylaspartic acid or RGD — with one of the receptors his lab studies named, P2Y2.

“So, we had this one niche that no one I think has followed,” Weisman said. “Even though people understand RGD sequences are important for protein to protein interactions, and possibly viral entry, no one has looked at this with respect to coronaviruses.”

While ACE2, a plasma membrane receptor, serves as the primary cell-surface receptor for SARS-CoV-2 binding, a potential role for the RGD sequence in the spike protein is to bind to alternate receptors and subsequently enhance viral infectivity.

“We postulated that if there was a way to use our receptor, it might be to block the entry of the virus,” Weisman said. “The virus can’t replicate on its own. It has to get inside the cell to be replicated, so if we prevent the entry, we can potentially stop the infections.”

They found plasma membrane receptors like ACE2 and P2Y2 all share this sequence that binds to other cell-surface receptors called, integrins. The lab is currently exploring ways to block these pathways without blocking other functions.

Few other labs have made this connection because RGD is not known to be present on many of the membrane receptors. In addition, the Weisman lab already has the supplies and connections to study these receptors.

“We, as the lab, have been studying this receptor and this family of receptors for so long that if there is a lab that has the tools and the knowledge to answer this question, I definitely think that is us,” said Kevin Muñoz Forti, Ph.D. candidate for the department of biochemistry.

Kevin Muñoz Forti is doing cell culture work in “the hood,” which is a space used to prevent researchers and other outside factors from contaminating the cells. | photo by Lauren Hines, Bond LSC

The lab partners with Kamal Singh, assistant director of the Molecular Interactions Core at Mizzou and associate research professor in the department of veterinary pathobiology, who works with viruses in a way that won’t infect workers.

Singh achieves this by using look-alikes, or pseudovrises, of the spike protein on SARS-CoV-2. To the cell, this mimics the outer shell of SARS-CoV-2, but is not contagious.

Even though the Centers for Disease Control and Prevention and Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, expect a vaccine soon, this work is for the long run.

“I can guarantee you this isn’t the last coronavirus that will come up,” Singh said. “There will be many because it has been kind of periodic lately. Coronaviruses have been emerging, so the research done in collaboration with Gary’s lab will definitely be available for… future coronaviruses.”

Coronaviruses are a family of viruses which may cause respiratory illness in humans. The most recent diseases, before COVID-19, caused by previous coronaviruses were Severe Acute Respiratory Syndrome (SARS) from 2002 and Middle East Respiratory Syndrome (MERS) from 2012. Severe Acute Respiratory Syndrome Coronavirus 2 is the virus that causes COVID-19.

“This is the virus that causes COVID-19 or SARS-CoV2,” said Lucas Woods, Weisman research lab manager. “If this type of research were to have been investigated during the first coronavirus epidemic, there might have been some type of lead on the type of work we’re doing… so, absolutely this work will be useful after a vaccine or treatment is available.”

Looking ahead, the study has two years of funding from the American Lung Association in addition to grants from the National Institutes of Health. The Weisman lab hopes to eventually make it to clinical trials, but the road from basic research to clinical trials is long and arduous.

“What’s on our side, at least for the future, is that with some of these pathways we’re looking at, there are already available drugs that target these particular pathways,” Woods said.

These pathway-blocking drugs aren’t approved for humans yet, but this research could facilitate clinical scientists to test the safety of these or related drugs in humans.

The Weisman lab’s research of P2 receptors can be applied to many systems in the body and other diseases. This also allows for more ways to receive grants to fund studies longer. Along with the COVID-19 studies, they study P2 receptors in diseases that affect salivary glands.

Cheikh Seye, Mizzou professor of biochemistry, studies vascular diseases that relate to the receptors studied by the Weisman lab. Seye understands that one of the complications of COVID-19 in humans is vascular related.

“I mean there’s a lot of interaction between the vasculature and other systems, so it doesn’t stay with the salivary gland,” Seye said. “It’s all interconnected, so that’s why we need to have a multi-dimensional approach.”

In addition, the lab has found commonalities between oral and lung epithelial tissue that may contribute to COVID-19.

While this study has quite a bit of potential, it’s a long way away from seeing practical results.

“All the people in the lab have confidence because they have been successful on their own doing this before,” Weisman said. “So, it’s just another challenge, but we know how to get the answers, we have the tools and we’re optimistic that we’ll find out something.”

Researchers working on this study include Gary Weisman, Kamal Singh, Lucas Woods, Cheikh Seye, Jean Camden and Kevin Muñoz Forti.

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