Clement Essien poses outside Bond LSC near the building’s garden. | photo by Lauren Hines, Bond LSC.
By Lauren Hines | Bond LSC
Artificial intelligence (AI) can do more than just write a book given a few words. It can help make cancer treatments more effective and predict the presence of disease in cells, which doctoral student Clement Essien did through his recent project.
“It’s exciting because for several years, I was a software engineer, and then I felt like I wanted to do something more with that,” Essien said. “I want to make some contribution to understanding disease and also in the diagnosis and treatment of diseases. So, I had to look for ways that I could apply computing to understand and possibly solve many biological problems.”
Essien — who works with Bond LSC principal investigator Dong Xu — is trying to predict the binding sites of metal-binding proteins called metalloproteins using AI technology, specifically deep learning.
“Metal binding can play a very functional role,” said Dong Xu, Shumaker Endowed Professor in Bioinformatics, Director of Information Technology Program. “That is why it’s important to know whether a protein binds to a particular metal, and also if you really could, you’d want more details on where it binds.”
Even though Essien’s work is still underway, it has big implications.
“[My work] helps to advance the research geared towards improving the prediction capability of machine learning modules that work on this problem and also provide an important step towards understanding protein functions, and their implications for gene product characterization, drug design for certain diseases and enzyme engineering.
Not only could predicting the binding sites of metal proteins help create drug targets and advance other research, but it could also possibly help identify the presence of disease.
By predicting the binding site, researchers can figure out the protein’s structure and therefore infer the function.
“[The function is] what tells you what role the protein plays in the body,” Essien said. “Also, the presence or absence or mutation of a particular protein sequence can cause diseases.”
Essien’s previous project had the same goal of predicting zinc binding sites, but now he is expanding his research to the study of many other metals found in the human body. Essien is also using an AI technique called Natural Language Processing (NLP).
One use for NLP would be to give an AI all the words in the dictionary and then ask it to write a book. In Essien’s work, he is trying to model the protein sequences as a text because they consist of a sequence of letters, and then get the AI to learn representations from it.
“So, we are trying to model the problem as a natural language problem in the sense that those series of letters you see in the protein sequences, they may be represented as words,” Essien said. “So, if you’re able to break that code you might be able to learn some important things.”
Essien published one paper in a conference and expects to have another one out in a few months. Although, he has much more to discover until then.
“It’s one thing to see I’m able to predict these to a certain accuracy, but it’s also important to learn what is going on inside,” Essien said. “Is there any new significance to learn?”
Jiude Mao works on BPA testing in the lab of Cheryl Rosenfeld.
By Mariah Cox | Bond LSC
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.
Mizzou was always near the top of Olivia Warner’s list for Ph.D. programs.
Its renowned psychological sciences program, sound training in Warner’s specialty of addiction and supportive, collaborative atmosphere that she didn’t see at other places made it a top choice on paper.
But she was not introduced to her most formative program in terms of professional development until she had already moved across the country from Arizona to mid-Missouri. Within her first month, Warner learned of the Maximizing Access to Research Careers/Initiative for Maximizing Student Diversity (MARC/IMSD) program.
“I found out about IMSD right away, and I’m glad I did,” Warner said. “Without this program, I would have had a tougher time networking on campus, and wouldn’t have picked up a lot of the skills that I have today.”
MARC/IMSD is a federal program that partners with universities to identify and train the next generation of researchers in biomedical and behavioral sciences. It provides research, mentoring, academic and social support, and professional development to help them along the way to doctoral degrees that will lead them to diversify the workforce. These underserved students include minorities from different ethnic and racial backgrounds, those with disabilities, students from low socioeconomic backgrounds and first-generation college students. The program gives them a helping hand in graduate school.
“Evidence says teams from diverse backgrounds approach problems differently and, ultimately, better in terms of solutions than teams of individuals from similar backgrounds,” said Dr. Mark Hannink, director of MARC/IMSD, Bond Life Sciences Center principal investigator and Biochemistry faculty member. “Data drives the National Institutes of Health’s recognition that entire research enterprises benefit from different perspectives and approaches.”
For 20 years, Mizzou was the recipient of an MARC/IMSD grant from the National Institutes of Health (NIH), that provided mentored research training and professional development to both undergraduate and graduate students. Hannink said that while the mentoring and professional development will continue, there will be changes in MARC/IMSD’s structure with the new grant. The most significant change is that the undergraduate and graduate training programs are now separated into two different grant-funded programs. The graduate MARC/IMSD program, which will become a T32 training program, has recently received $2.2M in funding from NIH to support training of 25 students over five years. A number of units at MU, including the School of Medicine, College of Veterinary Medicine, College of Engineering, College of Food, Agriculture and Natural Resources, the Division of Biological Sciences and the Graduate School, have provided funding to support training of at least 10 additional students. The MARC/IMSD program is truly a partnership between NIH and MU that will have a significant impact on diversity in biomedical research.
“This is more than just a scholarship,” Hannink said. “It’s a training program, in which students develop three different areas of expertise that our students need to develop to become successful scientists: professional, technical and operational skills.”
These objectives include increasing the percentage of underrepresented minorities in participating biomedical predoctoral students to 20% from 16%, to improve the Ph.D. completion rate for such students to 90% from its current 84%. An end goal is that 30% of trainees obtain external fellowships during their time in the program.
While MARC/IMSD provides two years of financial support to participants, its key focus is to foster professional development programs, workshops and support mechanisms to ensure that students in the program have whatever they need to succeed.
Coming out of Arizona State University with degrees in Psychology and Human Development, Warner worked full time for three years and volunteered in a lab, researching the ways in which contextual and interpersonal factors influence alcohol use motives and subsequent problematic use.
Despite significant research experience, Warner’s transition into the six-year clinical psych sciences Ph.D. program would have been much more difficult if not for MARC/IMSD.
“I was connected with Dr. Hannink pretty much immediately after I arrived on campus, and surrounded with people in the program that had a lot of shared experiences with me,” she said. “The program provided extra support and a sense of togetherness for us, which is really important since a lot of us are underrepresented in Ph.D. programs. It really helps to be around a group of people you can relate to and connect with.”
Under the new grant, much of the mentoring aspect of the program will remain the same, but the new format will be much more explicit in terms of the specific training activities used to develop said technical, operational and professional skills.
In addition to moral support and togetherness, MARC/IMSD aims to equip participants with academic skills. For Warner, who just completed her second year of the program, this meant taking a professional development class taught by Hannink. The class included a segment on public speaking which was especially beneficial for Warner.
“Having public speaking and presentation skills is a large part of any successful researcher’s skill set, so it was really helpful for me to be able to develop those skills early on in the program,” Warner said.
Participants also complete rotations in other labs besides their own as part of the program in order to broaden their knowledge about all areas of research, and are given opportunities to network with experts in the field. Many cycle through labs within Bond LSC.
“The next generation of researchers need to have exposure to disciplines outside their degree, to be able to talk with people doing research that’s very different than their own and collaborate effectively,” Hannink said.
Warner wants to be able to continue her research in some capacity for the rest of her career, so being a well-rounded graduate able to face any challenges thrown at her is invaluable.
“Everything I’ve been a part of in this program, from the professional development class, to being exposed to areas of research I might not have otherwise known anything about, has been very beneficial,” she said.
The science community as a whole reaps benefits from this development.
“Any research effort is more effective if it’s inclusive and brings different perspectives and approaches to the problem, and that’s how the skills IMSD teaches really translate long term into a better biomedical workforce.”
MU received a National Institutes of Health five-year grant for $2,228,008 to continue its focus on minority graduate student development in biomedical and behavioral sciences. This grant started February 1, 2020.
The structure and placement of labs encourages researchers to collaborate and talk to each other and often, connections and friendships are formed.
For Kinjal Majumder, a virologist and postdoctoral fellow in the David Pintel lab at Bond Life Sciences Center, that has meant bouncing many ideas off friends and colleagues from neighboring labs. Little did he know that one connection would lead him to interesting findings in a field outside of virology.
Those results may help make progress toward understanding the machinery behind drug resistance and toxicity in the body.
“The big picture is that it will help future studies on how drugs are metabolized by our body,” Majumder said.
The connection started with Andrew Huber, the first author of the paper, who completed his Ph.D. while in the lab of Dr. Stefan Sarafianos at Bond LSC. He graduated two years ago, moved to the lab of Dr. Taosheng Chen at St. Jude Children’s Research Hospital (SJCRH) in Memphis, Tenn. and began his postdoctoral work.
Dr. Chen’s lab focuses on mechanisms of cellular drug metabolism, one of which functions through the pregnane X receptor (PXR) protein.
PXR is found in the liver and is activated by drugs and other substances in the blood. Once activated, it binds to DNA and activates genes responsible for detoxifying the system. However, this system often leads to metabolism and reduced efficacy of administered drugs such as chemotherapies and antibiotics.
“When Andrew was in the Sarafianos lab, we’d talk science often and we collaborated on how different viral proteins bind to host and virus DNA, and how this can aid viral life cycles,” Majumder said, “When he moved on to his postdoctoral work, he saw that he can start applying similar techniques to study how the liver metabolizes toxins. So that’s when we set up this collaboration to pursue these things together.”
Majumder studies how viral DNA and proteins interact in virus-infected cells. One technique he uses is called chromatin immunoprecipitation assay (ChIP) which determines where proteins of interest can bind to DNA molecules. Majumder freezes protein and DNA that are interacting together in the process and he pulls that complex down with an antibody. “It’s like going fishing,” he said.
In order to apply ChIP and other techniques to study PXR signaling, Majumder drove down to SJCRH in Memphis to work with Huber on these assays.
Once in Memphis, Majumder and his collaborators worked and conducted experiments around the clock, but they also found time to explore the city and have fun.
“We go into lab and try to get done as many experiments as we can,” Majumder said, “And whenever we have a long break we go out on the town. It’s usually a really fun way to go and experience the life and scientific culture of a new place.”
It is a lot to pack into one week, but Majumder and his collaborators make the most of it, finding a way to effectively balance their studies on PXR with soaking up life in Memphis.
Majumder compares PXR to a light dimmer switch. When activated, it “brightens” by increasing drug metabolism, leading to decreased drug efficacy. PXR inhibitors work to “dim” this effect. At St. Jude, Dr. Chen’s group found that of the 434 amino acids that make up PXR, only one mutation is needed to “turn a dimmer into a brightener.”
“We sort of got lucky, we thought that you’d have to make a lot of changes in order to make PXR do something different,” Majumder said, “Without making too many changes — Dr. Chen’s group just switched one thing — and that was sufficient enough to turn it into a brightener. So that was a happy and unexpected outcome.”
Once these results were reviewed, the Cellular and Molecular Life Sciences journal accepted their results and published them this March in an article titled “Mutation of a single amino acid of pregnane X receptor switches an antagonist to agonist by altering AF-2 helix positioning.”
Looking ahead, Majumder and his collaborators hope to make more progress in understanding how drugs are metabolized in the body.
All of this would not have been possible if it wasn’t for the connections Majumder made at Bond LSC a few years ago.
“It was so cool to have this opportunity to collaborate with someone from the LSC that I have collaborated with before and apply our experimental techniques to study a new system,” Majumder said, “It feels very encouraging that now the work can be expanded upon and applied to other systems and settings.”
Landon Swartz, undergraduate student researcher, is motivated by a simple desire — to help others through the power of computer engineering.
Coming from Springfield, Missouri, Swartz decided to go to Mizzou in 2017.
“I chose engineering,” Swartz said. “It fits my idea of solving problems, but also lets me be able to see a benefit to people.”
Swartz got involved in research through the honors college after he talked to David Mendoza, associate professor in plant sciences and Bond LSC investigator. Mendoza was looking for people to help program and build his data collection machines.
“Robotics is right up my alley,” Swartz said.
In the Mendoza lab, Swartz was modeling the robot and programming it to move, take pictures and run diagnostics.
This experience eventually led Swartz to win the summer 2020 Cherng fellowship from the MU honors college. The nine-week research program provides networking and presentation events along with a $1,000 project expense account.
“It feels really great,” Swartz said. “It was really nice to be able to win that because you do have to plan a full project, like, the beginning, middle and end of everything. So, it’s nice to be able to not only plan that out, but to actually get to do it and get the funding and support to do it.”
The fellowship will help Swartz create his own idea for a robot. After seeing the potential of the robot that images root growth in Mendoza’s lab, Swartz wanted to expand it further by adding an automated hydroponic system.
The system will help researchers easily control variables that will affect the plant and watch how physical traits are affected.
“The reason I came up with the idea for hydroponics is because after watching my lab mates try to do hydroponics, it’s a very labor-intensive procedure,” Swartz said. “It’s a very error prone procedure because you have to do everything manually.”
In addition to saving time for researchers, the robot will also potentially help eliminate human bias in research and increase efficiency.
Since Swartz’ project straddles plant biology and engineering, funding can be hard to find.
“If you can’t find that enthusiasm from grants or any other place, you kind of have to figure it out along the way,” Swartz said. “So, this fellowship will help us a lot with kind of establishing more examples of how you can use automated phenotyping.”
When Swartz isn’t working in the lab or going to his computer engineering classes, he can be found practicing bass guitar, playing the trumpet or running the soundboard for a college ministry on campus.
“Whenever I get confronted with a problem, I usually go and practice for a while just because I feel like it opens up another side of my brain,” Swartz said.
Swartz has been playing the trumpet since middle school and the bass guitar since freshman year of college. Swartz sees the importance of his research even in music.
“Seeing where engineering intersects with plant biology and healthcare and going back to music, like audio equipment, things like that, there’s engineering and everything,” Swartz said.
Swartz sees the potential and power of computer engineering and how it can help people and researchers alike. He plans to be in the lab this summer to try and make that potential a reality.
“Knowing you’re going to be a piece in a puzzle to something greater…. that’s what keeps me going,” Swartz said.
Haval Shirwan and Esma Yolcu arrive at Bond LSC as accomplished researchers.
While having different expertise within the field of immunology, the married couple collaborates extensively on research and together developed ProtEx technology, an alternative to traditional methods of gene therapy for immunomodulation with applications to autoimmune diseases, transplantation, cancer immunoprevention and immunotherapy, and vaccines against infections
With work published in numerous peer-reviewed journals and 19 patents to Shirwan’s name, they both arrive at Mizzou ready to build on their research background and contribute to the new precision medicine focus for the UM System.
But success didn’t always come easily for the couple.
Shirwan grew up in the shadows of Mount Ararat in eastern Turkey, and was always fascinated by how the beautiful nature in the area came to life during spring after a harsh winter. From then, he knew he wanted to spend his life studying something in a science-related field.
After completing his undergraduate education in Turkey, Shirwan received a scholarship via NATO to complete his Ph.D. in the United States at UC-Santa Barbara. From there, he obtained a postdoctoral fellowship at California Institute of Technology, where he worked under an esteemed group of researchers, spent a few years in Philadelphia and arrived at the University of Louisville where he has spent over 20 years in the Department of Microbiology and Immunology.
Yolcu also grew up in Turkey, but did not meet the man who is now her husband until much later in life.
After completing her undergrad and Ph.D. in her homeland, she faced a difficult decision, between continuing in her field of training — cancer biology — or taking a leap of faith to pursue her emerging passion of immunology. That decision would require her to move to the United States for a fellowship at the University of Louisville, which she did. She originally planned to return to Turkey after the fellowship, but after meeting Shirwan, decided to settle in the US and make her career here.
Shirwan and Yolcu bonded over their passion for immunology worked together to develop their esteemed ProtEx technology. But, their initial desire to do so came not out of inspiration but rather out of frustration at the shortcomings of traditional gene therapy methods.
“DNA-based gene therapy is a complicated, exhaustive and expensive technology,” Shirwan said. “We wanted to see if there was a more efficient way to do immunomodulation.”
In traditional methods of gene therapy, DNA must first be introduced into the cell, but ProtEx technology bypasses that step, instead sticking the protein directly on the cell surface for immunotherapy.
The advantages of this method are twofold: it is much more efficient than gene therapy and allows proteins which may be harmful to the cell to “get out of the way” quicker once the process is completed.
Although this technology has received much acclaim from the global scientific community, the breakthroughs took years of work. While Shirwan took charge of the more technical details of ProtEx, it was Yolcu who urged him to be patient and keep trying new strategies when he was ready to give up on the technology altogether.
“In the mid 90s was when we had our breakthrough with ProtEx,” he said. “By the time we reached that point, I was about ready to give up, but (Yolcu) urged me to keep trying.”
Their breakthrough came when a group of animals treated with ProtEx techniques experienced unprecedented recession of cancerous tumors on their body. At first skeptical, Shirwan and Yolcu repeated the experiment several times. The result was the same; the control groups saw enlarged tumors while the group treated with ProtEx technology saw their tumors recede greatly. Their innovative immunomodulation technique of placing protein directly on the cell surface had worked. The couple published their ProtEx findings initially in 2002, but continued to fine-tune ProtEx and discover new things along the way.
While they have already accomplished so much together, they believe they still have much left to learn.
“What’s so fascinating about immunology is that we often think we’ve made so much progress and know so much about the immune system, but in reality, we still know very little,” Yolcu said. “Studying immunology gives me a sense of peace, and I’m excited to continue our work at Bond LSC.”
To that end, the couple aims to establish themselves at Mizzou as soon as it’s safe to do so (they are currently in the midst of a multi-phased moving process due to COVID-19).
This type of research contributes to the University of Missouri System’s NextGen Precision Health focus. The NextGen Initiative unites scientists, government and industry leaders with innovators from across the system’s four research universities in pursuit of life-changing precision health advancements.
Shirwan and Yolcu will establish a Center for Immunomodulation and Translational Research and aim to collaborate with clinical colleagues and scientists from all different backgrounds to continue to make headway in their work with the immune system.
“We want to build a powerhouse here,” Shirwan said.
Kwaku Tawiah, Ph.D. candidate, poses on the fifth floor of Bond LSC. | photo by Mariah Cox, Bond LSC.
By Lauren Hines | Bond LSC
Disease diagnosis takes money, time and technology — something rural communities don’t always possess. Kwaku Tawiah, a fifth-year graduate student, and researchers in the Burke lab are creating a probe that can diagnose and inhibit viral diseases cheaply, in less time and without electricity.
“With some of these infections, the faster you’re able to detect it, the better,” Tawiah said. “So, one of my motivations in grad school was to come up with some of these assays that don’t require all this time for experimentation.”
Some rural communities, like Tawiah’s hometown in Ghana, don’t have the electricity to operate diagnostic machines or the resources to afford them. The probe helps solve this problem.
The probe is a structure made up of a single strand of DNA that can fold into a unique 3D shape, which can recognize and bind to the surface protein of a virus.
“It’s a string of DNA, right?” Tawiah said. “What is unique about these probes is you can easily attach other things to the string of DNA.”
Tawiah and other researchers attach fluorescent molecules to the end of the DNA strand so when it binds to the surface protein, they can detect the virus.
Tawiah’s paper on the probe that can detect and inhibit Marburg, a cousin of the Ebola virus, will be submitted for peer review within a few weeks.
Even though Tawiah is graduating, other students in the lab want to expand the application of the probe.
Since virus surfaces have similar structures, the probe can be modified to detect and inhibit other viruses such as COVID-19.
“The beauty of what I do on the platform that we build is that it can be translated to other viruses,” Tawiah said. “So, with the platform for detection, you can essentially do the same thing for COVID, but you have to have the surrogate COVID virus particles…”
Currently, researchers in the lab are waiting for the particles and know the probe can bind to the virus, but they don’t know where exactly it can bind to.
“The lab is interested in using other techniques to find out where exactly the probe binds to on the surface of the virus,” Tawiah said.
While Tawiah is leaving to start his post doctorate in July to further develop low cost diagnostic methods, the Burke lab is continuing to probe for more answers.
Olga Baker, professor of Otolaryngology, will join Bond LSC June 1, 2020, as our newest principal investigator with a focus on inflammation. | photo by Roger Meissen, Bond LSC
By Lauren Hines | Bond LSC
Olga Baker is the type of person who acts when she sees a problem.
In her home country of Venezuela, Baker worked as a dentist who was part of a team that treated head and neck cancer patients.
“They told me how much they suffered as I used to do their cavities and fix their teeth,” Baker said. “That’s how I became so motivated, because I saw their suffering myself.”
These patients stopped producing saliva due to radiation from their head and neck cancer treatments that destroyed their salivary glands.
“Because they look okay everybody thinks they’re normal and they’re healthy,” Baker said. “Nobody knows the suffering that is ongoing inside them, so this brings a lot of psychological burden for these patients.
That motivated Baker to enroll in a biochemistry Ph.D. program at the Central University of Venezuela which she completed in 2003.
Ever since, Baker has been studying salivary glands, tissue regeneration and Sjögren’s syndrome at multiple universities
That passion led Baker to Mizzou initially as a post-doctoral fellow in 2003.
Baker moved from her post-doctoral fellowship to become a senior researcher at Mizzou but left in 2009 for the State University of New York Buffalo to accept an assistant professor position as an independent investigator to gain more experience. In 2014, she then moved to the University of Utah School of Dentistry as a tenured associate professor.
Baker officially returns to Mizzou on June 1 as a full professor in the departments of otolaryngology-head and neck surgery and biochemistry to collaborate with former colleagues as LSC’s newest principal investigator
“I later on decided that it would be nice to be close to home because my husband is from Missouri,” Baker said. “So, working with many people who helped me to be here, I applied to MU and made my decision to come back after seeing all the possible scientific collaboration with great colleagues.”
This time around, Baker will have her own lab to find ways to treat salivary gland hypofunction and to develop the products that sprung from prior work at the University of Utah where Baker created her own business
She aims to further create and distribute saliva substitutes in her business venture using proteins in saliva called mucins. Baker isolates mucins from plants and animals to be used as a mouth spray to moisturize people’s oral cavity who otherwise can’t produce saliva.
“So then with that they can eat better, they can talk better, and that lasts long in their mouth,” Baker said.
Baker plans to bring it to market while working at Mizzou.
Due to having so much expertise in the salivary field, she’s also studying how to prevent COVID-19 from infecting patients through saliva
“COVID-19 is found in saliva, and that’s very important because we could find ways to prevent transmission if you block the entry into saliva. So that’s a new area of interest for my lab.
Baker will be opening her lab on the fifth floor working on inflammation. She plans on being part of the inflammation group at the LSC with Michael Petris and her former colleague Gary Weisman
“I think it will be very rewarding for us at Bond LSC if she locates a lab there because there are people ready to work in her area of research with her,” said Weisman, Curator’s Distinguished Professor of biochemistry.
Baker and Weisman plan on further studying Sjögren’s syndrome, an autoimmune disease that also causes dry mouth, dry eyes and a number of other systemic symptoms.
When Baker isn’t fighting for a cure, she enjoys her other passion — singing and dancing.
She was a lead singer of a band called, Peña Flamenca, who used to play in the Music Café (now known as Café Berlin) and also appeared on a TV show, Pepper and Friends, as part of Hispanic Heritage Month.
Even though she isn’t part of a band anymore, she still dances.
“I really enjoy that part of my life, being a singer and dancing and bringing joy to people,” Baker said.
Baker’s mission is to solve the oral health problems she encountered, and her journey isn’t over yet.
Marc Johnson’s research focus changed suddenly one day this February when he received a shipment. That package of synthesized SARS-COV2 spike genes — the virus that causes COVID-19 — has now taken him down a new path.
“It was unusual, nothing like this has ever happened to me before,” Johnson said, an MU professor of molecular microbiology and immunology and Bond LSC investigator. “I’ve never had to switch directions so abruptly before but, you know, we’re always taking on new projects and shifting, it just usually doesn’t happen as fast.”
Typically, Johnson can be found in his lab studying viral glycoproteins, proteins with sugar attached to them involved in structural functions of the cell wall, and spikes, the knobby proteins on the surface of a cell. His main focus is studying HIV and its interaction with its host. However, his lab got to work right away to apply what they know to find a way to block SARS-COV2, and ultimately, COVID-19.
To do this, they focused on what they know best: glycoproteins and spike.
SARS-COV2 shares both of these features, and, in fact, Johnson has done previous research on other coronaviruses. Glycoproteins and spike allow the virus to attach to other cells. He infects cells with a safe, stripped virus containing the SARS-COV2 Spike and uses trial and error to see what works and what does not.
Early on making the glycoprotein functional was a challenge. Sometimes, when a protein of one virus is taken and stuck on another virus, it does not work. That was the case with SARS-COV2. He decided to cut of the tail of spike to see what happens.
“Most of its [spike] on the outside of the virus. There’s still a little piece on the inside, and if you make the virus smaller they don’t have that inside piece and often work better,” Johnson said, “I couldn’t get anything to work until I made that truncation.”
Without much of the tail, Johnson started looking for ways to block the virus. He has used many methods to find an effective blocking technique.
“We’ve thrown various peptides on and we’ve tested various small molecules,” Johnson said. “We’ve also tried plasma from patients who have recovered to see if they’re producing neutralizing antibodies and, no surprise, they are.”
Antibodies are crucial because they are a sign that someone has an effective defense against the virus. At the very least, antibodies allow the body to keep future infections in check. Taking antibodies from one patient and placing them in another patient passively transfers resistance to a virus and, often, immunity. Researchers are conducting studies to see if this is an effective way of blocking COVID-19.
Having only worked on COVID-19 for three months, there is still a lot Johnson—and the world—does not know.
“80% of people are just like, ‘Yeah, whatever, I’m fine,’ and then others just fall off the deep end. But, we don’t know what’s different. We don’t know why some patients do so poorly and others just shake it off,” he said. “It’s different than anything I’ve ever worked with before. I wake up every morning and it seems like there’s a new discovery every day.”
Working on COVID-19 is much different than working on other viruses, such as HIV. Many scientists are now putting manuscripts of their research online before they are published in hopes of aiding others.
While Johnson is aware that the sooner a vaccine is developed, the better, he knows not to rush things.
“It’s not about having a vaccine, it is about making sure that it’s safe and effective,” Johnson said. “We’re acutely aware that there’s this backlash against vaccines even when they are safe. If you put out one vaccine that wasn’t safe, you would ruin it for all vaccines for generations.”
For now, the search to stop COVID-19 continues and Johnson hopes his work helps come up with a treatment soon.
“We haven’t found a magic bullet yet, but we’ve seen some inhibition with various compounds,” Johnson said, “So it’s a starting point.”
Growing up more than 9,000 miles away in Melbourne, Australia, Michael Petris never thought he would work at MU, especially since he could not even locate the state of Missouri on a map.
Now a professor of biochemistry, Petris was introduced to science early on in his life by his mother, who was a microbiologist and a high school science teacher, who made sure to immerse her children in the science field. He remembers growing up watching Australian wildlife documentaries and being interested in his science classes at school.
After completing secondary school (the Australian equivalent of high school), Petris obtained his bachelor of science degree in biochemistry and genetics as well as a Ph.D. in genetics from the University of Melbourne.
“I was studying the molecular biology of metal nutrition, which is the study of genes and biochemical processes that regulate metal nutrients in the body and how they’re important in disease processes,” Petris said.
A fax led Petris to Mizzou. While working on research as a post-doctoral student, a fax about a job opening at MU arrived in the lab. Petris decided to apply.
“I thought that I’ve got nothing to lose. It’s a tremendous experience to work in another country and to start a lab, and if I’m successful, terrific. If not, I can always go back to Australia and get a job,” Petris said, “This to me represented a once in a lifetime opportunity.”
It is safe to say it was good he took that chance back in 1999.
After his interview, Petris went back to Australia where he later found out he got the position, and he has been at MU ever since.
Adjusting to the American lifestyle was both difficult and easy. There were a lot of things we take for granted that took some getting used to, such as driving on the right side of the road, different types of food, the reverse of seasons, and even being able to understand one another.
“I used to get a lot of people in the community having trouble understanding my accent, which was much stronger back then,” Petris said, despite English being the first language in both the United States and Australia.
Luckily for him, adjusting to the United States workwise was pretty seamless.
“The science side of it is universal. So that was easy,” he said.
Once Petris got his lab set up and running, he began focusing on the biology of the micronutrient copper and how it relates to cancer and infectious diseases. Currently, his lab is interested in developing a drug that can block the transport and delivery of copper to cancer tumors, thus reducing cancer growth.
Petris’ lab looks specifically at the function of copper in a family of enzymes called lysyl oxidases, which have well-documented roles in cancer. These enzymes make the tissue surrounding tumors denser, which encourages the growth and the spread of tumor cells. In diseases such as breast cancer, mammograms are used to detect this increased density in the tissue.
“The drug we’re developing blocks the movement of the copper into that class of enzymes so that we can block the potential for breast cancer and other types of cancer,” Petris said.
While a certain amount of copper is needed in order to stay healthy, Petris explained that by limiting the amount in cancer patients, “Their chances of relapse and the cancer returning are diminished.”
By focusing on regulating copper as a way to prevent cancer long term, Petris’ lab has developed a novel compound that blocks the transporter that takes the copper into the body.
“We’re hopeful that we can develop this small molecule into a drug that could be used therapeutically first in cancer, and, ultimately, for other types of diseases,” Petris said.
In fact, Petris and his Bond LSC collaborators, Dr. Kamal Singh and Dr. Vinit Shanbhag, have submitted a patent application for this compound so that it could be developed for clinical use.
Expanding his research even further, he recently began focusing on ophthalmology and the role copper has on eye diseases as well.
After living in the United States for over 20 years, Petris’ Australian accent is a little less obvious and he does not have to think twice about what is the correct side of the road to drive on. He is happy where he is at.
“Now my research is becoming more applied and translational, I’m becoming even more gratified with the science that I’m doing.”
