The work was tiring. The hours were long. However, Ph.D. candidate Li Su wasn’t affected by any of it. She was in her element
During her undergraduate degree in China, Su studied turfgrass science.
“There was a chance for undergraduates to do some research project, so I tried it and, although it was exhausting, I stayed in the lab and time just passed,” Su said. “I felt quiet and at peace. I kind of enjoyed it.”
As part of the Dong Xu lab at Bond Life Sciences Center, Su works on statistics and data analysis for many research studies throughout Bond LSC.
Originally from China, Su moved to Springfield, Missouri in 2016 to earn her master’s in plant science at Missouri State University. Once she graduated in 2018, she moved to Houston, Texas to work at a biomedical research institution. After a while, she applied for graduate school but wanted to go in a new direction.
“While I was in Houston, at that job, I was confused,” Su said. “I was just thinking about my skills, what I liked to do in the lab and what will make me survive … I realized even a lot of postdocs or senior graduate students were kind of limited in the statistics and data analysis, so I tried to figure out how to do those things.”
Su switched her focus, was accepted by Mizzou in 2020 and soon found her place in the Dong Xu lab.
“As we are trying to handle this big data, the main weapon for us is coding,” said Juexin Wang, Dong Xu’s lab manager. “So, when we are trying to deal with that big amount of data, we have to highly rely on the coding skills and [Su] does that very, very well. She is learning fast and uses all her resources to learn that.”
Su joined the lab while it was strictly Zoom lab meetings and everything was remote. Despite the digital barriers, Su stood out to Wang.
He had found a paper where he believed the lab could replace its methodology with theirs and make the study stronger. Wang mentioned this to Su over Zoom, not thinking much of it.
“Probably weeks later, she came to me and she tells me many things about the other methodology,” Wang said. “So, I was really impressed.”
Su understands what it means to do good science in the lab and what that could mean for others.
“I think a lot of people I work with tell me to be honest with yourself about your science, about your work,” Su said. “I want some work to be like this, so you have a novel idea, you scientifically prove it and make the conclusion helpful to a group of people. I feel like if I have such work, I can be part of the [scientific] community.”
Even though Su isn’t working on any of her own projects right now, her main goal is to publish new and better papers during her Ph.D.
“Smarts, diligence, persistence — I think those are very, very key characteristics,” Wang said. “[Su] is making her weapons much more powerful and much sharper. I think she will get some very good achievements.”
Megan Sheridan, a postdoctoral fellow working with the R. Michael Roberts lab, removes the base solution from a demonstrated sample of stem cells that will be grown into placental cells for study of their interaction with the Zika virus. | photo by Phillip Sitter, Bond LSC
By Lauren Hines | Bond LSC
At 24 weeks pregnant, a baby can hear the mother’s lullabies. At 30 weeks, her belly is a little over a foot large. At 40, the hospital bag is already packed and ready to go.
But imagine delivering only two weeks after the bump starts showing.
Preeclampsia makes induced birth necessary as life-threatening symptoms start 20 weeks into pregnancy, and delivery is the only cure. There is a lack of ways to detect it, and it’s difficult to ethically study the early stages of human reproduction. But what if it was possible to rewind the process to see when the source of the disorder took hold?
Different cellular models of the placenta might be that time machine researchers need to study early pregnancy disorders.
The Michael Roberts lab at Bond Life Sciences Center combines the knowledge and practices of three cellular models to learn more about early pregnancy and diseases.
“We can use these different models to study placental infection with viruses like Zika virus and, of course, COVID because there’s still a controversy as to whether COVID is a hazard in early pregnancy,” principal investigator Michael Roberts said. “And my suspicion is it probably is.”
The placenta is the brand-new organ generated by the embryo — the baby — before any of its other organs develop to give the baby nutrients and support as the embryo grows.
Megan Sheridan, postdoctoral fellow working with the Roberts lab, works on a project to combine 2D and 3D models to see how Zika and Dengue virus interact with the placenta and affect early pregnancy.
“[Complications] occur but you don’t necessarily know that until the end of pregnancy when the baby is delivered,” Sheridan said. “We really want to kind of go back in time and try to determine what’s going wrong in early pregnancy.”
Modeling early placental development is vital to see the beginning of disease complications, but the challenge is to get an accurate glimpse while not putting a healthy pregnancy at risk.
“It’s hard to get a good model to do research on that,” said Jie Zhou, postdoctoral fellow in the Roberts lab. “So that’s why we are working on different stem cells and trying to build up the best model to work on.”
So, the Roberts lab uses the BAP model. By working with a hospital, the lab first takes fibroblast cells from discarded umbilical cords after the baby is born. These fibroblast cells can be collected from mothers experiencing a normal pregnancy or pregnancies associated with complications, like preeclampsia. Then, as Sheridan puts it, they add a “cocktail of genes” to turn the cells into induced pluripotent stem cells. From there, the lab adds BAP — a mixture of growth factors and inhibitors that turn the stem cells into trophoblast cells.
Now the lab is back at the beginning of pregnancy except in a Petri dish of cells. In pregnancy, these trophoblast cells line the outside of the embryo.
“It’s trying to mimic pregnancy in a dish, essentially by using cells that will develop into placental-type cells,” Roberts said.
However, a flat Petri dish is nothing like a real placenta.
“It’s two-dimensional, and we can only culture the cells up to eight days after treatment so if we want to do long-term experiments, we can’t use this model,” Zhou said.
This last model inches even closer to an early placenta. These 3D organoids float around inside a jello-like substance called Matrigel where they self-organize into a placental-like structure.
Together the two models give them a full picture. The 3D model gives a clue into how multiple cell types interact with each other while the 2D model allows researchers to see how a single cell type responds.
Since no model is perfect, the Roberts lab is combining their BAP model with protocols and growth conditions from the other two models to create a foundation for their experiments. Now researchers can start asking deeper questions.
While nothing is quite like a real womb, the Roberts lab will continue working backward.
“All of these models, put together, are really useful because we can kind of use them to their fullest potential and systematically assess which one might represent a certain disease or best answer a certain research question,” Sheridan said.
The best piece of advice Ph.D. candidate Billy Schulze ever received was from his father before a baseball game in high school. In past games, Schulze kept striking out. He wasn’t getting any runs. Things seemed bleak.
Schulze’s father pulled him aside and said with a smile, “Don’t suck.”
“That just kind of made me giggle,” Schulze said. “I think the real message behind that story is don’t think about it too hard. Relax. Have some fun…You can’t take things too seriously, having a sense of humor is so important. Working hard and pushing through problems is vital, especially in science where failure is so common.”
Schulze has brought that mentality to his research in the Margaret Lange lab at Bond Life Sciences Center since he joined in 2019. Whether he’s working on innate immunity or becoming one of the first biomedical engineer graduates at Mizzou, Schulze understands balance is vital in and out of research.
Taking after his father, Schulze wanted to become an engineer. However, it didn’t quite tick all his boxes.
“I have always been fascinated with biology,” Schulze said. “I just distinctly remember being in eighth grade when we went out to the pond water behind my middle school and looked at the pond water with a microscope. Seeing all of the protozoa and stuff that are in the pond water was really cool to me, and that just kind of stuck with me.”
Schulze merged engineering and biology when he became one of the first four students to graduate from biomedical engineering in 2018.
Soon after going back for his Ph.D., Schulze founded the Molecular Pathogenesis and Therapeutics Graduate Student Organization (MPTGSO). It’s aimed at improving the MPT degree by facilitating student feedback to faculty.
“I think that’s the thing I’m most proud of that I’ve done here, just being president of [MPTGSO], founding that and really just trying to be a voice for the entire student body of the program to the faculty in an attempt to just make everybody’s lives better within the program,” Schulze said.
When not helping graduate students, Schulze is in the Lange lab studying viruses, the innate immune systems and what causes Toll-like receptors (TLRs) to activate. TLRs are a class of receptors that can recognize various structures and molecules to trigger an immune system response. The Lange lab focuses on nucleic acid detecting TLRs.
Schulze is using a piece of the poliovirus genome (PV-5) known to bind to these specific receptors to create an immune response to the virus. This allows him to see which receptors activate and why.
“We’re asking what specifically is in PV-5 that is activating the receptor,” Schulze said. “So as opposed to looking at the receptor from the amino acids and what amino acids are required for binding, we’re looking at the RNA, and what RNA structures and motifs are required for binding to TLR.”
The Lange lab is creating a library of RNA sequences based on the genetic information of PV-5 to find which receptors activate.
“In this pandemic-affected world, viruses are at the forefront of health right now, and it’s something that everybody’s thinking about, and we’re specifically looking at the host-virus interface, something that is not necessarily the best understood,” Schulze said. “But at the same time, if we can help to modulate the immune response to viruses, we can potentially have better…potential antiviral therapeutics.”
When Schulze joined Bond LSC in 2016 as part of the Marc Johnson lab, he still had to learn all basic bench skills. Johnson lab supervisor Terri Lyddon was the one who showed him the ropes.
“He was definitely a worthwhile undergraduate student to have in the lab,” Lyddon said. “He was dependable, and he liked the work and came in with a positive attitude every day.”
Lyddon remembers how Schulze was always the one to speak up in lab meetings and ask questions about anything from the lab equipment to why they used particular procedures.
“There are certain levels of enthusiasm and inquisitiveness that come with almost anybody that comes to the lab because you have to want to do this kind of work in the first place…but he brought it to the lab in a unique way,” Lyddon said. “He was curious, and while some others may be curious, they don’t go on to find out the answers to those questions.”
When Schulze’s time in the lab eventually ends, he hopes to move on to a biotechnology company he truly believes in. For now, he’ll be in the lab keeping his dad’s advice in the back of his mind.
“Frankly, I think [science] is a frustrating field to work in, but it is also one of the most rewarding fields for that reason because you’ve overcome so much to find what you found, to prove what you’ve proven,” Schulze said. “I think it’s really cool, but it does require a lot of persistence.”
Arabidopsis plants line the shelves of a basement room in Bond LSC. The new biofortification direction the Angelovici lab found in maize seems to also be present in arabidopsis plants. | photo by Phillip Sitter, Bond LSC
By Lauren Hines | Bond LSC
Whether it’s through kernels, cereal or chips, corn pops up everywhere in our diet, providing nutrition to countless people all over the world.
But that nourishment isn’t enough to be satisfied, especially when a staple so widespread still lacks some building blocks key to balanced nutrition.
Researchers have tried different reverse genetics approaches to making crops like corn, soybeans and rice higher in essential amino acids — building blocks for proteins something the human body can’t produce on its own.
Many approaches have yielded limited success, so the Angelovici lab at Bond LSC took a step back to examine the seed’s nutrition from a broader perspective.
“This is where…we are slightly different than other studies,” principal investigator Ruthie Angelovici said. “We are not focusing just on lysine or just on tryptophane. We’re trying to look at it as a whole to understand the mechanism of all the amino acids composition.”
Finding the mechanism that builds certain proteins means potentially improving the seed’s nutrition. Instead of focusing on specific amino acids, Angelovici’s lab looked toward manipulating a specific process at the heart of amino acid regulation. It found that the process of protein synthesis is strongly associated with certain levels of key amino acids
“It’s super surprising,” Angelovici said. “It’s like saying the factory is responsible for variation we see in some sort of a product. If that’s the case, we can now go and look at the components in this factory that are spitting out this variation.”
It might seem straightforward to genetically biofortify corn, but adding and removing proteins low or high, respectively, in essential amino acids to corn seeds didn’t work. By the next generation of maize, the plant would reset itself through proteomic rebalancing.
“Even if you completely knock out a large amount of storage protein in the seed, the seed has an intrinsic mechanism that it can reprogram, and, ultimately, it can balance those proteins in the seed, so that was very interesting but equally challenging,” said Vivek Shrestha, first author on this study and now a post-doctorate at The University of Tennessee.
Shrestha and others in the lab decided to find which proteins were responsible for the high and low composition of certain amino acids through two complementary experiments.
The first matched amino acids created in the kernel to genes related to them. When that gave a long list of genes, the second experiment whittled it down by finding associations between amino acid compositions and proteins during seed development.
This final list of genes helped Shrestha, Angelovici and others find their new direction.
“We saw a really big group of translational-related genes that seem to be highly dominant in the last piece of the [narrowing down genes process], which we wanted to distill for further inquiry,” Angelovici said. “So, basically what we’ve seen is that the translational machinery is in the heart of the regulation of the amino acid.”
This translational machinery synthesizes proteins and seems to be associated with amino acid composition variations when it wasn’t expected to. This means that there could be something else going on where researchers could manipulate to create more nutritious corn.
“From our paper, it seems that this translational machinery itself probably also has an input that we did not really put a lot of emphasis on,” Angelovici said.
Angelovici believes that this isn’t a corn-specific finding. They reported seeing it in their model plants, Arabidopsis, as well. Next is to experiment with wild mutants of maize and understand its ribosomal footprint.
“I think we had a challenge…but as we go along, we tried to solve them,” Shrestha said. “That’s what scientists are like. They take small steps, remove the challenge and then move forward.
As president of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS) chapter at MU, graduate student Sara Ricardez Hernandez works to connect minority students to research opportunities. | Photo contributed by @MizzouSACNAS on Twitter, Bond LSC.
By Lauren Hines | Bond LSC
Sara Ricardez Hernandez starts her day in the Chris Lorson lab with a vibrant demeanor while wearing her jet-black lab coat. Within five minutes, the graduate student is already at her microscope.
Ricardez Hernandez’s eagerness has only enhanced since she and principal investigator Chris Lorson won the Howard Hughes Medical Institute (HHMI) Gilliam Fellowship on July 22. HHMI created the Gilliam Fellowship and its three-year funding to award and advance diverse and inclusive environments in science.
For Ricardez Hernandez, fostering a healthy, diverse lab environment hits home. Being from Mexico and president of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS) chapter at MU, she knows minority students are often left out of the research career conversation and need opportunities to connect to research.
“I went to [University of Missouri-St. Louis], and I was the only Latina in my whole class,” Ricardez Hernandez said. “I also didn’t really have any mentors that looked like me. I was very interested in showing other people from the same background that they can also be scientists.”
Ricardez Hernandez found out about the fellowship in the middle of an online conference.
“I was super excited,” Ricardez Hernandez said. “I was like, ‘Oh my god!’ And then I went home, and I celebrated it with my fiancé.”
The $50,000 per year will be used to better understand disease and therapeutic developments for the infantile disease spinal muscular atrophy with respiratory distress type 1 (SMARD1). The genetic disorder occurs in children with mutations in the Immunoglobulin-μ-DNA Binding Protein 2 (Ighmbp2) gene.
The Lorson lab looks at SMARD1 in mice to better understand the disease and do preclinical testing of treatments, which fills much of Ricardez Hernandez’s day in the lab.
This involves doing anything from perfusing and dissecting mice tissue to staining mice diaphragms to see if there’s a disruption between the muscle and the muscle nerve cells. Often, Ricardez Hernandez visits the mouse room.
“That’s my favorite part of the day because I love mice,” Ricardez Hernandez said. “They’re so cute. We study an infantile disease, so we mostly use baby mice. These mice can die very prematurely, so if we treat them, they can be rescued.”
Lorson is frequently in and out of the lab helping lab members with their experiments. Lorson has been an important mentor and support system for Ricardez Hernandez even before she joined the lab in 2020.
“It was my first semester of my Ph.D., and I really wanted to go to the [SACNAS] national conference,” Ricardez Hernandez said. “We needed some funding, and [Lorson] being in the veterinary school was like, ‘Oh, I heard that you’re looking for funding. I know someone who can help you with that,’ and it was himself.”
Lorson’s mentorship may have rubbed off on Ricardez Hernandez a little since it’s now a passion in her daily life. Usually, she’ll work with undergraduates in the lab and meet with her mentees from the Maximizing Access to Research Careers/Initiative for Maximizing Student Diversity (MARC/IMSD) program after work. Then, she’ll help students as a teacher’s assistant for a microbiology class.
“She’s honestly an inspiration for any minorities seeking medicine, research, or higher education,” said Zayd Al Rawi, an undergraduate in the Lorson lab. “Although I come from a different background, being Middle Eastern, we share the commonality of being minorities in America, so I see her as a role model. She’s a true inspiration to minorities seeking their goals.”
The Gilliam Fellowship will help Ricardez Hernandez advance her research and gain her Ph.D. in molecular pathogenesis and therapeutics. Until then, Ricardez Hernandez will spend her afternoons helping students and quantifying data with her favorite show on in the background.
“Overall, [she’s] one of the best people, best researchers, and one of the best supportive mentors that I’ve met,” Al Rawi said. “I’m really glad that I’m in this lab and I’ve crossed paths with her. I know she’s going to continue doing great things in the future.”
More information on the HHMI Gilliam Fellowship can be found here, and information on the Mizzou SACNAS chapter can be found on their website.
Increasing detection of reinfections and rediscovering brand new infections within days raises concerns for herd immunity and the durability of vaccine efficacy.
Cynthia Tang working to figure out how COVID-19 reinfections can bring us answers on how the virus is developing at Bond LSC. | photo by Davis Suppes, Bond LSC
By Davis Suppes | Bond LSC
Like many viruses, SARS-CoV-2 continues to develop and evolve with time. As the virus evolves it becomes more infectious and can produce worse symptoms and a higher fatality rate. While more people have been infected, we also learn more about it, including how different variants of the same virus can reinfect someone who already had SARS-CoV-2.
In a recent study led by Cynthia Tang, an MD-PhD student at the University of Missouri (MU) School of Medicine and Institute for Data Science and Informatics, her lab was able to identify a patient who got reinfected with a different strain of SARS-CoV-2 just 19 days after their initial infection. Her Systems Biology Laboratory is headed by Principal Investigator, Dr. Henry Wan, who directs the MU Center for Influenza and Emerging infectious Diseases.
“We found a case of reinfection that occurred during a shorter window of time than what we see in the current US Centers for Disease Control and Prevention (CDC) guidelines,” Tang said, “so we may be missing a subset of those reinfection cases.”
In October 2020, the CDC published investigative criteria for suspected SARS-CoV-2 reinfections. These criteria included: any individuals testing positive over 90 days after their first laboratory-confirmed SARS-CoV-2 infection, or symptomatic individuals testing positive 45–89 days after initial infection with paired respiratory specimens.
For this patient, nineteen days following her initial positive test in March of 2020, she returned for another SARS-CoV-2 test due to return-to-work requirements. Despite her symptoms fading to encompass only productive cough and fatigue she tested positive again. She continued to experience persistent cough, fatigue, and difficulty breathing until 55 days after her initial positive test.
Tang showed that the two samples contained two infectious variants of SARS-CoV-2 viruses. No diverse polymorphisms, or a mixture of different viruses, were identified among the sequences of the viruses from each clinical sample, suggesting true reinfection rather than a coinfection. One good news is that this case also suggests that reinfections may not be worse than the prior infection.
The CDC has encouraged symptom-based strategies for ending isolation rather than viral retesting for asymptomatic individuals or for individuals without new symptoms during 90 days after illness onset due to findings that detectable but noninfectious SARS-CoV-2 RNA can persist in respiratory samples. This means that even if you don’t exhibit symptoms there could still be traces of SARS-CoV-2 in your system, and those traces could be from an original infection or a reinfection.
This study suggested that reinfection could pose a challenge to infection control, especially as the Delta variants are surging around and new variants continue to emerge.
“People showing influenza-like illnesses are recommended to isolate themselves for ten days or wait for their symptoms to go away. We may not be catching cases where individuals contract another COVID-19 infection within a short amount of time,” Tang said.
“The COVID-19 vaccination has been proven to be effective in reducing the chances for people to become infected and reinfected”, Tang added.
Research refines platform to address immune disorders
Dr. Esma Yolcu and Dr. Haval Shirwan, Co-pioneers of ProtEx technology
By Davis Suppes | Bond LSC
The things that protect you can also cause the most harm. That’s especially true when it comes to your immune system, which protects you against infections, but is also responsible for a host of diseases, including autoimmune disorders, such as type 1 diabetes.
More than 1.4 million Americans suffer from the self-harming condition of diabetes without an effective cure, but researchers Haval Shirwan and Esma Yolcu may have the answer.
The pair tackle the problem of diabetes and other autoimmune disorders by targeting the component of the immune system that does harm for modulation. DNA-based gene therapy has traditionally been used as a scheme to modulate the immune system.
“DNA-based gene therapy is a complicated, exhaustive and expensive technology,” said Shirwan, a NextGen Precision Health researcher at the University of Missouri and a professor in the Department of Child Health and Molecular Microbiology and Immunology at the School of Medicine. “We wanted to see if there was a more efficient and practical way to do immunomodulation.”
For conditions like Type 1 diabetes, where the immune system misfires and destroy beta cells producing insulin, they target to replace defective islets with healthy ones from another individual. Insulin is an important hormone that plays a role in regulating your blood sugar level. A major hurdle for islet transplantation is the immune rejection.
Shirwan and Yolcu co-pioneered ProtEx™, a proprietary platform that allows for generation of novel recombinant immune ligands and their positional display as single agents or in combination on biological surfaces, such as islets. This is a practical and safe alternative to gene therapy for localized immunomodulation.
In traditional methods of gene therapy, DNA must first be introduced into the cell, but ProtEx technology bypasses that step. Sticking the protein directly on the cell surface for immunotherapy via a test tube allows for a safer, more effective method than gene therapy. Islets engineered to stick on their surface proteins evade rejection by the immune system.
Shirwan’s translational research program’s goal is to develop safe and practical immunomodulatory approaches with applications to transplantation, autoimmunity, cancer, and infections. On the cancer side, Shirwan and Yolcu team has shown that the immune system of a healthy individual can be trained to surveillance the body for cells that may transform into cancer and eliminate them before cancer takes hold. “This is an exciting finding that has not been reported in the literature and sets the stage for
Shirwan’s focus of learning about the immune system and improving it came to him very early when he was a virologist for University of California, Santa Barbara. He developed an interest in immunology and wanted to learn more about immune defense mechanisms. Before bringing his talents to Mizzou he also spent time working at the California Institute of Technology, Allegheny University of the Health Sciences, University of Louisville, and Cedars-Sinai Medical Center.
He believes preventing these cancers and infections is the route we should be aiming toward, rather than trying to find new ways to treat them after they have already damaged the body to an extent.
“Things like cancer are so effective and harmful because they use the same mechanism as the immune system to evade it,” Dr. Shirwan said, “Just like how a runner can build muscle memory for running, our immune system can learn and build up a memory of these pathogens and infections to create a more effective response.”
“This is just the tip of the iceberg,” Dr. Shirwan said, “I am very excited to continue expanding on what our immune system is capable of.”
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.
Dr. Shirwan and his team are moving to the new NextGen building on Mizzou’s campus in mid-September. He is very thankful for getting the opportunity to work in these facilities with these people, and he is excited for the next step of their research.
Shirwan believes we have only scratched the surface of what our immune system is capable of. Our immune system may not always know what is good and bad for itself but one thing is for sure, Dr. Haval Shirwan is good for it.
Saathvik Kannan, Kamal Singh, and Austin Spratt, worked together at Bond LSC to identify new SARS-CoV-2 variants. | photo by Davis Suppes, Bond LSC
By Davis Suppes | Bond LSC
Variants of the virus that causes COVID-19 continue to plague the world with spikes in infection, keeping the current pandemic from being fully controlled as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections remain unmanageable in some parts of the world.
Researchers at Bond Life Sciences Center and the University of Nebraska Medical Center (UNMC) have been conducting research on mutations in four new variants, B.1.1.7, B.1.351, P.1 and CAL.20C. These evolving variants appear to be more infectious and transmissible than the original Wuhan-Hu-1 virus.
It all started with a new spike in infections of a variant of SARS-CoV-2 in the UK. Despite a slowdown in infections due to precautions of masks and lockdowns, the new spike meant something about the virus had changed.
“Our goal was to find out where these variants are distributed, and how they are migrating,” said Kamal Singh, Assistant Director Molecular Interactions Core, and scientist at Bond LSC. Singh was a corresponding author on the paper and has been at Bond LSC for 12 years.
Their work showed completely different mutations in these variants based on regions, but also where variants have common lineage. That commonality can be seen between the CAL.20C and B.1.351 variants.
While related to each other, they also developed different mutations.
“B.1.1.7 was more infectious and was able to spread to more people. It slowly dominated and that’s what happened in the United States as B.1.1.7 is now the dominant variant of SARS-CoV-2 in the US,” said Saathvik Kannan, a co-author. Kannan is going to be a 10th grader at Columbia’s Hickman High School this fall but works under Singh at Bond LSC as a computer programmer and researcher.
Once they identified the related COVID-19 variants, they wanted to trace their migration. This allows them to see where the mutations are being carried and which regions have a more dense number of infections. The prevalence of variants was key in identifying where they were moving.
Their analysis looked at certain mutations in each variant to see how they were related, why some sequences have mutations that others don’t and tried to determine how they evolved from their original sequence.
By comparing the structure of each virus, they were able to illustrate how the related mutations moved state by state across the country.
This Sankey diagram for variant CAL.20C in the United States.They aligned the first-known CAL.20C sequences from each state then grouped the sequences based upon the date collected and closely their structures matched, with cut-offs of 96, 94, 93, 92, 91 and 90 percent compared with the previous group.
“It is pretty clear that some states have a higher homology match, which helps us see a pretty linear trend of migration from the Western states to the East in the United States,” said Austin Spratt, a computer science senior and lead author on the paper. Spratt has worked under Singh at Bond LSC for two years.
The study cautions that the sequences of viruses are being deposited at an unprecedented rate, so it is possible that some conclusions may change as more sequences of variants become available.
“These variants are continuously evolving and complex in nature, but a proper understanding of what makes each variant unique, its genetic makeup and its interaction with host proteins is critical to developing the most effective vaccine,” said co-corresponding author Siddappa Byrareddy, Professor & Vice-Chair of Research, in the Department of Pharmacology & Experimental Neuroscience, at the University of Nebraska Medical Center. “Not only will this help us to design better vaccines now, but greatly help us to be prepared to deal with more mutant variants in the future.”
Although analysis indicates that mutations only in one variant do not reflect evolution of it, these genetic mistakes may increase infectiousness of a particular variant
The short period of time, volume of variants and limited travel around the world all point to a greater infectivity than the original (Wuhan-Hu-1) virus. Recent deadly surges in India caused by variant B.1.617.2 or the Delta variant will soon be added to their analysis to further understand the COVID-19 pandemic.
Their research was published in the paper ‘Evolution, Correlation, Structural Impact and Dynamics of Emerging SARS-CoV-2 Variants’ in the “Computational and Structural Biotechnology Journal” on June 19, 2021.
Funding provided by: Bond LSC, Swedish research Council, American Lung Association, National Institute of Dental and Craniofacial Research in collaboration with Prof. Gary Weisman of the Bond Life Sciences center.
After 40 years of hard work, it is finally time for David Pintel to pass the torch.
Dr. David Pintel, retiring after 40 years at Bond LSC, takes in his office during his last week at Bond LSC. | photo by Davis Suppes, Bond LSC
By Davis Suppes| Bond LSC
David Pintel is hanging up his lab coat after 40 years.
“It’s been an honor to be able to do my work at the University of Missouri. I’ve had a great group of colleagues both here and at the medical school,” Pintel said.
The Bond LSC virologist retired July 1 after a storied career. He spent 20 years at the School of Medicine before joining Bond LSC upon its completion more than 15 years ago.
Since then he has aimed to better understand the interaction between viruses and host cells. Pintel specialized in the study of parvoviruses, the smallest of all DNA viruses that infect vertebrates. In addition, the parvovirus adeno-associated virus (AAV) has been developed as a promising gene therapy vehicle.
On his last official day in his office Pintel was busy still packing up old memories while taking everything in.
“I’ve had tremendous students and tremendous colleagues, you know they were the important parts of my career,” Pintel said, “Going through all the old memories, you know, it’s gonna take a little while”
Pintel is a Curators’ Distinguished Professor as well as a Dr. R. Phillip and Diane Acuff Endowed Professor in Medical Research Molecular Microbiology and Immunology. He reflected on fond memories of his work here, but when asked what his favorite memory was his answer was the same, working with all of these people.
“It’s an emotional end, when you do something every day of your life for 40 years,” Pintel said. “I’m so thankful and grateful for the people that have worked with me, people that have been my friends here and allowed me to have a successful career.”
The future for Pintel will come in due time, but for now he is in no hurry and plans to enjoy some time off.
“To be determined,” Pintel said, “I think I will decompress for a while before I make any decisions on the next step.”
Lyndon Coghill is the new Director of the Bioinformatics and Analytics Core, and he is already making big moves at Mizzou.
Lyndon Coghill, Director of Bioinformatics and Analytics, stands near his office on June 22 at Bond LSC. | photo by Davis Suppes, Bond LSC
By Davis Suppes | Bond LSC
Lyndon Coghill’s official title may be Director of Informatics for the Bioinformatics and Analytics Core, but his job branches out much wider than just a single label. Even as an undergrad, Coghill wore many different hats.
“I was incredibly excited about the way that the MU Office of Research and Economic Development recruited me,” Coghill said, “With these types of processes you can get an idea as to whether or not an institution is actually committed and excited about building something out.”
With his experience and range of expertise, Coghill was an easy choice for Mizzou to fill the role of Director of the Bioinformatics and Analytics Core located at Bond Life Sciences Center.
Before he achieved his doctorate in biology, he completed his undergraduate degree in zoology with minors in microbiology and geology at Western Illinois University. For his dissertation, the research he conducted was focused heavily on evolutionary genomics. Simply put, he wanted to know how changes in the genome lead to changes in a physical organism that allow them to adapt better to different environments and conditions.
With his doctorate in biology, he would go on to his first postdoc at The Field Museum of Natural History in Chicago in 2013, and then on to Louisiana State University where he began his role as a senior post doctorate in 2015. He continued to diversify his portfolio there working with the department of biology, focusing on computational biology. He was then promoted to research data scientist which had him take on an even more computationally heavy role. With this, he was able to help biologists learn how to talk to computer scientists, and assist them with building collaborative programs together..
As director, Coghill’s mission is to provide bioinformatics and data science support to all researchers across the UM system. He is creating a central hub where faculty whowant toconduct domain- specific biological or life sciences-related research that is computationally heavy can get the help they need to come up with solutions. He does this by helping researchers wrangle incredibly large datasets and by helping them understand what that data is telling them from an information perspective in a meaningful way.
Coghill mentioned how interim Vice Chancellor of Research and Economic Development Thomas Spencer also made a personal effort to make sure Coghill understood his vision going forward on campus “and for me that was enough of a selling point that I wanted to be a part of that,” Coghill said.
In addition to the thorough recruitment process, Mizzou’s facilities and access were other huge factors that Coghill was looking forward to once he got here. With a hospital, vet school and productive biology program all on the same campus instead of in different cities, Mizzou offers a unique opportunity to build the integrated program all in one place.
“We’re trying to reach out to every department on campus to build these relationships because you can’t have true integration of ideas and solutions if you don’t talk to everyone who might be a benefactor or have knowledge about that,” Coghill said.
Coghill believes that to create a phenomenal translational research program, this core must interact with all these programs so that experts of different fields can come together to collaborate.
“Informatics research, especially bioinformatics is a program that really forces you to keep one foot in both worlds of computer science and biology, and there’s a limited number of peoplewho do that kind of work,” Coghill said, “I think that was one of the big pushes for getting my experience here for this position, to bring in somebody who could bring these programs together and integrate across all these different fields.”
Coghill is excited to be working with the variety of researchers and programs across the MU campus and UM System, and learning from them at the same time.
“We may not know their biological system as well as they do and we may not know the high performance computing system as well as a full-time systems administrator, but we know enough of both that we can communicate with both teams and make sure that we can help get the researchers from the starting point to a meaningful result,” Coghill said.
Their goal is to provide Mizzou and sister campuses with research support allowing faculty to build translational research programs using computing power and informatics. This core brings new opportunities for Mizzou students as well.
“We’re going to have programs for students that can rotate through as part of the Informatics and Data Science Institute,” Coghill said.
This means that students who are interested in research fields can get direct experience related to career possibilities outside of Mizzou and academics by working in this program.
“Students can come to us and learn basic coding skills, learn informatics and bioinformatics, and that will help them build a skillset that will make them quite employable,” Coghill said.
Between helping researchers in their labs and analyzing quantities of data they are gathering for the first time, Coghill has a variety of jobs he has to understand and execute.
“So, I am the guy who wears a lot of different hats and allows these researchers from different domains to talk to each other,” Coghill said. “We’re trying to help them get to the point where their work could be as big as they want.”
Mizzou and Coghill know that there is no way to push modern research without computing, especially at the scale research is done today.
It would be extremely rare for someone who has a doctorate and spent their life trying to understand how one particular part of a biological process works to also have a doctorate in computer science, “That’s where we help… we’re providing researchers with the tools to do research at a scale using computing power, and asking questions that for many, might have only been dreamed about at other times in their careers,” Coghill said.
