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Madison Ortega #IAmScience

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Madison Ortega, a junior biology major, works in the Rosenfeld lab at Bond LSC. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because research gives me an avenue to explore my curiosity and possibly discover something groundbreaking.”

Research is all about discovering the answers to the unknown, pushing boundaries and exploring the depths of the field. As a junior biology major, Madison Ortega is already getting a taste of that.

Her freshman year, Ortega got a brochure for the Initiative for Maximizing Student Diversity program (IMSD). This program encourages students to get involved with science even if they have had little exposure to it previously. Its ultimate goal is to provide a foundation of advanced science skills for minorities that can be applied to higher degrees within the field.

“I got to start exploring research right away through IMSD,” Ortega said. “It gave me the opportunity to look into various labs.”

Ortega landed on working in Cheryl Rosenfeld’s lab at Bond LSC because she felt she would have ample opportunities. That experience has led her to an individual project working on samples of spiny rats — an endangered species from Japan.

“The male doesn’t have a Y chromosome, so we’re trying to figure out how sexual differentiation occurs in the species without it,” Ortega said.

Through Bond LSC, she connected with Hokkaido University in Japan who donated the samples.

“They’re not fresh samples — they’re about 10 years old,” Ortega said. “But I showed interest in the project and ended up getting to work on it one-on-one with our lab mentor.”

In addition to her individual project, Ortega works with other undergraduates within her lab.

“We’re doing a variety of experiments that include social testing on mice,” Ortega said. “We do anxiety testing and also perform Barnes maze with the animals.”

These mazes and tests aim to see the impact of chemicals in the environment that mimic hormones like estrogen and impact animal growth and development.

“Basically, we’re trying to see how endocrine disruptors we feed the mice affect their offspring,” Ortega said. “We want to know how it affects them neurologically. In order to accomplish this, we are collaborating with various other groups in Bond LSC.”

Ultimately, they’re aiming to uncover if Bisphenol S (BPS) has any impact on the mice neurologically. These substances are similar to Bisphenol A (BPA), a chemical used as a hardener in production of plastics and in other manufacturing. As concern has raised over BPA, companies have replaced the chemical with BPS and others to allay public anxiety over its impact. But not much research has been done on BPS and its effect on animals.

“They may be found to have some neurological effects, so research is trying to uncover what exactly those are,” Ortega said. “The many tests we run will help us understand to the extent these chemicals are affecting us.”

After graduation, Ortega envisions herself continuing with research as a focal point of her career.

“I love research,” Ortega said. “My end goal is medical school, but I’m considering a program that combines a master’s degree with a Ph.D. in either dermatology or pediatrics.”

Regardless of her path, the lab work she does now leaves her prepared for the future.

“I spend a lot of time in the lab with my team and individually,” Ortega said. “It’s fun to have ownership of a project, and it’s also fun to work with other undergraduates and have camaraderie. I’m really fortunate.”

The business of proteins

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Proteomics Center associate director Brian Mooney holds up a sample before using a machine to collect data on its proteins. | Photo by Samantha Kummerer, Bond LSC

By: Samantha Kummerer, Bond LSC

The Proteomics Center runs on proteins.

This research core facility is like a small business and is situated in the Bond Life Sciences Center. It has helped improve agriculture, opened doors for new medical applications and lead to greater insight into human diseases.

Proteins are some of the most plentiful and common building blocks of all living organisms, making structures in cells but also are key to antibody defense, enzymes to carry out chemical reactions and as messengers to coordinate biological processes.

This complexity makes an essential building block far from simple.

Figuring out what proteins exist and how they function is key to many experiments and that’s where Mizzou’s Charles W. Gehrke Proteomics Center comes in.

The Center looks at thousands of proteins with their current technology consisting of six mass spectrometers worth more than $2 million. They serve clients across the UM System and as far away as Mexico and Canada.

At its core is Brian Mooney, associate director of the center and Roy Lowery, an expert in protein isolation and fractionation and is also learning mass spectrometry.

The Center is often juggling multiple clients each week and sometimes each day. For each new project Mooney sits down with researchers, helps them develop an experimental design, and takes their samples to generate data.

“Sometimes you get to that Eureka moment and you say, ‘I thought this was happening but my hypothesis was wrong and actually this is happening’ and leads to new directions in research. That’s what we’re here to do,” Mooney said.

The center is able to run experiments that look at proteins from a global scale and experiments that target just a small number.

For studies that want to find the difference between a normal cell and a mutant, a global analysis is used to look at all the proteins.

Mooney breaks a cell down and removes everything but its proteins. This fractionation allows researchers to examine a lot more proteins more closely.

“Typically the things that are doing the control in the cell are maybe not as abundant, so you need to dig deeper, so that’s the point of the fractionation,” Mooney explained.

To look even deeper into these, the center can use a technique called SDS-Page to sort the proteins by size.

“We’ve done everything from full plants so leaves and roots, we’ve done it for bacteria cells, we’ve done it for blood, both in humans and in animal models and then we have also done some specific tissues whether it be heart or kidney,” Mooney said explaining the range of this technique.

Recently, the center helped with a project aimed at making better corn hybrids for farmers by finding out which proteins played a role in a process called heterosis.

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Brian Mooney looks on to data collected on proteins in the MU Proteomics Center.| By Samantha Kummerer, Bond LSC

“We were able to see specific proteins that were involved in processes that suggest this is why you get a taller and healthier hybrid plant,” Mooney said. “One of the major findings was elevated stress-responsive proteins conferring an ability to withstand stress.”

The center also helped researchers at the Truman Memorial Veterans’ Hospital compare heart tissue between healthy and diseased hearts.

With a targeted approach, the clients already know what proteins they are interested in, so Mooney is able to use equipment to zero in on a much smaller number.

“We are working in a group in biological sciences that are looking at nerve tissue and in this case they are just interested in five proteins and what we’re able to do is ignore everything else and get really good numbers in how much of these five proteins are there,” Mooney explained.

The center is also there to educate. Mooney explained often clients don’t have a clear understanding of proteomics.

This mission of education also occurs for students. Graduate students and post-doctoral students are trained on how to work the instruments and to analyze the results. On the undergraduate level, Mooney presents hands-on lectures and labs to biochemistry classes. The Center also participates in a unique MU-Industry undergraduate internship program (Biochemistry Dept. and EAG, Columbia).

Sometimes the exposure of what the center’s capabilities sparks cross-discipline projects.

In 2015, Mooney worked on a collaborative project with the MU Medical School studying cataract formation in humans.

Last year, Mooney teamed up with biochemists and mechanical and aerospace engineers.

Mooney explained that before the involvement of the Proteomics Center, the researchers were firing a laser at a piece of a protein called a peptide.

“They saw that something weird happened and wanted to know what that weirdness was on the molecular level, so they came here,” Mooney said.

This collaboration led to a publication on how targeting proteins and peptides with a laser can control biological processes in cells and tissues.

MU is not the only university with a Proteomics Center, but having it local comes with a number of advantages. Mooney said subsidies from MU allow the center to offer reduced rates to MU clients. Another advantage is the ability to consistently have someone nearby to talk through their experiment with.

Since 2002, the center has grown from a handful of customers to more than 50 customers a year and a total budget of about $250,000. Direct income from research usually covers about 60-70% of that total, with the remainder being covered by the Office of Research.

Mooney said part of this success and growth is due to an increase interest in proteomics from scientists.

While genes allow researchers to know what might be in the cell and mRNA tells them what is going to be in the cell, the proteins reveal what is currently in the cell.

Many researchers have focused on cells at the DNA and mRNA level, but are now discovering it’s important to consider the protein as well.

Soon a new instrument will be added with funds received through a National Science Foundation MRI grant, one of two awarded to MU in the last 10 years. With the upgraded mass spectrometer, Mooney said, data will be able to be collected faster and better. This advancement will continue to allow the center to do what it does best – proteins.

The MU Proteomics Center is named for Charles W. Gehrke, a former MU professor of Biochemistry. It is one of 10 research core facilities subsidized by MU’s Office of Research to provide services to a range of scientists and researchers across the UM System and the world.

Janlo Robil #IAmScience

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Janlo Robil, a Ph.D. candidate in Plant Developmental Genetics, admires one of his plants. Robil works in the McSteen lab in Bond LSC. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because adding a small puzzle piece to the bigger picture is my source of joy.”

Janlo Robil found himself with a difficult decision when he entered a master’s program at Ateneo de Manila University in the Philippines.

His passion for insects made him want to pursue entomology, but the lack of coursework in the area made him consider other options. Not wanting to put off his studies for another year, Robil took a course called Plant Microtechnique. After that, he was hooked, a weird place to be for someone with no prior interest in plants.

“I found myself amazed by the diversity and intricacy of plant cells and tissues,” Robil said. “And studying these structures in the laboratory was even more interesting.”

From there, his passion only grew. It led him to apply for and be accepted as a Fulbright Scholar — a prestigious exchange program that allows recent graduates to pursue further education in over 140 countries. He chose to attend Mizzou over Iowa and North Carolina because of its strength in plant sciences.

Now, a year and half into a five-year Ph.D. program in plant developmental genetics, Robil works in Paula McSteen’s lab at Bond LSC.

“I was drawn to her research because it encompasses the areas of biology that I am truly fascinated by: plant morpho-anatomy, developmental biology and genetics,” Robil said. “For me, working in the McSteen lab is a unique opportunity to explore fundamental biological questions using an excellent model system, maize.”

Robil studies corn as a key component of his dissertation.

“The overarching theme of my dissertation is the role of plant hormone auxin in vein development and patterning in maize leaf,” Robil said. “I am interested on how the dynamics of auxin shape the formation and density of veins during different steps of leaf development.”

He chose this topic because of how influential it is to a variety of areas of science.

“This research is important to both fields of developmental biology and physiology because optimized density and spacing of leaf veins in C4 crops like maize is a key requirement for their efficient metabolism and productivity even in arid conditions.”

Robil is also able to better his home country while studying at Mizzou.

“Because Philippines is a developing country, conducting basic research is a luxury and we try to focus most of our resources to applied research.” Robil said. “The United States houses the opportunity to explore the basic side of research, which provides the foundation for applied research in the future.”

At Bond LSC, Robil has been able to take his research to the next level.

“I value the collaborative and interdisciplinary atmosphere here,” Robil said. “You can find experts from a variety of disciplines that you can consult or work with to find answers to your research problems.”

Those insights have helped Robil grow as a researcher and work toward his dream of helping alleviate world hunger. While that’s no small task, he tries to take it one day at a time.

“Never lose the wonder of discovery,” Robil said. “It may not always be that novel or significant, but discovering new things should be considered a personal success.”

Bond Life Science Investigator honored with two distinctions

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Chris Pires in his greenhouse in the Bond Life Sciences Center.

By: Samantha Kummerer, Bond LSC

“If you told me when I was an undergrad at Berkley or when I was working at a consulting firm in San Francisco when I was 22 that I would be a professor in Missouri working on broccoli, I would have laughed my ass off,” Bond Life Sciences investigator Chris Pires admitted.

But that work on broccoli has taken him far.

Pires recently received the 2017 Chancellor’s Award for Outstanding Faculty Research and Creative Activity in Biological Sciences.

Pires was also elected as a Fellow of the American Association for the Advancement of Science. The honor places Pires alongside other AAAS fellows including Thomas Edison and Margaret Mead as well as some of the most productive faculty members at MU.

The awards add to a long list of honors received over the years ranging from Thomas Reuters’ Highly Cited Researcher to MU Outstanding Research Mentor.

Despite being no stranger to awards, his impact still surprises him.

“For me what’s nice is people who I’ve had some impact on in the past say things,” he said smiling.

Both recent distinctions cite his contributions to plant evolution and sequencing of genomes and their impact towards improving crops and understanding biodiversity.

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Chris Pires, a Bond Life Sciences Center researcher, accepts an award from MU Chancellor Alexander Cartwright. Pires won the 2017 Chancellor’s Award for Outstanding Faculty Research and Creative Activity in Biological Sciences. | Photo by Kate Anderson.

While his work on polyploidy and hybridization on plants is internationally renowned and even earned a shout out on the television show “The Big Bang Theory”, the findings go right over the average person’s head.

So, instead, he compares his research to dogs.

Golden Retrievers and Chihuahuas don’t look alike but both are dogs. This is the same for broccoli, kale and cabbage — they are all are apart of the same genus of plants, Brassica.

Pires said he started using that analogy after years of getting the conversation wrong.

One of Pire’s passions is communicating the research he does, including clearing up misconceptions surrounding scientists and professors.

Some days he compares his lab and 80-hour workweek to the life of a small business owner running a multi-million dollar business. Other days it’s a football coach.

“I do all those things, you just don’t know it. I train people, I hire people, I fire people, I do communication, I spend a lot of times applying for grants, I give talks,” he said comparing duties of a coach to his everyday life.

He is also a talent scout.

Pires travels the world and visits MU undergraduate research fairs searching for students passionate about making a difference and are able to answer a simple question: Why?

“They just have to have an answer,” he said. “What I don’t want is the students where it’s just the next step in life.”

The passionate and devoted teams he builds pays off.

He has put out more than 140 publications during his career, 11 in 2017.

His success he attributes back to team science.

“I’m being recognized for stuff my lab does and all the people I collaborate with, so I’m happy to be acknowledged for the achievements of our group,” Pires said.

As the researcher looks on to his future at the university he said he hopes to transition from mentoring undergraduates to mentoring faculty and post-doctoral students.

Pires also wants to be a part of helping to foster cross-discipline research teams both inside Bond LSC and across campus.

While it’s not where he expected to he’d be, it’s where he found his passion. Now he is committed to helping his students get their dream job even if it changes along the way.

“A good day is when I go into the lab and I feel like I’m impacting the six or seven people in my lab but when you realize your impact has maybe been bigger than you realize, that’s nice because you just don’t know,” Pires said.

Chris Pires is a Bond Life Sciences’ Investigator and Biological Sciences professor at the University of Missouri. He is also a member of the Interdisciplinary Plant Group and MU Informatics Institute. He received his bachelors in biology at the University of California, Berkeley and his Ph. D. in Botany from the University of Wisconsin.

Madeline McFarland #IAmScience

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Madeline McFarland, a senior biochemistry major, works in the Burke Lab in Bond LSC. | photo by Allison Scott, Bond LSC

Science isn’t limited to the lab. It’s more of a mindset than a discipline, and Madeline McFarland knows this all too well.

As a senior biochemistry major working in Donald Burke’s lab in Bond LSC, McFarland experiments with ribonucleic acid (RNA) to study the origin of life before DNA and protein served as genetic material and catalyst, respectively.

“I’m interested in the RNA World Hypothesis and how RNA may have played a role in getting life started on our planet,” McFarland said.

This hypothesis suggests early forms of life on Earth may have relied solely on RNA to store genetic information and to catalalyze, or spur, chemical reactions. The theory goes that DNA eventually evolved to take its place due to the instability and ineffectiveness of RNA.

In the lab, McFarland focuses on using a program called systematic evolution of ligands by exponential enrichment (SELEX), which filters the RNA so she can find which strands do what she’s looking for. Specifically, she’s trying to determine if the RNA can make a reaction happen. If McFarland can find this connection, scientists would see that as support for for the RNA World Hypothesis.

“I’m trying to see which RNAs can perform a catalytic function,” McFarland said. “By doing that, we can kind of start to think about how RNA used to function in early earth.”

Her typical day starts at 9 a.m. when she heads to Bond LSC to get her experiments set up for the day.

“I go to class while they’re incubating,” McFarland said. “My science allows me to set stuff up and have a break while it’s running. I’m usually running experiments four days a week.”

McFarland was inspired by the work being done in Bond LSC and the analytical way of thinking about experiments.

“[Research] is kind of nailed into you as soon as you step on campus,” McFarland said. “That was the motivating factor, but I came to love it for a lot of reasons. It’s really shaped the way I think about things.”

When she’s not wearing her lab coat and investigating the origins of life, McFarland spends her time working in environmental efforts at Mizzou.

“I’m really passionate about sustainability in all of its forms: environmental, economic and social,” McFarland said. “I lead the electronic waste drives around campus, and I’m co-directing sustainability week this year.”

McFarland is also a co-president of the biochemistry club.

“In our meetings, we bring in grad students and faculty to talk about career options, so everyone can ask questions,” McFarland said. “We also do fun events. Last night, we had a biochemistry-themed breakout room. They had to balance chemical equations and transcribe and translate a DNA sequence to spell out a word. We have a lot of fun with it.”

All of her work in the lab in combination with her research at Bond LSC has only strengthened her bid for her next endeavor: medical school.

“I’m passionate about communicating science, and I think medicine would allow me to do that,” McFarland said. “I like the idea of radiology because it allows you to look at an image, or data, then think through things on your own, which is a lot like research.”

If she doesn’t end up at medical school, McFarland would like to continue to pursue education. She could see herself attending graduate school.

“I’m interested in a master’s in public health,” McFarland said. “It would allow me to expand my knowledge of science and how it relates to health beyond the scope of the lab.”

Regardless of if she continues to learn through medical or graduate school, though, McFarland credits research for having an immense impact on her career.

“Research has really shaped the way I think about things,” McFarland said.

Inside agriculture’s hottest controversy: dicamba

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A soybean plant grows in the Bond Life Sciences Center’s greenhouse. | Photo by Samantha Kummerer, Bond LSC.

By Samantha Kummerer, Bond Life Sciences Center

Every summer, MU Bond Life scientists Gary and Bing Stacey plant soybeans. In the summer of 2016, they were testing mutant crops’ tolerance to different herbicides. Among the multiple weed killers tested was one called dicamba.

The researchers knew this particular chemical was tricky so they turned to an expert to apply it, MU herbicide researcher Kevin Bradley.

The next morning, a soybean breeder with a neighboring plot discovered his soybeans were damaged.

“These were plots where some of his graduate students experimented so they basically couldn’t use any of their data and we felt terrible, but we explained to them we took every precaution we could possibly take but it was this vaporization that took place,” Gary Stacey explained.

What Gary Stacey didn’t understand at the time was dicamba has an ability to travel even after it is sprayed. The herbicide doesn’t just kill weeds, it kills or damages everything not engineered to be resistant to it.

“So let’s say I spray it in this spot right here. You would think its localized but if the temperature and humidity conditions are right it will vaporize and come up and then go into the air,” Gary Stacey said.

Just how far it can travel and how much damage it can achieve was realized all too well by farmers throughout the country this year.

An estimated 3.5 million acres of soybeans were damaged this summer.

One obvious solution may be to simply stop using the weed killer. But the issue is not that simple.

“This is the hardest issue I can remember because there are good responsible farmers on either side of the issue,” said Missouri Farm Bureau president Blake Hurst.

With so much on the line for all sides, dicamba has tangled farmers, corporations and researchers together in a controversial issue.

Bradley is right in the middle. He’s received calls from farmers who just lost 10 percent of their income for nothing they did wrong.

He’s also received calls from people who are upset by any suggestion that anything about the chemical is wrong. These are the farmers who need dicamba to control weeds that are no longer responding to the traditional weed killer Roundup.

“I’ve had the farmers who planted the traits saying ‘These are my highest yields ever how can you say these things?’ And their neighbor across the road just lost 20 bushels an acre because of your highest yields ever. It’s just a very personal issue for each person involved,” Bradley explained.

One case got so personal that a farmer in Arkansas allegedly shot his neighbor.

“I’ve been here for 14 years and I’ve been doing this kind of work for 20, never seen anything like this is agriculture. Period. Never seen this level of controversy between farmer to farmer and farmer to company or between company and university people. I’ve never seen anything like this,” Bradley said.

Dicamba is not a new formulation, but its use is. Monsanto developed genetically modified soybeans and cotton seeds that are resistant to dicamba. One of the problems farmers are pointing to is that Monsanto released the new seeds while still in the process of developing a better formula of dicamba. The new formula aimed to reduce volatilization, a tendency to vaporize after being sprayed on fields and then drift to neighboring areas. Monsanto claims the new formula reduces volatility by 90 percent, but Bradley said 90 percent is not 100 percent.

Bradley’s work has been consumed by this single herbicide as he tries to find the truth of what aspect of dicamba is causing the damage.

In Bradley’s eyes, there are four factors contributing to the widespread damage: physical drift mistakes (spraying with the wind, nozzle not attached correctly), tank contamination, temperature inversion, and volatility.

These factors are recognized by other researchers and Monsanto. The disagreement is over which factor is most at fault.

“Monsanto has a pretty high number for the farmer fault percentage,” Bradley said explaining the blame game. “ I don’t know when they’ll ever really say, ‘yeah, volatility could be contributing to this problem, too’ and that’s the difference between university weed science.”

This contributes to the confusion among users.

“You don’t know who to believe,” Gary Stacey said.

But Gary Stacey thinks this is where researchers are able to help. By acting as an objective third party, scientists can sort the fact from the fiction.

“We’re just trying to get out the truth and what science says, that’s my job,” Bradley explained. “I don’t care necessarily what amount of money a company has invested in something. Our job is to call it like we see it and show the science.”

With a controversial issue like this, sometimes the truth comes with some risk.

MU has been conducting experiments that test the air for the volatility of the chemical. The research is detecting dicamba in the air up to four days after initial application of the chemical. Bradley explained this is not something the companies want to be made public and there’s been considerable pushback.

In addition to research, Bradley is working with the Missouri Department of Agriculture to create training courses for farmers wanting to use the chemical next season.

Despite millions of damaged acres, dicamba is not going away anytime soon.

Gary and Bing Stacey haven’t used dicamba again, but many farmers making their money off crops have no choice. Bradley said Monsanto is planning on doubling the amount of dicamba-resistant soybeans in 2018 and many of the farmers who have been continuously hit by their neighbors’ chemical plan to plant the new seeds.

Bradley said part of the issue is soybeans are not a crop people directly consume. In general, soybeans yields were considerably high this year, so the damaged acres didn’t make as big of an impact on overall production.

“I think the only thing that is going to make a difference next year is if we have an off-target movement that is hitting more high-value crops, more high-value plant species throughout a wider geography,” Bradley said.

If this same type of damage was affecting produce people directly consume or trees, Bradley thinks dicamba would have been off the market by now.

EPA will reevaluate the use of the herbicide next November. This is one of the first times Bradley can remember that the industry granted only a two-year registration.

“I am absolutely convinced that if we have a summer in 2018 like we had in 2017, it will not be renewed,” Hurst said.

Bradley is not so certain. He said he has heard mixed reviews about how the future of this controversial weed killer could go.

“It is an unique situation for sure, hopefully it ends soon,” Bradley said.

German heart and lung researcher speaks at Bond LSC

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Scientist Thomas Braun speaks at Bond LSC about skeletal muscle regeneration. Braun is the director of the Max-Planck Institute that studies the heart,lungs and blood vessels.| Photo by Samantha Kummerer, Bond LSC

By: Samantha Kummerer, Bond LSC

Thomas Braun, a researcher with the German-based Max Planck Institute for Heart and Lung Research, visited MU for a Bond Life Sciences and Mizzou Advantage seminar.

The Max Planck Institute aims to find treatment for heart and lung disease. Part of its research focuses on stem cells and how they can decrease damage done to patients’ tissues who suffer from heart or lung disease.

Many components can interfere with effective muscle regeneration and a lot of those this components are connected to cell death.

Braun’s talk focused on the epigenetic and transcriptional control involved in skeletal muscle regeneration. His research explores cell death’s effect on muscle regeneration. They initially hypothesized that cell death would interfere with regeneration.

Muscle regeneration requires satellite cells. Satellite cells, aptly named for being located near muscle and nerve cells, help skeletal muscle fibers grow, repair and regenerate.

When cells become obsolete they activate a cell program to commit suicide. This cell death comes in the form of apoptosis — normal programmed cell death triggered to eliminate old, unnecessary or unhealthy cells — and necroptosis that is a death by inflammation to counter viruses and other disease.

Braun said when muscle fibers break down there is lots of killing of cells.

“We wanted to see if we take the muscle stem cells out of the tissue and put them into a dish whether they would still maintain this increased function to undergo program cell death and quite interestingly this enhanced tendency to go into cell death is actually maintained even after a few different transitions in vitro,” Braun said describing a particular experiment.

This increase cell death, Braun hypothesized, is caused by changes in the chromatin, a complex of DNA and protein.

To better understand exactly which cell death program was responsible for this increase, Braun’s team repeated the experiment but block certain components. This led them to discover the increased cell death correlates with an increase in necrosis.

Braun also believes there are some epigenetic mechanisms involved. Epigenetic involves biological mechanisms that switch genes on and off.

CDH4 is a component of a complex within this epigenetic function. The larger complex is a repressor and keeps the chromatin together. The researchers thought CHD4 might be what is acting on the pathways

“This actually goes along with a massive increase in cell death so this lack of proliferation of the fiber is simply dependent or caused by the cell death of these satellite cells. They undergo cell death and therefore cannot proliferate,” Braun explained.

Braun said his team landed on the conclusion that normally CDH4 represses the expression of

RIBK3, a protein-coding gene, and thus prevents necrosis cell death. But without CHH4, necrosis begins, cells die.

There are still many questions and experiments that lie ahead to figure out the details involved.

Braun’s talk was made possible by the support of Mizzou Advantage and Bond LSC.

 

Makenzie Mabry #IAmScience

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Makenzie Mabry, a Ph.D. candidate, works in the Pires Lab in Bond LSC. | photo by Allison Scott, Bond LSC

For Makenzie Mabry, every day is a new puzzle when it comes to science.

That desire to solve new problems led her from wanting to be a veterinarian to considering much less cuddly focus in plants.

“I think the beautiful thing about research is that it evolves itself,” Mabry said.

Although she had an acceptance letter to vet school in tow, she altered her career path to work with a new passion: plants. That led her from California to the lab of Chris Pires at Bond LSC.

“I did all of my undergraduate studies [at San Diego State University] with a vet school plan,” Mabry said. “I took a class my senior year talking about plants — Taxonomy of California Plants — with a great professor [Dr. Michael Simpson], and he really sold me on how unique plants are. They break all the rules.”

With vet school no longer in her plans, Mabry volunteered to work with Dr. Simpson and learn as much about plants as she could.

“I was all ready for vet school and I emailed him a week after I was supposed to start to volunteer,” Mabry said.

After two years of volunteering, Mabry began working toward a master’s degree. During that time, she studied a plant native to her home state of California, Cryptantha. She also studied those which occur in Chile and Argentina by visiting both countries.

“That fueled my passion for research,” Mabry said.

However, it wasn’t until five years ago that Mabry met Chris Pires at a conference in Columbus, Ohio.

“He was very energetic and I had just started learning about polyploidy [which Pires studies]. Three years later, he somehow convinced me to move from California to Missouri,” Mabry said. “I really enjoy the work I’m doing here, and it was a good decision.”

Now as a third year in Pires’ lab at Bond LSC, Mabry uses Brassicales — a family of plants that range from papaya to Brussel sprouts — to explore the multiple genomes of plants. She enjoys her lab work, analyzing data and getting to know the plants.

“Learning the subtle differences between them — whether branches are really close together or their leaves are clustered — is key,” Mabry said. “Being able to account for those differences might mean a lot for being able to find genes that are responsible for them. You have to know what those differences are to know what genes are responsible for it.”

Specifically, Mabry tries to understand how polyploidy — when an organism duplicates their genome to end up with two or more sets of chromosomes — comes about and what impact it has on plant species.

“We want to prove that polyploidy can lead to adaptive variation,” Mabry said. “It can be two different species forming a hybrid, and they keep all of their chromosomes, or a single species that doesn’t go through reduction. That’s the major question our lab is focusing on.”

These extra chromosomes can potentially give a plant new traits that help them react better to the environment or reproduce better without compromising essential plant functions. There are complexities to polyploidy that make deciphering its existence difficult, though. For instance, they’re trying to uncover why certain genes are kept and others aren’t.

“There’s evidence that there’s one genome that’s dominant to the other,” Mabry said. “Polyploids have a larger gene size, so that helps them accommodate.”

And, as a result, Mabry’s research requires coding skills.

“If you want to be successful you need to know how to code. You at least need to know what data is put in and what comes out,” Mabry said. “In the next 10 years, I think it’s going to be even more of a part of the undergraduate curriculum – it’s going to have to be.”

Luckily, Mabry doesn’t work alone.

“I’m really grateful because I have four amazing undergrad students who work with me,” Mabry said. “I could not do it without them. They all have individual projects that they are responsible for and it is very rewarding to watch them succeed in writing grants, presenting their work, and getting results.”

Ultimately, though, the undergraduates she works with are a big reason why she envisions herself in academia.

“Mentoring — that’s what keeps me going every day,” Mabry said.

Celebrating a mystery solved

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Roberts honored for breakthrough discovery in reproductive biology 30 years ago
By Eleanor C. Hasenbeck | Bond Life Sciences Center

In 1987, Michael Roberts published a groundbreaking discovery that changed the world of reproductive biology research.

Roberts and members of his lab discovered that a type of protein, an interferon, impacted how the bodies of animals such as sheep, goats and cows, recognized an embryo early in pregnancy. Previously thought to only be a part of a cell’s immune system response, this new signaling role changed the field.

In honor of his lab’s groundbreaking discovery, Roberts recently curated a section of six reviews examining the history of the discovery and current research that has built on it for the November issue of the journal Reproduction.

The discovery revealed an unknown in the reproductive systems of the ruminant family of animals, including sheep, goats, cows and deer. When an embryo first begins developing, before it’s placenta even attaches to the uterus, it releases interferons. Only present for a few days, these proteins signal to the mother’s body that the embryo is there. It triggers the response that keeps the animal from going into heat, basically shifting the animal’s hormones from breeding mode to pregnancy mode.

If the embryo doesn’t release interferons, the mother miscarries. Placing interferons in sheep that were not pregnant made the animals pseudopregnant, a false pregnancy in which no fetus is present.

Scientists at the time knew something made the mother’s body recognize the embryo, but they were not sure what. The discovery of interferon-tau was a mystery solved. That this ‘something’ was an interferon was also a surprise. Before Roberts and his co-discoverer, Fuller Bazer, found interferon-tau, researchers thought that interferons only function was in the immune system. Other interferons help the body recover from viral infections, like cold and influenza, Roberts said. The discovery that the protein also played a role in pregnancy caused some hubbub. It even caught the attention of The New York Times, Roberts said.

“It opened up a whole new area,” he said. “We all the sudden understood how these animals got pregnant, so people went off in all sorts of directions with it.”

The discovery of interferon-tau created opportunities for more research in how ruminant’s unique reproductive systems evolved. Other studies focused on using interferon-tau to improve livestock fertility, but ultimately this interest fizzled out as researchers found fertility treatments for cows were cost-ineffective for producers and unappealing to the public.

The discovery of interferon-tau earned Roberts and his co-discoverer the Wolf Prize in agriculture in 2002. Some consider the prize an equivalent to the Nobel Prize since the Nobel prize does not regularly honor agriculturalists.

After the discovery of interferon tau, Roberts found another protein that impacts pregnancy, which formed the basis of a pregnancy test for cows. Roberts said it’s now a multi-million dollar product in the cattle industry.

Today, Roberts’ lab has moved to other developmental research. He started studying human placentas. His work focuses on preeclampsia, a condition which impacts 5-10 percent of all pregnancies and is caused by the placenta. Roberts’s lab has also developed new lines of pluripotent pig stem cells which are helping scientists learn how to regenerate eye and heart tissue. At age 77, he is still funded and active.

Roberts was featured as a guest editor in the November 2017 issue of Reproduction. He also wrote an editorial introducing the topic and summarizing each review, “30 years on from the molecular cloning of interferon-tau.”

Engineering the Immune System

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Chemical engineering students Caitlin Leeper and Rui Zhang work in Bret Ulery lab. The lab conducts innovative research combining chemical engineering with immunology.| Photo by Samantha Kummerer, Bond LSC.

 

Saturday Morning Science talks engineering our next defense

By: Samantha Kummerer, Bond LSC

Saturday Morning Science brings science to the people, bagels included. In an effort to highlight this outreach effort, we’re profiling a recent SMS speaker who talked about … well, read for yourself below.

Inside your body is a complex network of interlocking biological pieces. Tissues, cells and organs are consistently working together to defend against an outside attack. This is the immune system, the body’s natural defense mechanism, which is incredibly important to keeping us healthy but are we currently using it to its full advantage?

Chemical engineering Professor Bret Ulery feels we have gotten a good start, but overall the answer is still a resounding no.

“We have this unique opportunity to leverage the things that are going on to make a difference in the immune system,” said Ulery, the Assistant Professor of Chemical Engineering and Courtesy Assistant Professor of Bioengineering.

Ulery runs a lab within Lafferre Hall centered on creating designer biomaterials.

He describes biomaterials as any substance that carries out a biological function which are commonly created to avoid interfering with the immune system. They can be used to replace a knee joint, a heart valve, or even contact lenses to correct vision.

“That’s been very successful for a long time in certain areas but what if we want to tackle some grand challenges?” Ulery said. “We may want to rethink what we’re doing with biomaterials and how we design them.”

To take on these bigger problems, his lab leverages the chemical and physical properties of materials to facilitate unique biological functions in regenerative medicine and immunology.

Vaccines seemed a logical place to start. A vaccine introduces a portion of a pathogen to a patient so they can be exposed to just enough to create an immune response without developing the actual disease. Ulery explained a person does not get sick from a vaccine because it is designed to target both the innate and adaptive immune responses without having the capacity to induce illness.

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Traditionally, there are just a few ways to create a vaccine. First, scientists use heat or radiation to inactivate a pathogen. It is killed so the patient will not be exposed to the full disease but the immune response will still be triggered. While this type of vaccine is safe and easy to transport, the immune response it induces is weak and thus requires a great number and more frequent immunizations to be effective.

Another method is to keep the pathogen alive but to knock out its disease activity like what is done with the flu shot. Scientists take out part of the virus but keep it alive. This way the virus can still grow but won’t create the same degree of damage as the normal pathogen. Here, the immune response is stronger but not always equally effective in everyone due to differences in viral strains that have mutated to get around certain immune defenses.

Ulery wants to engineer more effective vaccines by only exposing the patient to the components absolutely necessary.

“We wouldn’t have to worry about any of this other bacterial gunk that would be with it. However, the problem there is the immune response is very weak because all that other junk actually plays a role in inducing the immune response, but it’s a lot safer, we can make it cheaper, make it easier to transport,” Ulery said. “We can do a lot of manipulation.”immune_system2

This manipulation involves taking a portion of a protein called a peptide and tethering a fat to it. This new molecule called a peptide amphiphile folds in water in unique ways to create interesting nanostructures called micelles.

“Instead of having some sacrificial material where we load our drug or vaccine into the core, this is actually a nanoparticle that is made almost entirely from the vaccine itself, so we get really high concentrations of the peptide and the vaccine,” he said, explaining the benefits.

By adding different peptides, the lab is able to create a vaccine that works for multiple types of infections. Ulery said his team is working towards applying these techniques to combat diseases such as Lyme disease, influenza and even cancer.

Current methods of targeting cancer are tricky because of the similarity between cancer cells and healthy cells. Ulery said it’s difficult to make a vaccine that just kills the unwanted cells.

Despite the challenge, Ulery and other researchers at MU think they found a molecule that is good at killing cancer cells without hurting healthy cells. Initial tests revealed engineered micelles can be used to deliver a peptide drug to allow patients to receive smaller doses because the treatment kills more cancer cells in a targeted area. Ulery explained the exciting part of this is the method does not require changing the immune response.

But what if the team did use the immune system to improve treatments?

The chemical engineer explained there are immune cells within a cancerous tumor. However, the tumor’s environment prevents the immune system from doing its job. Ulery believes it might be possible to retrain the immune system to kill cancer.

That method would be similar to how vaccines are created. Instead of modifying portions of a protein, scientists could modify tumor cells so the immune system could process them easier. That’s one possibility but an even better option would be making a vaccine specific to a patient. Ulery said this would be the third generation of immunotherapy where different therapies work for different areas.

Much of Ulery’s work at MU is just starting to touch the surface of its potential, but the lab continues to challenge traditional immunology notions as it aims to create better solutions.

Ulery’s spoke Sept. 30 as part of Saturday Morning Science. The series invites speakers in all types of science to speak every Saturday at 10:30 a.m. This outreach effort is free and open to the public. Find its schedule speakers at bondlsc.missouri.edu/saturday-morning-science/schedule.