Yesterday, Tom Spencer, MU’s interim vice chancellor for research and economic development, officially named Bond LSC Interim Director Walter Gassman to the permanent director role. Below is Spencer’s announcement.
Today, I am pleased to announce that Walter Gassmann, professor in the Division of Plant Sciences and a member of the Interdisciplinary Plant Group, has agreed to serve as director of the Bond Life Sciences Center (LSC) effective this month.
Walter stepped into the role of interim director at Bond LSC July 1, 2017. Since then, his leadership has guided the center in its mission, and we have appreciated his steady hand as the center and the Office of Research and Economic Development adapted to funding changes. Walter’s stepped-up emphasis on the research enterprise is helping to address our systemwide focus on increasing research and creative endeavors.
Bond LSC’s culture enables 27 faculty investigators from 12 academic units to solve problems in human and animal health, the environment and agriculture. The collaborative, interdisciplinary nature of the work conducted at Bond LSC is a sound model for NextGen Precision Health. Basic and advanced research conducted at the center and the partnerships formed will figure prominently in advancements made in fundamental discovery and translational medicine.
Dr. Gassmann has been an active scientist at the center since its inception, and his collaborative research focuses on the inner workings of the plant immune system, in particular, how it is activated and kept in check to prevent harmful side effects from overactivity. His lab will continue its work as he officially moves into the permanent director role. Read more about Walter and his accomplishments here.
Sincerely, Tom Spencer Interim Vice Chancellor for Research and Economic Development
Crops resist bacterial leaf blight; ruling clears path to provide smallholder farmers with a safe, affordable option for preventing destructive disease
Columbia and St. Louis, MO, October 14, 2020 – The Healthy Crops team, with support from the Bill & Melinda Gates Foundation, have used gene editing tools to develop new varieties of disease-resistant rice that regulators in the United States and Colombia have determined are equivalent to what could be accomplished with conventional breeding. Bacterial blight can reduce rice yields by up to 70 percent, with the heaviest losses typically experienced by smallholder rice growers in low and middle-income countries. This has a profound impact on farmer productivity and economic mobility. The Healthy Crops team turned to gene editing to develop disease-resistant varieties as a way to provide farmers with a safe, affordable, effective solution.
“We first set about to understand the gene the bacteria use to make the plant vulnerable to its disease,” said Bing Yang, PhD, a researcher with the University of Missouri Bond Life Sciences Center professor, Division of Plant Sciences and member, Donald Danforth Plant Science Center in St. Louis. “We then used our CRISPR technology precisely to remove the element in the gene to avoid the pathway the pathogen takes that makes the plants susceptible to blight.”
The team used gene editing to create rice lines in elite varieties that are comparable to naturally occurring variants. These lines can resist infection by bacterial leaf blight, which leads to major losses for one of the world’s most important food crops. The rulings from the United States Department of Agriculture (USDA) and the corresponding authority in Colombia, the Instituto Colombiano Agropecuario (ICA), clear the way for field tests to select the best material for distribution to breeders in the U.S. and Colombia.
The improvements were accomplished via gene editing, which did not introduce any DNA into the plants and focused on “promoter regions” in three genes that are targeted by the causative agent of rice blight, the bacterium Xanthomonas oryzae pathovar oryzae. The research was described in an article in Nature Biotechnology in 2019.
Yang is just one member of the research consortium, headed by Humboldt Professor Wolf B. Frommer from Heinrich Heine University Düsseldorf (HHU), that has worked more than four years on this research. Six research institutions on three continents were involved including the University of Missouri, Donald Danforth Plant Science Center, University of Florida, the Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT) in Colombia, the Institut de Recherche pour le Développement (IRD) in France and the International Rice Research Institute (IRRI) in the Philippines.
In the wake of the ruling from U.S. and Colombian officials, the new blight-resistant varieties can now be used to introduce the resistance trait into many different types of rice via standard breeding strategies. Additional testing and breeding work is expected to take place in multiple locations that are favorable for growing tropical rice varieties.
“It’s exciting to use science and technology to do to help farmers protect and improve their rice production,” Yang said. “We hope to work closely with the local institutions in the next phase to introduce these into the varieties of rice small farmers use.”
The Healthy Crops Team has no commercial interest in its work. Its goal is to ensure disease- resistant rice varieties are accessible and affordable, especially for smallholder farmers who depend on rice production to support their families.
About The Donald Danforth Plant Science Center
Founded in 1998, the Donald Danforth Plant Science Center is a not-for-profit research institute with a mission to improve the human condition through plant science. Research, education and outreach aim to have impact at the nexus of food security and the environment, and position the St. Louis region as a world center for plant science. The Center’s work is funded through competitive grants from many sources, including the National Institutes of Health, U.S. Department of Energy, National Science Foundation, and the Bill & Melinda Gates Foundation. Follow us on Twitter at @DanforthCenter.
About Bond Life Sciences Center
Founded in 2004, the Christopher S. Bond Life Sciences Center was designed with teamwork in mind, fostering collaborations between scientists of diverse disciplines and backgrounds. From cancer and HIV to plant science and informatics, our researchers work together to move basic science forward and lay the groundwork for a better world. Learn more at bondlsc.missouri.edu.
Bisphenol A, more commonly known as BPA, has been a source of scientific dispute for the past decade. With a lack of consensus among scientists, consumers are left unaware of the potential harms of the chemicals in plastic.
In response to a recent report by the Food and Drug Administration (FDA) that claims BPA is safe at the current levels occurring in foods, Bond Life Sciences Center principal investigator Cheryl Rosenfeld and a group of researchers across the country have teamed up to release a secondary analysis of the existing data, which disputes this claim.
The industrial chemical is used in manufacture of plastics and resins, and it is commonly found in plastic food containers, water bottles, food can linings and other consumer products. BPA can leach out into water supplies and food where humans and wildlife may be exposed to this ‘persistent chemical’ by ingestion or inhalation.
All of the researchers on the second report were a part of the original team put together by the FDA to study the effects of BPA. However, many researchers on that team disagree with the FDA’s re-analysis and interpretation of their individual findings.
By using the publicly available data published on the National Toxicology Program’s website, these scientists reevaluated the information originally compiled by Rosenfeld and dozens of colleagues as part of a Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA).
Cheryl Rosenfeld had concerns of this Consortium project from the beginning.
“The idea at the outset was that individual investigators and FDA scientists partner together to address the question as to the safety of BPA, but even at the initial meetings, several concerns were raised,” Rosenfeld said.
The major source of disagreement boiled down to lab procedures, statistical analysis and a lack of regard for the inter-related effects of BPA on possibly multiple target organs and bodily functions. Going into it, the researchers had minimal input into the general experimental design, including a rat model that may be less sensitive to the effects of this chemical, the dosages of BPA that were tested, the fact that BPA was administered by what many consider a stressful procedure, oral gavage, and the period of administration.
One problem that was not thoroughly considered is the potential for nonmonotonic effects of BPA. That essentially means BPA shows adverse effects on the body at low and high doses, but not in between or middle-of-the-road doses.
On top of discrepancies over the research procedures, the researchers criticize the FDA for using stringent statistical analysis that may filter out important differences between groups.
“It’s like a metaphor about dropping your keys in a parking lot and looking over by the curb for them because there’s better light there,” said Gail Prins, a professor at the University of Illinois – Chicago and a collaborator on the original and secondary research project. “They’re concluding that BPA is not significant, but they’re not looking in the right places for significant results.”
In statistics, there are type one and type two errors. A type one error concludes that the results of the study were statistically significant when they’re not. Vice versa, a type two error concludes that the results are not statistically significant, but they are. Also, margin of error comes into play. P-value — a measure of deviation that determines which results are noteworthy — sets the stage for what is considered significant. Based on the method of a study, researchers can have stringent requirements for assessing the significance of a result (p≤.01), but most research uses p≤.05.
In simpler terms, p≤.05 allows researchers to be 95 percent certain that a result is meaningful. While the FDA used a p-value of <0.05, the researchers in the secondary study believe that the FDA failed to look at the statistical significance of the inter-related effects of BPA on multiple parts of the body, including the mammary glands, ovaries, kidneys, the prostate gland and cognitive-behavioral function.
Additionally, the statistical approaches the FDA sought to use would require hundreds of research replicates to be statistically valid. The FDA only had a budget to repeat the experiments up to 12 times per group, which some investigators questioned whether findings on these alone, especially with the methods the FDA sought to use, would provide meaningful results.
In 2012, the FDA banned the use of BPA in baby products, although that decision was largely due to public concern. However, the primary route of exposure to the effects of BPA are before babies are born. Since BPA is present in products used by pregnant mothers, it can lead to the development of health problems in babies including cancer later on in life.
The original statistical analysis for Rosenfeld’s portion of the project was done by Mark Ellersieck of MU, who has 30 years of experience, and a statistician with the FDA. When the analyses disagreed with each other, a neutral third-party was brought in to review the approaches used by Ellersieck and corroborated they were appropriate for the study design.
Now, Jiude Mao, a research scientist from the Division of Animal Sciences in Rosenfeld’s lab at Bond LSC, is working with Rosenfeld to reanalyze the results of the original study.
“I downloaded the raw data package online,” Mao said. “If you look at the effects of BPA on individual organs versus combining them and looking at its effects on multiple organs, the picture is very different.”
By using special informatics approaches, Mao found that the lowest dose of BPA tested simultaneously led to multiple effects on various target organs in females including the ovaries, uterus, mammary glands, heart, and fat tissue. In males, the prostate gland, along with the heart and adipose tissue showed inter-related changes due to BPA exposure.
Mao and Rosenfeld have also linked multi-organ effects of BPA at two other doses, with all doses tested currently considered safe by the FDA. They examined these inter-relationships at three age ranges: 21 days of age, 90-120 days of age, and 180 days of age. To the investigators’ knowledge this is the first type of toxicological study that has linked such data obtained in multiple investigators’ laboratories and shown such complex relationships.
The data from these three doses of BPA and three age ranges clearly indicate that BPA affects on a single organ can radiate out to affect many other organs throughout the body. By tugging on one organ, BPA can damage intricate webs that connects organs to each other. Such inter-relationships between individual CLARITY-BPA investigator data have not been considered by the FDA.
While a consensus hasn’t been met between the two parties, a potential solution for the data analysis discrepancy could be looking to machine learning or ‘deep learning’ to avoid human error or bias. This would include inputting both data sets into a program that can assess what the similarities and differences are and why the two groups are achieving different conclusions. This approach would ensure more confidence in the accuracy of the results instead of choosing a side to believe based on human calculations.
For the researchers, reevaluating the data means providing the full scope of the effects of BPA on multiple parts of the body. It also means giving consumers the correct information so that they can make well-informed decisions about their health.
“I am concerned that government agencies are not providing the public the fully story as to how BPA exposure might affect various organs, especially in infants exposed to this chemical during pre- and post-natal development when they do not have the full capacity to metabolize BPA and their organs are developing at this time,” Rosenfeld said.
Rosenfeld was joined by Jerrold Heindel, Scott Belcher, Jodi Flaws, Gail Prins, Shuk-Mei Ho, Juide Mao, Heather Patisaul, Ana Soto, Fred vom Saal and Thomas Zoeller from the Healthy Environmental and Endocrine Disruptor Strategies Commonweal, North Carolina State University, University of Illinois at Urbana-Champaign, University of Illinois at Chicago, University of Cincinnati College of Medicine, University of Missouri and University of Massachusetts at Amherst in this data reevaluation. Read more of their secondary results at the Journal of Reproductive Toxicology and see the original FDA CLARITY-BPA publication at FDA.gov.
A Bond Life Sciences Center researcher has been inducted into an elite organization comprised of two percent of all medical and biological engineers.
The American Institution for Medical and Biological Engineering (AIMBE) this week announced the induction of Dong Xu, a Bond LSC principal investigator and Shumaker Endowed Professor in the University of Missouri’s College of Engineering.
“Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer,” said Kamrul Islam, chair of the college’s Electrical Engineering and Computer Science department.
Xu was selected for his “distinguished contributions to bioinformatics and computational biology, and extensive services to University of Missouri and his research community.”
In addition to his endowed faculty position, Xu serves as director of the Information Technology program, whose core facility is housed in Bond LSC.
Membership to AIMBE’s College of Fellows recognizes those who have made outstanding contributions to engineering and medicine research, practice or education, and to those pioneering new and developing fields.
Because of health concerns, AIMBE’s annual meeting and induction ceremony scheduled for this spring was canceled. Under special procedures, the induction was held remotely.
You might be familiar with the idiom “don’t bite the hand that feeds you,” but when it comes to a certain lineage of tame Russian silver foxes it’s quite literal.
After more than 50 generations of breeding, these tame foxes likely offer insight into how selective breeding leads to domestication, and scientists dove deeper to look at what this trait might mean in terms of changes in the brain and the genes behind them.
“These silver foxes act like domesticated dogs and are assumingly a good model to look at the process of domestication, tracing what happened as the wolves became domesticated into what we recognize today as the domesticated dog. Wouldn’t that be fascinating to know all the things that coincide with that?” said Cheryl Rosenfeld, a Bond Life Sciences Center principal investigator at the University of Missouri and co-lead author on the study. “Presumably, to become domesticated the one biggest organ that would have to change is the brain, because that’s where fearfulness, aggression, and social behaviors emerge from, so my interest is in the brain and how various factors might affect it.”
The path away from aggression
While this story eventually focuses on the brain, the path to a modern model of tameness starts in Soviet Russia in the 1950s.
Russian geneticist Dmitry K. Belyaev bred hundreds of foxes in Siberia, initially selecting them based on their willingness to approach humans in their cage. In its beginning only 10 percent of those tested showed a weakened wild response, and those foxes were bred together to reinforce this docile nature. In later generations, their behavior was further evaluated based on their likelihood to interact with humans approaching their cage, their territorial behavior, response to attempts to pet them and reaction to the experimenter leaving the interaction. Lyudmila Trut, his intern now in her 80s and an author on this study, continues the breeding project.
“Those that showed a muted wild response would get bred together, so with each passing generation, the foxes showed diminished fear response. Once they established this tame fox population, they eventually developed the aggressive ones doing just the opposite in that they paired those foxes showing the most aggressive responses to an experimenter approaching the cage,” Rosenfeld said. “They repeated this over time and, ultimately, what they have now, going out 50 generations, are tame foxes that act and even look in some ways like pet dogs.”
The tame silver foxes love human interaction from attention to belly rubs, and exhibit traits like tail wagging, gazing into the faces of humans and a change in their barks. Physical changes accompanied these behavioral changes, with coat color shifting from silvered-black fur to a more mottled, piebald pattern, and tails becoming curly despite these traits not being intentional selected for by breeders. In contrast, those bred for aggression showed hyper aggressive responses to humans, as indicated by lunging at the cage.
The taming of the brain
A change in behavior as observed in these silver foxes likely comes with unseen shifts in genetics and brain function. Rosenfeld decided to look at these changes in the hypothalamus region of the brain with the help of researchers from the University of Illinois at Urbana-Champaign, Cornell University, the Broad Institute of MIT and Harvard and the Institute of Cytology and Genetics in Novosibirsk, Russia.
“We are interested in changes in gene expression associated with the hypothalamic-pituitary-adrenal axis, the main hormonal system involved in stress-response and it was very exciting and productive to collaborate with Dr. Rosenfeld and her colleagues on the analysis of gene expression in the hypothalamus of tame and aggressive foxes” said Anna Kukekova, the senior author and associate professor in the Department of Animal Sciences at the University of Illinois at Urbana-Champaign.
Rosenfeld compared genes in the hypothalamus between tame foxes and aggressive foxes as well as comparing them to genes in two other brain regions — the prefrontal cortex and the basal forebrain — significant in terms of learning and memory.
“The hypothalamus was a good target organ, because it controls social behaviors like getting along or gregariousness and usually hormones like the pro-social hormone oxytocin tends to increase in animals who are social,” Rosenfeld said. “We basically did a global approach, looking at every gene we could identify and how they differ in terms of expression between the tame and aggressive foxes.”
Among genes with differential hypothalamic expression in tame and aggressive foxes they found seven identical genes with the same pattern of expression between all three brain regions. It suggests that when you select for tameness that some genes will change regardless of brain region.
“It was interesting to us because these genes were involved in processes including cell division and making more neurons, differentiation, adhesion like how the cells contact each other, and the most surprising, carbohydrate processing.”
Rosenfeld commented that some of these involved — such as, carbohydrate processing — suggest potential changes to accommodate domestication between the tame and aggressive foxes. This falls in line with how scientists believe dogs became domesticated 10,000 years ago, growing ever closer to human populations and developing to scavenge their scraps and garbage, although in this study both tame and aggressive foxes were maintained on the same diet.
“As animals get domesticated, they have to also accommodate different diets than what they’ve been eating in the wild because now they’re getting scraps from humans,” Rosenfeld said. “They’re selecting for genes that are involved in carbohydrate process, like metabolism processing, so it’s sort of telling us when you consider domestication that we might have to think about how the animal may have to then turn on a whole set of other genes to accommodate this new diet.”
But there were other brain differences as well.
“We also found genes suppressed in tame foxes associated in inflammation processes we call interleukin signaling, cytokines production and communication between cells to each other, and this gene expression linked to whether they were tame versus aggressive.”
The researchers’ original idea that genes related to hormones like oxytocin ended up not panning out when they saw little change between tame and aggressive foxes. But, she said it was interesting that the prevalent changes they did see involved more genes down-regulated or suppressed in tame than aggressive foxes.
“Most of the genes in the hypothalamus actually we found were suppressed in tame relative to hyper aggressive foxes, you know, squashing a hyperactive response, Rosenfeld said. “So, it’s an interesting question to consider that, as dogs became more domesticated, did they become more prone to disease because they don’t have such a heightened immune response? We can’t really answer that question just yet.”
Kristal Gant is a long way from the student she was when she donned a lab coat and wielded a pipette in labs at Bond Life Sciences Center nearly four years ago.
As she stood in front of a group of MU students hoping to one day follow their own routes to graduate school, Gant recounted her long and winding path to her Ph.D. program at University of Wisconsin-Madison and how MU’s Post-Baccalaureate Research Education Program (PREP) Scholars helped her get there.
“I’m really passionate about wanting to give back and be kind of like a mentor, but also a motivational, navigational tool for these students,” Gant said. “In undergrad, I didn’t have any idea about research and I feel like it’s my duty to come back and talk about my experience. Most of these students have not seen people that look like them in graduate school, as Ph.D. candidates or doctors. They don’t even know that’s possible for themselves.”
Gant didn’t attend Mizzou for her undergraduate degree, but as a PREP Scholar here she gained the chance to hone her skills. It gives underrepresented groups opportunities for individual academic and professional development that range from mentoring and GRE preparation to mini courses and research experience. The end goal is to prepare them for applying to Ph.D. programs. Those in PREP spend one or two years refining their skills and knowledge.
Gant greatly expanded her experience in research during that time. She spent a year alternating between the labs of Cheryl Rosenfeld and Mike Roberts in Bond LSC, learning the ins and outs of research on reproduction and environmental chemicals like bisphenol A (BPA).
“It gave me a preview of what you go through in your first year of grad school. I knew I wanted to study reproduction, reproductive deficiency and disease, and was also interested in environmental and reproductive toxicology, initially,” Gant said. “When I came here, I had the best of both worlds; I had the BPA aspect with Dr. Rosenfeld looking at mouse models and how that affected their behaviors and I had the reproduction area where Dr. Roberts looks at placental development by converting embryonic stem cells to trophoblasts, the main cells responsible for placental function. The project was essentially perfect in accommodating both of my interests.”
Gant had a unique, sometimes turbulent path to her interest in science. She grew up and went to school on the Westbank of New Orleans, until ninth grade. She remembers first getting an interest in science in junior high when her teacher showed a time-lapse video about pregnancy and the development of a baby.
“I was really interested in like how the woman’s body knew to accommodate the baby and how it adapted to having another human inside of it. That really intrigued me, so I was like, ‘I want to do reproduction,’” Gant said. “That combined with “The Cosby Show” made me want to be a neonatal nurse or obstetrician. I pursued that initially, but then I was like, oh, whoa, I didn’t know you could actually research these things, and I was introduced to research careers and grad school in college and realized this could be a thing. So, yeah, I’m a nerd like that.”
Before she got there, life got a little derailed. When Hurricane Katrina hit, the 15-year-old girl got separated from her mother who was visiting her sister in Virginia, causing her to have to relocate to Texas with a family friend to avoid the storm. What started out as a few days of inconvenience quickly turned into a bigger situation.
“We saw on the news that there was extensive flooding and people were stuck on the roads, and our apartment was flooded out, so we lost everything,” Gant said. “My mom didn’t know if I had made it out or anything because the phone lines were down and we were separated two weeks before the family I was staying with in Texas flew me to Virginia where I ended up finishing high school.”
Gant completed a year of college at Virginia Commonwealth University before she moved to North Carolina to help her mother escape a domestic violence situation. They were left living in a shelter for abused women and children for a year before getting their own apartment, and Gant worked at McDonalds until she started college again at Elizabeth City State University. She graduated in 2014 and followed up with a couple internships before ending up in a customer service job.
“And I hated it because it was, like, I have a whole degree that I’m doing nothing with and I’m in debt from it and I need to do something with,” she said.
A former adviser recommended Gant apply for PREP Scholars to improve her chances of getting into grad school.
Gant said her struggles helped her figure out what she wanted to do and shaped how she saw her future. Understanding it also aided her in writing personal statements for graduate school applications. She related that insight to those current PREP students looking to her for advice.
“It requires a lot of self-reflection to understand how your struggle got you to where you are. It doesn’t have to be family or a natural disaster or relationship troubles or whatever. It could be something within you that you yourself struggle with internally, whether it be confidence or fear or a feeling of not being good enough to do something,” Gant said. “It could be something so small that you struggled with, overcame and still, you pursued something you were deathly afraid to do. That shows that no matter what is supposed to stop you, you’re not gonna allow it.”
But her parting advice was some of the best.
“It really takes a passion, knowing what you’re trying to answer and putting in the work to figure it out. If you’re not passionate then you will be miserable and feel like you’re trapped in a prison,” she said. “But if you want the answers to your research questions and will not rest until you figure it out, then you should be in graduate school.”
Kristal Gant is a fourth-year Ph.D. candidate at the University of Wisconsin-Madison studying Endocrinology and Reproductive Physiology in the Department of Obstetrics and Gynecology. She was an MU PREP Scholar in 2015 and plans to graduate with her doctorate in 2021.
Saurav Sarma grew up amongst tea plantations and medicinal plants in the northeastern corner of India near Tibet, a state called Assam.
His day-to-day observations of the plants sparked a curiosity that eventually led him to a career looking at the chemical building blocks behind it all in the labs of Lloyd Sumner and the University of Missouri Metabolomics Center at Bond Life Sciences Center.
His interest revolved around the connections between carbon, oxygen, nitrogen and hydrogen, which make up living systems.
“How they’re connected makes all the difference,” he said.
Sarma enjoys working in the metabolomics core because of the incredible facilities and collaboration. Among other things, his job is to look for thousands of molecules to find biomarkers for various diseases.
“The purpose of the core is to profile the small molecules,” he said. “So, for example, a group might want to see the molecular differences between a healthy plant and a diseased one. There are thousands of molecules, so you need sophisticated techniques to profile those molecules because they are otherwise unknown.”
Sarma works with people on and off campus who are curious about the molecules in their areas of research, but he also does data analysis, communication and collaborative research project. He enjoys the diversity of his job, which is focused on how molecules shape our lives.
“Finding something new is always exciting,” he said. “Science can always surprise you.”
While he finds this research to be fascinating, he also enjoys how it can help people and push civilization forward. From health to the economy to agriculture, he said science benefits us in ways we often don’t realize or think about.
“So, it’s not that my work is great, it’s that everybody’s work is great,” he said. “Everything that we use nowadays didn’t come up in one day, it’s from people’s hard work over many years, and maybe someone will benefit from our work in the future.”
Things may not always go as planned, but he doesn’t let that stop him.
“In science, nothing is a failure,” he said. “The knowledge you are generating today is helping researchers in the future, so learning how to deal with failure and keeping an open-mind is important.”
He said that it’s easy to get stuck in mental patterns, and by keeping an open-mind, you’re more likely to see or think of things you might not otherwise see in your own research, in conversations and daily life, too. Many of the most important discoveries of humanity occurred outside of the normal paradigm. And while ‘failure’ can be challenging and frustrating, he said it makes the success more significant.
“As a synthetic chemist, I run a hundred reactions and maybe 10 work and 90 fail,” he said. “So, it helps you to deal with failures, but it also feels great when you reach a goal. You are getting through hurdles and it gives you this satisfaction of getting something done that wasn’t easy to get done.”
He received his undergraduate degree in science, followed by a masters in organic chemistry before making the journey to North Carolina for his Ph.D. in medicinal organic chemistry. After his Ph.D., he arrived at MU in the radiology department for his postdoc. While there, he developed a trimodal drug delivery system called closomer to help minimize the side effects of cancer.
“I was fascinated by working with drug delivery systems, but then again, it was about molecules and their characterization and identification,” he said. “That’s been a binding thing throughout all of my research.”
Apart from science, he loves the classics – literature, music, sports and movies. He’s currently reading “Thousand Splendid Suns.” He also loves hanging out with his four-year-old daughter watching cartoons. “I don’t have any exceptional hobbies,” he said.
A personal career goal of his is to develop sophisticated methods for exploring more of the chemical space that is still unknown, and he hopes to see a greater breakthrough for cancer treatment in his lifetime that allows for less pain and side effects.
Dry erase markers and Styrofoam molecular models are a part of Amanda Paz Herrera’s repertoire when teaching complex scientific processes to the average person.
Teaching the next generation of scientists requires work and discipline, but Paz Herrera is up for the task.
Paz Herrera takes her science on the road with Science on Wheels, a traveling group of graduate students and postdoctoral researchers at MU who aim to make science accessible to rural communities in Columbia’s surrounding counties. Sciences on Wheels visits schools, nursing homes, clubs and public events making it imperative to communicate complex scientific processes and mechanisms to all learning levels.
“We should be able to build a knowledge bridge to communicate what we as scientists do without jargon making people feel uncomfortable,” said Paz Herrera, a third-year biochemistry Ph.D. student in Donald Burke’s lab at Bond LSC. “We’re supported by taxpayer money, so the community has a right to know how that money is being used and how we’re moving forward scientifically.”
Paz Herrera emphasizes the importance of diversity and representation in the field on top of her passion for science education and outreach.
“Scientists look like you and me and there’s way more diversity than is depicted in popular thought,” Paz Herrera said. “One of the reasons I do science on wheels is to show what a scientist can look like and that brings a lot of power to little kids that may look like me. When they see someone that looks like them that can do this, that is life-changing.”
Paz Herrera’s research has been driven by her desire to see and understand things at the tiniest level. When she was in the second grade, she owned a play light microscope and would look at her hair or the fibers from her shirt.
When going through the three rotations at the start of her doctorate program, Paz Herrera visited a nuclear magnetic resonance lab and an X-ray crystallography lab, both of which would provide her expertise in studying biology at the structural level. However, her third rotation in the Burke lab changed her perception of what the rest of her program could look like.
While the Burke lab doesn’t specialize in structural biology, its focus on viruses and cancers offers an avenue for Paz Herrera to apply her interest.
A recent study Paz Herrera collaborated on with her colleagues from the Burke lab and researchers across campus optimized RNA and DNA molecules, called aptamers, to carry cancer diagnostics or therapeutics like backpacks to receptors on cell surfaces.
Now, Paz Herrera is looking to visualize the interaction of those same molecules with a protein on the cell surface of the Ebola virus for her dissertation.
However, working with the actual Ebola virus requires a biosafety level 4, and the Bond Life Sciences Center only has a biosafety level 2. So, the researchers in the Burke lab had to get creative.
To study the virus interaction in a safe manner, collaborative researcher Alex Bukreyev who works in Galveston, Texas, engineered a lab model that combines a cattle virus with the protein present on the Ebola virus cells. Because the virus only infects cattle, researchers won’t be infected but can still study what they’re most interested in – the glycoprotein on Ebola cells.
Paz Herrera wants to visualize the interaction to understand how that happens. Understanding the interaction between the proteins on the surface of cells and the aptamers can help researchers develop drugs or diagnostics further down the line.
Visualizing it isn’t as easy as looking under a microscope. By themselves, aptamers can’t be seen on the surface of a cell, making it impossible to find where they are or see how they are functioning.
Paz Herrera is working on building a ‘plug-and-play’ modular dart made up of an aptamer, an interjecting body and a gold nanoparticle tail. The gold nanoparticle tail allows her to see where the aptamer is and subsequently visualize the interaction happening.
Using a basic electron microscope available in Mizzou’s Electron Microscope Core, Paz Herrera has begun to infer where the interaction is using staining. However, she is looking forward to using cryo-electron microscopy (CryoEM) that will soon be available. Using CryoEM will allow her to see the aptamer interaction embedded in ice, providing more molecular detail.
The interjecting body in her model joins the gold nanoparticle with a compatible aptamer. This technology can expand far past Ebola and will help researchers study the interaction between aptamers and proteins in other applications.
Paz Herrera didn’t have much research experience as an undergrad. Instead, she did a lot of educational outreach with elementary and high school students.
“I would do cheek cell samples with them. They would swab the inside of their cheek, put it on a slide and stain it and see their own cells,” Paz Herrera said. “They would go crazy.”
As she progressed in her biochemistry career, she learned that there was more to science than viewing cells under a microscope. She saw graduate school as an opportunity to solidify herself as a scientist and also to prepare to teach the next generation of scientists.
“I really want to do what some of the best professors did for me – to inspire a thirst for inquiry and asking questions,” Paz Herrera said. “When a professor uses an acronym in class, they expect you to understand what they’re saying, but learning isn’t like that and shouldn’t be like that. Sometimes we have great experts in the field that have the curse of knowledge and don’t have the best tools to communicate that knowledge.”
Paz Herrera is also minoring in college teaching and has been shadowing Margaret Lange’s classes, an assistant professor in the Department of Molecular Microbiology and Immunology, to prepare herself as a future educator. She also has the ambitious goal of being a guest lecturer in all of the biochemistry undergraduate classes to strengthen her skills and receive feedback.
Her goal is to make learning science more relatable and enjoyable.
“As I progress in my education, although I become focused in my field, I will never forget where I started so that when I teach, I can break the complexity barrier,” Paz Herrera said. “I want to make science appealing, understandable and accessible not only to my future students but to the community and public as well.”
Missouri Life Sciences Week 2019 has come to a close. It brought us a taste of science across our broad research community at Mizzou. From students presenting their hard work in labs to core facilities showing what they do to advance the work of scientists across campus, Bond LSC was bustling with energy.
If you missed the action, get a taste of what it all in the photos from the week’s events below or our daily recap email links below.
But first, here’s a list of winners from the research poster session contests. It’s a challenge to pick the best research presentations from a field of nearly 300 posters. With the help of a small army of volunteer faculty and postdoctoral students, organizers narrowed the field to 39 undergrad and graduate students who skillfully explained quality science created through their research.
Social & Behavioral Sciences 1st: Hadeel AlQadi “An Overview of Cognitive Diagnosis Model for Dichotomous Latent Variables.”
Adviser: Sangbeak Ye2nd (tie): Kelsey Irvin “Sensitivity of the Reward Positivity Event-Related Potential to a Savoring Affect Regulation Strategy.”
Adviser: Debora Bell2nd (tie): Kolter Grigsby “The Role of Nucleus Accumbens CREB and PKIÎ± modulation in Rescuing Low Voluntary Running Behavior.”
Adviser: Frank BoothLife Sciences Innovations
1st: Faye McGechie “Using Novel 3D Techniques to Visualize and Quantify Primate Neck Anatomy.”
Adviser: Carol Ward
2nd (tie): Aditi Mishra “Generation Of Novel Thermogenetic Tools In Drosophila Melanogaster.”
Adviser: Troy Zars
2nd (tie): Li Lee “T2-mapping Magnetic Resonance Imaging As A Novel Strategy To Detect And Quantify Myocardial Fibrosis In Mice”
Adviser: lixin Ma
Honorable Mention: Chunye Zhang “The Influence Of Gm Richness And Transfer Method On Disease Susceptibility In An Animal Model.”
Adviser: Aaron C. Ericsson
Honorable Mention: Paige Gruenke “2′-Fluoro-Pyrimidine-Modified RNAs Strongly Inhibit HIV Reverse Transcriptase.”
Adviser: Donald Burke-Agüero
Animal Biology, Health and Disease 1st: Karl Kerns “Sperm Capacitation-induced Zinc Efflux is Necessary for Increased Proteasomal Activity and Release from Oviduct Glycans of the Sperm Reservoir.”
Adviser: Peter Sutovsky
2nd: Alexis Dadelahi “B Cells Inhibit CD4-mediated Protection During Brucella Melitensis Infection via an MHCII-dependent Mechanism.”
Adviser: Jerod Skyberg
3rd (tie): Emma Stephenson “Effects of Copper, Zinc, and Manganese Source and Concentration during Late Gestation on Fetal Growth and Mineral Status of Calves.”
Adviser: Allison Meyer
3rd (tie): Monica Witzke “Experimental Heat Stress Alters the Fecal Microbiome of Dairy Cattle.”
Adviser: Pamela Adkins
Honorable Mention: David Korasick “Investigating the Dynamic and Complex Oligomeric States of Aldehyde Dehydrogenase 7A1.”
Adviser: Jack Tanner
Honorable Mention: Kinjal Majumder “Parvovirus Minute Virus of Mice Interacts with Sites of Cellular DNA Damage to Establish and Amplify its Lytic Infection.”
Adviser: David Pintel
Plant Biology, Health and Disease 1st: Jan Lorie Robil
“The Role of Auxin in Vein Patterning in Maize Leaves.”
Adviser: Paula McSteen
2nd: Jared Ellingsen “Establishing the Roles and Interactions of E3L1 and MKP1 in Pattern-triggered Immunity.”
Adviser: Scott Peck
3rd: Caio Canella Vieira “Major Gene for Resistance to Root-knot Nematode Sustains Yield Response Under High Nematode Pressure.”
Adviser: Pengyin Chen
Comparative and Translational Medicine
1st: Kari Chesney “Modeling Crohn’s Disease: Identifying Environmental Triggers in a Genetically Susceptible Atg16l1 Rat Strain.”
Adviser: Elizabeth Bryda
2nd: Robert Kazmierczak “Targeting Neuroendocrine Prostate Cancer.”
Adviser: Chiswili Chabu
3rd: Lindsey Ledbetter “Eosinophils Are Important for Early Formalin-inactivated Coxiella Burnetii Phase I Vaccine-mediated Protection and Antibody Isotype Switching.”
Adviser: Guoquan Zhang
Honorable Mention: Catherine Chambers “IL-1 is Protective in a Murine Model of Neonatal Meningitis-Associated E. coli Infection.”
Adviser: Jerod Skyberg
Honorable Mention: Hien Huynh “Antigen Requirements to Achieve T Cell Co-potentiation When Targeting Human CD3 with Fab Fragments in Humanized Mouse Models Expressing Transgenic TCRs.”
Adviser: Diana Gil Pages
Honorable Mention: Sessaly Reich “HER2 Antibody Validation in Dogs and Expression Pattern in Canine Osteosarcoma Cell Lines and Tissues.”
Adviser: Jeffrey Bryan
Ecological and Evolutionary Biology
1st: Makenzie Mabry “Brassica oleracea: The Dog of the Plant World.”
Adviser: J. Chris Pires
2nd: Troy Rowan “Detecting Signatures of Selection and Local Adaptation in United States Bos Taurus Beef Cattle.”
Adviser: Jared Decker
3rd: Erin Petty “Which Resources Control Algal Biomass in Turbid Missouri Reservoirs: Light or Nutrients?”
Adviser: Rebecca North
Honorable Mention: Micah Turrell “Evaluating the Critical Thermal Maxima Among Four Species of Missouri Salamanders.”
Adviser: Manuel Leal
Bioinformatics and Computational Biology
1st (tie): Sadia Akter “A Machine Learning Approach for the Prediction of Endometriosis Using Multi-OMICS Next Generation Sequencing Data.”
Adviser: Trupti Joshi
1st (tie): Nicholas Mattia Marazzi “Quantitative Evidence of the Role of the Lymphatic System in Maintaining the Subatmospheric Pressure Condition in the Interstitial Space.”
Adviser: Giovanna Guidoboni
3rd: Adil Al-Azzawi “Super Clustering Approach for Fully Automated Single Particle Picking in Cryo-EM.”
Adviser: Jianlin Cheng
1st: Olivia Botonis “Distinct Roles of Two Dopaminergic Pathways in Reinforcement Learning.”
Adviser: Ilker Ozden
1st: Andrew Yowell “An Essential Endopeptidase is Required for Cell Wall Synthesis and Morphology in A. tumefaciens.”
Adviser: Pamela Brown
2nd: Maha Hamed “Role of Salicylic Acid in Immune Responses in Arabidopsis Clathrin-Coated Vesicle Mutants.”
Adviser: Antje Heese
2nd: Alec Wilken “Functional Morphology of the Palate in Varanus exanthematicus and Its Significance for the Evolution of Cranial Kinesis.”
Adviser: Casey Holliday
3rd: Mason Ward “Say Yes to the Host: The Effects of Drought on Parasitoid Wasp Behavior.”
Adviser: Debbie Finke
Honorable Mention: Aleks Shin “Quantitative Analysis of Glycated Albumin by LC-MS/MS Using an Isotopically Labelled Standard.”
Adviser: Kuanysh Kabytaev
Honorable Mention: Skyler Kramer “Novel Improvements on a Machine Learning-based Approach for Large-scale Prediction of Negative-mode Collisional Cross Sections.” Adviser: Lloyd Sumner
Honorable Mention: Kody Jones “Uncoupling Functions of Dynamin-related Protein Network in Plant Immune Responses from Development.”
Adviser: Antje Heese
Lead Organizer for Each Category
Social & Behavioral Sciences, Nate Green
Life Science Innovations, Mike Lewis
Animal Biology, Health and Disease, Jim Amos-Langraf
Plant Biology, Health and Disease, Scott Peck
Comparative and Translational Medicine, Jeff Bryan
Ecological and Evolutionary Biology, Rex Cocroft
Bioinformatics and Computational Biology, Chi-Ren Shyu
Undergraduates: D Cornelison
With eyes wide open, glued to metal tubes, researchers from across the University of Missouri’s campus are searching for answers that are unseeable to the unequipped human eye.
The Advanced Light Microscopy Core is a resource for anyone to come and further understand their research. The Core’s Imaging Specialist, Frank Baker, has been an intermediary between the facilities equipment and researchers for four years.
Molecular cytology is the localization of molecules within the cell. In other words, researchers look at molecular methods occurring to understand cellular functions. The core has a number of resources such as confocal, super-resolution and digital light-sheet microscopes.
Though microscopes are normally thought of as a scope to look directly into, new technology is available that can create 3D images on a monitor of the cells.
“One thing I like about working here is it gives me a perspective about the diversity of work being done at the university,” Baker said.
For Baker, one of the greatest parts about MU is its interdisciplinary nature. Any researcher from any department can bring their goals and their problems to the MCC and search for answers, and Baker gets to be a part of that journey.
“And sometimes when the problem is especially confounding, and you have all of these pieces that don’t make sense, you have that mental flash when everything integrates together into an answer. It’s a really beautiful moment,” Baker said.
Baker began his science journey here at MU where he received his undergraduate degree. He then moved on to Berkley to study plant developmental genetics and then did his postdoc at Pennsylvania State.
“I’ve always liked microscopy quite a bit, even in my undergrad days,” Baker said. “I thought, I really do like doing this, and so I decided to make a transfer.”
Baker has been in the MCC for four years now and said he is content for the moment.
“It’s always interesting because people come with new problems and new types of experiments, and so with the job, there is always a goal to keep learning,” Baker said.
On the horizon, Baker can see a future where he directs his own core. He said it’s important to him that it stays fairly broad to serve multiple purposes, similar to the MCC. Baker believes in setting goals and collaborating with others to reach them.
“I enjoy this job for a number of reasons. I like the diversity of work being done here… it does provide a sense of mission. Because the work that is being done here is critical to a lot of work being done at the university,” Baker said. “I enjoy that sense of working to achieve both the universities goal to support researchers and also to see work happen that has a positive effect.”
While goals can vary is size and scope, Baker makes it a priority to see both the small and big picture. When he can’t understand something about his research, he finds it useful to step back and take a look at the larger community, or to look at previous work being done on the topic. He values the complexity of science and how a change in perspective can be a shift in understanding.
“What I love about science is looking into the unknown, not knowing what the answer is, devising a hypothesis based on what you do know, and then doing the experiments to find out what the answer is,” Baker said.