Engineering the Immune System


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.


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

Kris Budd #IAmScience


Kris Budd, a Ph.D. candidate in Lori Eggert’s lab, works with Bond LSC to track elephant DNA in Southeast Asia. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because I have the ability to transform the fate of endangered species.”

If someone had told Kris Budd that she’d be investigating elephant feces on daily basis in her Ph.D. program, she wouldn’t have bought it. If they’d said she’d realize it’s a passion of hers, she would’ve been in shock.

As a third year Ph.D. candidate in Lori Eggert’s lab, Budd is able to do meaningful work that is helping endangered elephants through feces.

“I always wanted to work with an endangered species,” Budd said. “I’ve always been excited about this, and the more you find out about elephants, the more you love them.”

Budd receives samples of elephant dung from Southeast Asia, and singles out the elephant DNA from the other species present in the sample — most commonly microbes and insects, but sometimes even goats and humans.

“You have to be aware that there can be DNA from anything that walked by that day,” Budd said. “We have to use specific tools to make sure we just get the elephant DNA.”

“After processing, we use the DNA Core Facility in Bond LSC, which isn’t an easy task since we typically run hundreds of samples several times for a single study.” Budd said. “But they always do it with grace.”

Budd then uncovers the genetic makeup with the help of the Informatics Research Core Facility (IRCF) and meetings with members of Chris Pires’ lab in Bond LSC.

From there, Budd is able to input the DNA into a system and keep track of the elephants overseas. They, however, become way more than numbers to her.

“They might just be a sample in your data, but you get to know the elephants,” Budd said. “Elephants are so much more. There are so many different elements to them — genetics, behavior, and ecology. Their evolutionary history and family structure tells a story, all seen through feces.”

Her work is about to get a lot more hands-on next semester, as Budd will be traveling overseas to collect samples herself.

“We’re going in the spring and we’ll teach local technicians how to go about collecting samples,” Budd said. “We’ll collect a lot of samples of our own while we’re there, too.”

Budd will be able to determine what is happening with the elephant populations in Southeast Asia more closely then.

“There’s a big push with critically endangered species to translate data into something that can help them,” Budd said. “The samples I’m working on from Myanmar are actually an extinct population, but we want to re-wild similar elephants in the same location.”

Essentially, that would require Budd to find a genetically similar elephant population that would be most likely to thrive in the same environment.

While actually implementing the re-wild process won’t happen for a while, Budd is certain about the influence of Bond LSC in the elephant re-wilding’s future success.

“My work wouldn’t be possible without the people who work at Bond LSC,” Budd said.

A zebrafish’s empty stomach can help scientists understand brain function

A new test can show how much a zebrafish larva has eaten. This basic information could be crucial to upcoming discoveries.

A zebrafish swims in its tank. Understanding how zebrafish move  can give researchers insight into how certain diseases impact human motion.  Photo courtesy National Institute of Child Health and Human Development.

A zebrafish swims in its tank. Understanding how zebrafish move can give researchers insight into how certain diseases impact human motion. Photo courtesy National Institute of Child Health and Human Development.

By Eleanor C. Hasenbeck | Bond Life Sciences

Until now, it was hard to know when a zebrafish larva had a full stomach.

Researchers in Anand Chandrasekhar’s Lab at the Bond Life Sciences Center are studying the networks of neurons that control the zebrafish’s jaw, but to do that, they first had to figure out just how much these fish larvae eat.

They didn’t just need to understand it, they had to be able to test it. The successful development of a test that measures how well a zebrafish larva can eat has already lead to more discoveries.

To develop this test, researchers fed the larvae fluorescent fish food for three hours at a time. That’s just long enough for them to eat it, and just before their intestine starts to push it out. Their tiny, fluorescent bellies were examined under a microscope and scored. A zero meant that there was no food in the larva’s stomach, while a three meant the stomach was completely full.

With this feeding test under their belts, researchers are now able to form and test more research questions. The Chandrasekhar Lab used it to better understand networks of branchiomotor neurons, the circuitry that controls jaw movement. These neurons also control the gill muscles that move in automatic movements, such as breathing, just as neurons in the human brainstem allow us to breathe without thinking. Researchers look at the zebrafish’s very basic motor neurons to understand how these nerves develop, heal and control simple tasks.

One experiment tested how fewer branchiomotor neurons affect the action of eating. They destroyed 50-80 percent of the larvae’s branchiomotor neurons using a chemical-genetic method. The fish with fewer branchiomotor neurons also ate less food. They tried a similar experiment, but this time using lasers to remove only a select portion of branchiomotor neurons that controls a set of jaw muscles. Again, they found that the larvae that went under the laser were not able to eat as much food as the normal larvae. Finally, they conducted the food-intake test with mutant larvae that did not have any cranial motor neurons. As the researchers predicted, the mutants were not able to eat.

Now, they want to test how these animals eat when these neurons develop differently. While the first tests essentially smashed nearly all of the zebrafish’s branchiomotor neuron circuitry, their upcoming research will examine what happens when these circuits are wired in a different way, with neurons in the wrong spots. They’ll be looking at much subtler changes, Chandrasekhar said.

“If they don’t eat properly, do they move their jaw properly? That’s the next question that I want to answer,” said Emilia Asante, a doctoral candidate in the lab. “Are the axons not going to the right position? Are their neuromuscular junctions not properly positioned? Are there fewer of them in the mutant? There are all these questions that these assays are actually critical in answering.”

Asante is also working to make the feeding test more quantitative and less labor intensive. In its current form, someone has to look at each larva and judge if the food in its stomach makes it a zero, one, two or three. They want to be able to measure more accurately how much food is in the fish’s belly. If they were able to develop a faster and more accurate test, researchers would be able to rapidly measure food intake in a greater number of fish and to test the effects of many different chemical and environmental factors.

Zebrafish are a unique lab animal model used in research for a number of reasons. They’re easy to observe because the embryo develops quickly in an egg outside of the mother. They’re transparent, so researchers can make certain cells visible using florescence and observe them in a developing animal without killing it. Their genome is fully sequenced, so researchers can easily create mutations in specific genes using CRISPR technology.

“Many of the same circuitry that you find in humans are also there in more primitive organisms, and one of them happens to be the zebrafish,” Chandrasekhar said. “It has got some of the same types of neurons and the same types of circuits that you can find in humans.”

Research into the zebrafish’s neural networks can help researchers understand diseases like Amyotrophic Lateral Sclerosis, better known as Lou Gehrig’s disease, which causes a loss of function in a human’s motor abilities, including those of the branchiomotor neurons.

This study “Role of branchiomotor neurons in controlling food intake of zebrafish larvae” was recently published in the Journal of Neurogenetics.

Lisa Caesar #IAmScience


Lisa Caesar is a biological sciences Ph.D. candidate who works in Laura Schulz’s lab. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because education and my pursuit of learning became my ticket out of poverty and a way that I can really help others.”

“Mother knows best” rings true for Gerialisa Caesar. In her family, the career options were either to be a lawyer, engineer or doctor.

But with little interest in law and a greater love for science than math, Caesar decided to pursue her doctorate.

“I graduated high school at 16 fully equipped to enter the work force,” Caesar said. “I went back to school to study science because my mom basically told me I had to, but biology fit me really well, so it worked out.”

Initially, Caesar was hesitant that she could even become a scientist.

“I had an idea of what a scientist was, and it wasn’t me,” Caesar said. “After I immigrated from Guyana, my undergraduate advisors, Drs. Carroll and Catapane, explained the opportunities I had to study biology. It opened the world of possibilities for me to pursue science.”

Now, as a biological sciences Ph.D. candidate in Laura Schulz’s lab, Caesar focuses on women’s health and reproductive biology.

“My research is to understand how a mother’s nutrition prior to and during pregnancy affects the baby’s development,” Caesar said. “This is important as several studies link maternal diet during pregnancy to an increase in susceptibility of the offspring developing diseases such as obesity, diabetes and hypertension in adulthood.”

That includes connecting how mother’s diets cause fetal health issues, which is a highly debated topic.

“For example, a lot of women are told to take folic acid pills during pregnancy,” Caesar said. “Doing that has been tied to help with neural development concerns — things like spina bifada [a birth defect that affects developing babies’ spinal cords]. Understanding the mechanisms that make that occur would aid in developing better interventions to prevent such occurrences.”

As a result, Caesar’s research has the ability to help the world’s greatest health concerns in an impactful way.

“My work is directly contributing to prevent health issues that exist for future generations,” Caesar said. “Knowing that is motivating.”

After she earns her Ph.D., Caesar would love to work for the Center for Disease Control and Prevention.

“The CDC has immediate response teams that react to major disease concerns. Being a part of that would be incredible,” Caesar said. “There’s something about working for the CDC and being able to have a meaningful impact within the community that calls me.”

Caesar plans to channel that passion regardless of where she ends up, though.

“Biology is literally the study of life,” Caesar said. “As much as I thought science was challenging, I am able to see how it affects everyday life. I have a purpose, and I know what I do is going to make a difference.”

Dr. Burke wins Distinguished Professor Award

Donald Burke-Agüero

Donald Burke-Agüero stands in his office in Bond LSC, holding a model of an RNA protein structure. Burke-Agüero studies the bio-chemical functions of RNA, and how those functions might be able to be artificially designed or replicated. | Phillip Sitter, Bond LSC

By Samantha Kummerer, Bond LSC

“He’s a triple threat in science,” Bond Life Sciences researcher David Pintel said.

Donald Burke’s combination of scientific excellence, caring mentorship and devotion to the University of Missouri led Pintel to nominate Burke for the 2017 William H. Byler Distinguished Professor Award.

The university agreed, awarding him the honor in October.

The University-wide accolade recognizes a faculty member for their “outstanding abilities, performance, and character.” When Pintel read this description he said he instantly thought of Burke.

This is the first time a faculty member from Bond LSC has won the award. Pintel said the award shows the quality of people here and the department is proud of him for receiving it.

Burke is a Molecular Microbiology & Immunology professor. His lab in Bond LSC studies RNA, the molecule used to help cells copy genetic information from DNA.

For Burke, the award is an honor.

“You always try to do everything you can to contribute to making the place great and you don’t do it for the purpose of being recognized, yet when the recognition happens, it’s nice,” he said.

Burke’s lab hosts students from the high-school to post-doctoral level. For each member, Burke said he tries to figure out their motivation. He starts by just asking questions and is able to align their goals and his.

“You can’t just say ‘This is what we do in my lab, deal with it.’ You can’t do that,” Burke elaborated, “Yes, it’s a lot of work and a lot of effort, but it has ceased being a burden for me. Now, I think of it as a new fun challenge.”

He said that challenge has paid off because every student that has gone through his lab has taken his science in new directions.

Pintel said this connection Burke has with his students is easy to see.

“People in his lab love him and, to me, that’s always a good sign,” Pintel said. “When I see people in a lab like that, I know it’s a good environment. That always means something good is going on.”

During their time in his lab, Burke tries to teach his students the importance of working as a team as well as learning understand the research process.

“Some of the things I’m most proud of aren’t necessarily the most impactful research, but the things where I know the struggle that went into solving the puzzle that was in front of us,” he explained. “The thrill of the chase may not be as interesting to the rest of the world but you know how hard that person worked and how many false leads there were.”

Recently, Burke has expanded his passion for motivating others to a new area. In July, Burke became the Interim Chair of Molecular Microbiology & Immunology.

“Now that he’s the interim chair he is trying to provide the same kind of supportive environment for the department that he’s been doing for his lab,” Pintel said.

Burk said he wants to help other faculty members achieve their goals and prioritize tasks. He is also involved in a new faculty search where he works to ensure the applicant pool reflects those that might be wanting to apply by removing language that may prevent people from applying.

“Again, I want to help find what obstacles can be in their way and get rid of those before it slows them down,” Burke said restating his passion for helping others achieve excellence.

Donald Burke-Aguero is an MU professor in the Department of Molecular Microbiology & Immunology. He received his bachelors’ degree from the University of Kansas and his Ph.D. from the University of California, Berkeley. Burke joined the MU community in 2005.

Julia Brose #IAmScience


Julia Brose is a senior studying biochemistry at Mizzou. She works in Chris Pires lab in Bond LSC. | Photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because I really enjoy discovering and being around people who cultivate a positive learning environment.”

As a freshman at Mizzou four years ago, Julia Brose knew she had a love for plants. That, however, competed with her fascination with biochemistry.

Luckily, she found and was selected for FRIPS, Freshman Research in Plant Sciences, which allowed her to do both. The program is made up of 10 freshman each year who gain valuable hands-on research experience with plants.

“I started working in Bond LSC, and that’s really where I found my love for research,” Brose said. “Working with plants allowed me to explore that interest, while still majoring in biochemistry. I have the best of both worlds.”

Her degree in biochemistry coupled with her research experience has given her a number of unique opportunities. One of which was being a Cherng Summer Scholar at Bond LSC last summer where she studied plants and their protein makeup.

“I was looking at amino acids, which are the building blocks of proteins in plants,” Brose said. “Specifically, I was looking for the content in seeds within Brassica, a species that includes cauliflower and kale.”

Another unique opportunity Brose earned was in summer of 2016. She worked at Stanford University as part of a fellowship for the American Society of Plant Biologists.

“I studied novel plant defense compounds —how plants protect themselves,” Brose said. “People can move around and gain protection that way, but plants need different chemicals to protect themselves.”

Her background in biochemistry and her experience with plant research at Bond LSC in Chris Pires’ lab provided her with the ability to analyze the defense structures in a unique way. As a result, she uncovered something that others had either ignored or overlooked.

“I found that the chemicals we see in leaves are in roots, too,” Brose said. “No one else had looked there before, so it was cool to be the first.”

Her work at Stanford led them to send her to a conference in Hawaii earlier this year. While there, Brose was able to present a poster on her findings as well as network with a number of successful scientists in a variety of fields.

As she nears graduation this spring, Brose has begun looking into graduate school options. Those are largely based upon the experience she had in Hawaii.

“I was able to make connections that have influenced my plans for the future as far as where I’m applying to graduate school,” Brose said.

Wherever she ends up, Brose hopes to teach.

“I like mentoring students and being around a learning environment,” Brose said. “That is really fostered in a university.”

Marianne Emery #IAmScience


Marianne Emery is a Ph.D. candidate in Ruthie Angelovici’s Lab in Bond LSC. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because it leads to innovation that makes for a better world, which is an awesome thing to be a part of.”

It’s good to have a role model, and Marianne Emery has always looked up to female pioneer scientists.

One of her favorites is Barbara McClintock, a Nobel prize winning botantist who studied how the chromosomes of corn change during reproduction.

It is from women like McClintock that Emery is encouraged to always be impactful with her research and overcome obstacles with grace.

“I think it’s inspiring to see these women in positions that have typically been male-dominated,” Emery said. “You lose your confidence sometimes when things just don’t work. You’re continuously met with obstacles, but you have to keep going.”

And that she has.

Emery works in Ruthie Angelovici’s lab at Bond LSC to understand what controls protein levels in seed. She primarily spends her time on the computer working with large data sets and trying new software, but is always excited about the findings she’s able to uncover.

“I enjoy developing new skill sets every day,” Emery said. “The most important thing I’ve learned so far is how to communicate my science and how to communicate when I’m having an issue. Conveying a problem and problem-solving in general can be hard.”

Still, Emery continues to focus on improving on a daily basis. She hopes to work for a company like Monsanto after earning her Ph.D.

“I really like the business side of science,” Emery said. “Ultimately, a bigger company would be the best fit. I also really like policy and the patenting process.”

Wherever Emery ends up, though, she hopes to become like the women who pioneered science.

“Female scientists have been so inspiring to me,” Emery said. “I hope that one day I can be a leader and a role model for other young women who aspire to be involved with science.”

The Truth Behind BPA- Free Labels

Cheryl Rosenfeld

Cheryl Rosenfeld, a Bond Life Sciences Center investigator and professor of biomedical sciences at the University of Missouri. | photo by Jinghong Chen, Bond LSC

What companies aren’t telling you about their merchandise

By: Samantha Kummerer, Bond LSC

Bisphenol A, otherwise known as BPA, is used to make plastic containers, coats the inside your metal food cans, and leaches into your food and water.

BPA has concerned scientists, health practitioners and the general public for many years because of its potential to mimic hormones and disrupt the developmental stages in animals.

Opposition to the chemical has led to certain manufacture’s marketing their items, such as food containers and water bottles, as“BPA–Free” and a global push to reduce the usage of BPA in commonly used household-items.

However, new evidence suggests consumers may not be as ‘free’ from harm as they think.

Bond Life Sciences Center researcher Cheryl Rosenfeld suggested that many consumers might not be aware of how these alternatives are made. BPA-substitutes — bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) — aren’t too different from BPA chemically.

“They’re just playing with various synthetic structures is what many industrials groups are doing,” she said.

BPA is made up of two chemical compound groups called phenols. Picture two rings with different elements connected. In BPF, BPS and BPAF all those same parts are still present, and the only change is that the rings are rotated differently and contain various branching chemicals .

Since these alternate chemicals are structurally similar to BPA, they still bind to estrogen receptors, receptors to which the natural hormone estrogen binds and activates, which results in up- or down-regulation in the expression of various genes.

“The worst problem is that humans and animals are unknowingly serving as test subjects. Industrial companies are not required to show definitive evidence that these alternatives to BPA are safe. They can cite their own limited studies, but currently, no rigorous testing is required for these BPA-alternative chemicals that are being to flood the market. There is no requirement for the products that contain these chemicals to state as such. Thus, consumers cannot make educated decisions when purchasing various food and beverage products,” Rosenfeld said speaking of the industry.

Substitutes aren’t always better

Rosenfeld recently published a literature review exploring the use of the BPA-alternatives and their potential risk. She began the work out of curiosity since her Bond LSC lab studies the harmful effects of BPA.

After putting the puzzle pieces together, the big picture began to emerge that exposure of rodent models to these substitute chemicals exert analogous effects as BPA — depressive behaviors, increased anxiety, decrease in social behavior and decreased maternal/paternal care. In some cases, the alternatives have an even greater effect, according to Rosenfeld.

Understanding BPA

Production of the industrial chemical, BPA, began in the mid 1900’s to make plastics. Today, it can be found in everything from water bottles to storage containers and even food. With this increase exposure comes an increased risk to consumers.

Past studies linked exposure to the chemical with health effects on the brain and behavior and many other widespread effects.

When BPA enters the body, the can at least partially metabolize and break down the chemical via enzymes, which is then removed from the body. But there is a limited supply of such metabolizing enzymes used and those consuming BPA daily will end up overwhelming their body’s ability to metabolize and eliminate it with the net effect that BPA can accumulate over time and continue to exert potential harmful effects.

The most serious effect of BPA and now the substitutes happens during development. Fetuses have poorability to break down the chemical. Evidence links BPA exposure during development with neurological disorders like autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD).

Most studies have examined the effects of BPA alternatives in rodents and zebrafish. While numerous factors prevent scientists from establishing causation in humans, Rosenfeld suggested it is time to at least start correlating early life exposure to BPA alternatives and risk of neurobehavioral disorders, including ASD, ADHD, and other neurodegenerative disorders.

“What’s worrisome is the women who are seeking to become pregnant or are currently pregnant, they are under the impression that they are making positive choices for their sons and daughters by using BPA-free products, but such products likely contain these BPA-substitute chemicals that can result in equal and possibly even greater negative consequences for their unborn offspring. Ultimately, the question is then what sort of products should be using?” Rosenfeld explained.

Humans aren’t alone in the impact. Rosenfeld explained these chemicals don’t break down in the environment and could play a part in the decline of certain animals. Previous studies by Rosenfeld’s lab and others at MU revealed BPA has the ability to feminize what should otherwise be male turtles.

“I just wish we could stop and pause and think about the havoc we are wrecking on our own environment and ourselves,” she said.

Without definitive results, a lot of unanswered questions remain. Future studies will likely explore the full range of effects caused by the BPA alternatives. Rosenfeld is calling for researchers to begin to treat these alternatives like BPA and put them through rigorous studies. These studies, however, come with a cost.

Rosenfeld’s lab is funded for BPA research. To add these additional chemicals to her current studies, the cost would double and triple due to the increased amount of animal test subjects that would be required.

“They keep upping the bar of how many replicas we have to test. If you want to show effects, if you want us to believe your results, we have to test 12-15 animals, well then you need to test another 12-15 animals in these groups and then your research dollars are all-of-a-sudden gone,” Rosenfeld said.

Research costs are going up and in the meantime BPA is still being produced in high quantities, so the industry as a whole has to decide where to allocate its funds.

“It’s a moving target. We’re trying to keep up and they keep synthesizing more and more chemicals everyday. The problem is we are completely outspent in terms of avaibable research dollars compared to the money industrial companies have on hand to fight tighter reguation. It’s not even a fair fight,” she said.

Rosenfeld hopes this new publication prompts scientists and the public to begin to question and call for more action on testing these pervasive BPA subsitutes. The silver lining is even though we can’t control our exposure to these chemicals, Rosenfeld hopes we might be able to find a way to combat our exposure.

Cheryl Rosenfeld is a Biomedical Sciences professor,a researcher in Bond Life Sciences Center, and research faculty member in the Thompson Center for Autism and Neurobehavioral Disorders. Rosenfeld specializes in how the early in utero environment can shape later offspring health, otherwise considered developmental origins of health and disease (DOHaD)She earned her bachelors and doctor of veterinary medicine degrees from the University of Illinois and her PhD from the University of Missouri.

In a viral game, the fight isn’t fair

Lab explores how parvo wins in tug of war with cells


Kinjal Majumder and David Pintel examine the protein levels in mouse cells during MVM infection. Each black band represents the amount of viral protein in infected cells over time. | Photo by Samantha Kummerer, Bond LSC

By: Samantha Kummerer, Bond LSC

At the start of any tug of war game, the battle is even. But it doesn’t stay that way for long. After a back and forth, the inevitable happens — the stronger team gives the rope one last tug and send the losers toppling over, claiming their dominance.

This is a game cells and viruses know well. In their version of tug of war, the virus eventually overtakes the cell and not only topples it but causes a consequence far worse than a few scraped knees.

This is how post-doctoral fellow Kinjal Majumder thinks of the interaction between parvoviruses and the dividing cells it conquers.

Majumder and others in the lab of David Pintel at Bond Life Sciences Center recently gained insight into how the virus achieves victory over the cell. These findings could improve human therapies and even play a role in treating cancer.

Meet the Champion

Parvoviruses are some of the smallest, simplest viruses. With only two genes, it has fewer DNA base pairs than most other viruses, up to ten times smaller in some cases. The virus’ size and simplicity, however, do not make it any easier to understand.

Pintel’s lab works at the “nitty gritty” level of the virus to study its basic molecular mechanism.

The group understands a little about how the virus operates but is working on the why.

Like a sly culprit, the virus uses its tiny nature to sneak inside the cell. The cell recognizes the presence of the virus as a foreign piece of DNA and responds to try to remove it. Once the cell responds, the virus begins replicating inside until it overtakes the cell. But, the tug of war game ends up more one-sided, so perhaps viewing the virus as a ruthless conqueror would be more accurate.

Latest Developments

Majumder’s experiments specifically focus on DNA damage response, an intrinsic function of cells. The DNA damage response constantly works to protect us from cancer by continuously repairing broken DNA to prevent harmful mutations in cells . This response uses a network of cellular pathways to monitor and provide checkpoints in the cell cycle to prevent damage from being passed on to the next generation of cells. But parvoviruses also tricks cells to begin a DNA damage response, which they use to eventually take over the host cell.

In July, the lab published the latest finding from a series of papers exploring a type of these parvoviruses called minute virus of mice (MVM). The discovery began when the team found that the virus stops cells from dividing within infected cells.

To do this, MVM uses the DNA damage response to stop cells from dividing, but still allows virus replication to continue. The group developed a system to examine how the virus took over the cell. Further experiments revealed the virus transcriptionally regulates cell cycle genes.

The team used CRISPR to target a cellular gene that the virus must inactivate for it to replicate. Expression of this gene is required for the cell to divide. They discovered the virus actually blocks the transcription of this gene so it cannot make its protein. Blocking this function also prevents the cell from dividing. Without cell division, the virus is free to rapidly replicate inside the cell.


Post-doctoral fellow, Kinjal Majumder, points to the results of a recent experiment. When MVM is mutated at particular sites, the protein levels produced by the virus decrease, but the virus continues to replicate efficiently. | Photo by Samantha Kummerer. Bond LSC

Majumder said parvo’s manipulation of infected cell cycles is different from other viruses because it can only replicate in cells that are actively synthesizing DNA. It eventually halts the process of cell division in infected cells by dysregulating transcription factors that regulate cell cycle gene expression. That’s what makes this discovery unique.

Endless Possibilities

This discovery only scratches the surface.

Majumder said the lab constantly thinks of new experiments to explore parvovirus biology. The simplicity of its DNA expedites the process of culturing and growing the virus, leaving more time for what Majumder calls the “fun experiments.”

“We try to be thorough and confident of our findings, so we attack experiments from many different angles,” Majumder said.

Imagine viewing an object from multiple angles under varying light conditions. The change in perspective reveals something different about it with each new look. This approach expands their understanding of parvoviruses.

Majumder explained the lab makes use of everything from high-resolution imaging and CRISPR technology to proteomics and deep sequencing to study the tug-of-war between MVM and the DNA damage response.

“The thing about being a postdoc is you kind of have to be a jack of all trades,” Majumder said about his ability to conduct the range of experiments.

Happy CellSnapshot1.jpg

Parv O’Lantern: A nucleus of an infected mouse cell is captured using a super-resolution GSD microscope. Parvovirus MVM creates replication centers within host cell nuclei. The viral DNA can be labeled with fluorescent probes for imaging. Viral genomes that haven’t made it inside are illuminated on the edge. The viral genomes that have entered made replication centers that resemble the face of a Jack O’Latern. | Photo by Kinjal Majumder and Alexander Jurkevich

Wider Implications

While parvoviruses are not a deadly threat to humans, understanding it has major implications for humans.

Parvoviruses are used to develop gene therapy tools to treat disorders like muscular dystrophy and spinal muscular atrophy. The Pintel lab collaborates with labs such as the Lorson and Sarafianos lab in Bond LSC, to explore its therapeutic potential.

Majumder explained the lab is also interested in understanding how the virus could improve cancer treatment. Parvo’s tendency to replicate in dividing cells links it to how cells divide uncontrollably in cancer. Majumder explained those scientists are trying to use that function of the virus to target cancer cells.

This makes work in the Pintel lab that much more important. But, before the virus can fully improve humans’ conditions, researchers better grasp its capabilities. And that means more of the daily experiments within the Pintel lab.

“What we learn from studying a simple virus can be expanded to more complicated viruses because there are some viruses that can make a dozen different proteins, so that’s a more complicated system,” Majumder said. “Before you can get to the more complicated systems, you need to be able to understand the one that makes just a few proteins.”

For now, scientists will play their own tug of war as they go back and forth in their findings and experiments to uncover the mystery surrounding this small, unique virus.

Vivek Shrestha #IAmScience

Vivek Shrestha

Vivek Shrestha, a Ph. D candidate, works in Dr. Ruthie Angelovici’s lab at Bond LSC. | photo by Allison Scott, Bond LSC

By Allison Scott | Bond Life Sciences Center

“#IAmScience because it provides me with a platform to make that which seems impossible possible.”

Agriculture is a mainstay in Nepal, where Vivek Shrestha was born and raised. He grew up in a small farming family, but he was surprised that although a significant portion of the country was involved with agriculture, food insecurity was prevalent.

“Nepal is a small, developing nation that is naturally beautiful,” Shrestha said. “Agriculture is huge, but still a lot of people are food insecure.”

Shrestha saw this need and decided to study plant sciences as an undergraduate at Tribhuvan University in Nepal. From there, he earned his master’s degree from South Dakota State University before coming to Mizzou to pursue his Ph.D.

“The overall goal of my study is to understand the genetic architecture of seed amino acid composition,” Shrestha said. “Seed amino acid composition is a complex metabolic trait and, despite having tremendous importance in biofortification efforts in seed crops, the underlying genetics are not clearly understood.”

Currently, Shrestha works in Dr. Ruthie Angelovici’s lab at Bond LSC studying the trait to better grasp its genetic breakdown.

“The {research} quality of amino acids has a tradeoff with the quantity, which makes it more challenging,” Shrestha said. “However, our research is of paramount importance because it has millions of beneficiaries.”

Shrestha’s research helps not only with food stability in places like Nepal, but also in cutting costs for the livestock feed industry in developed nations like the United States.

“Maize is a huge part of the feed industry for the United States,” Shrestha said.

This dual interest makes Shrestha’s work that much more rewarding. Although the amino acids are complex — having multiple cellular processes and interactions — the complexity gives Shrestha motivations and excitement in what he does.

“Every day is a fresh, new day for me to explore and enjoy science,” Shrestha said.