Kiefer, Sarah (MU-Student)

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MU researchers see future where gut microbiome could help detect colon cancer earlier

December 13, 2023 By Kiefer, Sarah (MU-Student) in Faces of Science, Research Tags: colon cancer, James Amos-Landgraf, Lloyd Sumner

James Amos-Landgraf and Lloyd Sumner — Lloyd Sumner (left) and James Amos-Landgraf teamed up to work on colon cancer research shortly after Sumner joined Bond LSC in 2016. | Photo by Sarah Kiefer, Bond LSC

By Sarah Kiefer

Could there be a better way to detect colon cancer than a colonoscopy? A less invasive test might depend on its association with microbes in the gut.

University of Missouri researchers looked at the overall microbiome in a rat model of human colon cancer to discern how differences in the bacteria affect adenomas, benign tumor growth that frequently is precursor to colorectal cancer. Those changes translated into a measurable difference that doctors could one day use to get a jump on this second leading cause of cancer death.

James Amos-Landgraf, an associate professor of veterinary pathobiology, worked with Lloyd W. Sumner, a professor of biochemistry and Bond Life Sciences Center researcher, on a multi-omics approach to analyze the molecules created by cell processes. By measuring large numbers of metabolites — small molecules that act as building blocks or energy sources for an organism — the team found when a unique combination of bacteria and metabolites are present, they correlate with higher susceptibility to colon cancer before any observable symptoms exist.

“In the rat model studies we could classify the severity of the cancer and tumor loads based upon earlier metabolic profiles,” Sumner said. “If you could achieve the same in people, the metabolic profiles could be used as a prognostic tool which would allow better alignment of treatments with the predictive severity. For example, you might want to be more aggressive with treatments in more severe cancer patients.”

Colorectal cancer is the second leading cause of cancer death and, currently, the only way to definitively diagnose it is to get a colonoscopy. If the adenomas are found and dealt with early, the survival rate is high.

This gut microbiome research is one of the projects Amos-Landgraf has been working on for the past 10 years, and the multi-omics approach sets it apart from the microbiome research of peers. Most experiments pick apart one or two bacteria samples and place them into an otherwise germ-free animal to see what happens, but the team wanted to analyze the entire stew of microbes present. Bacterium do not live alone, so what happens when the other bacteria recognize the new guy in the room?

“We know bacteria live in a community just like we do, and not everybody does the same job,” Amos-Landgraf said. “Just like we wouldn’t have the same lifestyle we have without someone providing our electricity, gas, or other utilities, the bacteria have requirements of their own.”

Amos-Landgraf and Sumner looked at this bigger picture, something they first partnered on in 2016. Sumner used his metabolomics expertise to profile and draw conclusions from the rat fecal samples.

“While this paper might not be foundational because other papers have noted several specific metabolites associated with cancers, it is a progressive step in the right direction towards better understanding of the metabolic relationship between the gut microbiome and forms of cancer,” Sumner said.

The analyses helped researchers find similarities and differences in small molecules present in rats with tumors in their colon versus those without.

“I think we have a scientific platform to really study these differences in more detail in a controlled system,” said Amos-Landgraf. “While we can now see a visible difference, this still leaves a lot of challenges to overcome and to answer.”

By looking in tandem at the transcriptome — the full range of messenger RNA that tells cells how to make proteins — they also saw what genes were turned on and off and correlated that with tumor presence. With tumors, they saw increases in biological processes to create bile for fat absorption, fatty acid breakdown and mucin that lubricates the gut. The team found certain species of bacteria in the gut microbiome gave way to specific metabolites and influenced genetic changes that turned off a gene that would normally suppress a tumor.

This sort of analysis is possible because of the advanced tools in MU’s Metabolomics Center.

Previously the way to study gut microbiome within the body was to look at the evidence and build a hypothesis from there in a sequential manner, which takes time and money. Now, the team can perform discovery based metabolic profiling on a larger scale with high resolution instruments that organize and categorize metabolites without having to test and re-test a hypothesis until they find a perfect fit.

“I’m an analytical chemist by training and I like instrumentation, but instruments cost money and they must solve problems,” said Sumner, who is also the director of MU’s Metabolomics Center and professor of agriculture biochemistry at the University of Missouri. “This is a project that utilizes problem solving and new knowledge, making it a measurable outcome. We just need one hundred more like it.”

Metabolic profiling is achieved through a series of a few experiments where the team uses gas and liquid chromatography to separate complex mixtures of metabolites. For example, gas chromatography uses a small, hollow tube coated on the inside that appears to be a piece of fishing wire to the naked eye. Samples are injected into the column and they move through this column to ultimately separate in a series based upon chemical interactions specific to each small molecule.

Metabolites are placed into an ultra-high pressure liquid chromatography machine to achieve the gas phase in each sample. The machine can handle hundreds of metabolites and is an essential step in categorizing the weight and identity of each sample. | Photo by Sarah Kiefer, Bond LSC

The chromatography system is coupled to a mass spectrometer that serves as a detector and weighs the molecules as they elute or are removed by washing with a solvent. The molecular weight helps to identify the metabolites. These methods provide an overview of some 1000 to 1500 metabolites that may change over time.

“A lot of my research is focused on building tools to help with the identification process of these molecules,” Sumner said. “Mass spectrometer will give us an accurate mass and molecular formula, but it doesn’t always tell us how those atoms and molecules are connected together.”

In these situations, they use nuclear magnetic resonance spectroscopy (NMR) which identifies molecules by irradiating and listening to responding radio frequency levels and matching them to a structure.

In 2022, a partnership with Stanford University led to placing a humanized microbiome into a mouse, creating a better model for studying our gut bacteria. Amos-Landgraf wants to do the same thing with their genetically modified animals to see how it affects those susceptible to development of cancer.

The next step for the team is to identify whether this metabolite correlation truly means a direct genetic relationship between these bacterial species, tumors and colon cancer.

The project could lead to more diagnostic tests in order to identify cancers early on in a patient’s history or it could be as simple as prevention through the taking of supplements or probiotics. Getting to the guts of this issue is what the project is all about, so they must take this information and dissect it to draw accurate conclusions.

“Science doesn’t happen in a vacuum and one of the reasons that people stay in science is because they want to solve a piece of the puzzle and step back to study how and why it comes together,” Amos- Landgraf said.

The paper titled, “Integrated multi-omic analyses provide insight into colon adenoma susceptibility modulation by the gut microbiota” by Susheel Bhanu Busi, Zhentian Lei, Lloyd Sumner, and James Amos-Landgraf was first published in the American Society for Microbiology journal mSystems on July 17, 2023.

OPEN leaf system offers affordable, automated option for plant data collection

December 8, 2023 By Kiefer, Sarah (MU-Student) in Research Tags: David Mendoza, Landon Swartz, OPEN leaf system, plant science

Landon Swartz, a graduate research student at the University of Missouri in the David Mendoza-Cózatl  lab at Bond LSC, looks at the camera on the OPEN leaf machine and makes adjustments to the plant the robot is photographing. | Photo by Sarah Kiefer, Bond LSC

By Sarah Kiefer

The LED lights danced as the OPEN leaf system powered up. Quickly, the robot zips down the track to its preplanned destination, hovering above each plant sitting atop a 3D-printed mechanism, then the camera snaps a shot as it conducts this same routine every 30 minutes.

This open source, data driven tool is one way scientists like David Mendoza-Cózatl lab at Bond LSC and work to simplify the tedious data collection required in plant research.

The OPEN leaf system — described in The Plant Journal in September 2023 — uses modern technology to do its job better and gather results faster than other machines of the same kind. But this National Science Foundation funded project is more than just a robot taking a picture of a plant.

The camera for the OPEN leaf system travels across its track, snapping photos of the growing plants along the way. | Photo by Sarah Kiefer, Bond LSC

“Phenotypes are a change in a plant that you can visualize. Our goal is to characterize phenotypes through time,” said Mendoza-Cózatl, a Bond LSC researcher, director of graduate studies and associate professor of Plant Science and Technology at the University of Missouri. “In my mind, time is one of the black boxes that we have not been able to solve because it is variable.”

Color plays a big role in measuring change in a plant. Using color quantization techniques that simplify colors into numbers, researchers can identify four basic colors to analyze. The machine captures RGB (red, green, blue) images using a camera and converts it into a LAB color space to do the heavy lifting. L stands for lightness, whereas A and B represent the green to magenta and blue to yellow color spectrums detected in something like a leaf of the plant.

“Color is a subjective thing to a lot of people and it’s a lot easier to look at a number and say this number is more than this number, but saying this color is more yellow than this one is a harder thing to recognize,” said Landon Swartz, the Mizzou computer science graduate research assistant who engineered the system. “Our process correlates the human perception of color which is actually very different from the way a computer sees color.”

Landon Swartz is a graduate research student at the University of Missouri who engineered and worked on the OPEN leaf system in the David Mendoza-Cózatl  lab. | Photo by Sarah Kiefer, Bond LSC

When the colors are quantified, then the real work begins — plotting the points.

This procedure morphs a primarily visual measurement into a mathematical one. Just like with numerical data, Swartz can take colors and observe how they change over time by using coordinates from his simplified combinations.

“It’s a really dynamic process and something that’s not thought about a lot, but because no one’s ever done it before, it’s very hard to convince people it’s accurate and try to visualize or explain the process to others,” said.

Mendoza-Cózatl  said this way of quantifying and recording takes the system to the next level.

“We thought this idea of describing color through time was solved a long time ago. Turns out, it was not,” Mendoza-Cózatl said. “Extracting the color of a plant has been done, but representing the color to viewers over time is something that has not been done.”

The team differentiated their system from others by considering a hybrid work environment to allow many collaborators through the Slack communication app. The app can be used to chat directly with the robot itself.

“We are trying to advance the field of phenotyping as a group,” Mendoza- Cózatl said. “It’s not just my machine, it can be your machine or anyone’s machine.”

Slack was first suggested by Drew Dahlquist, a former undergraduate in the Mendoza-Cózatl  lab, during the COVID-19 pandemic when research labs needed to cut out the middleman on projects that require collaborators from afar.

“Let’s say I’m sitting in my basement, the experiment is running and I want to know how it’s going. I can message the machine ‘hey, can you send me the last couple of pictures that you took’ and the machine will send them,” Mendoza-Cózatl said. “The element that sets this system apart is you can then share it with colleagues, students, or anyone.”

Swartz and his collaborators worked to incorporate the details of the plant, not just the entire rosette — the circular arrangement of leaves on the plant. Their system recognizes each individual leaf without bias.

But how can observation of a leaf be biased in the first place?

Traditionally, these systems prompt the user to draw a line around each leaf for it to be recognized, which is a subjective observation based on how each person draws their boundaries.

The OPEN leaf system’s computer algorithm automatically recognizes each leaf to be analyzed separately.

The Arabidopsis thaliana, a model organism plant that Swartz works with sits on top of 3D printed plastic floaters that create a hydraulic watering system while the camera continues to take photos when prompted. | Photo by Sarah Kiefer, Bond LSC

“To me it’s really exciting because I was trained as a biochemist then I decided to work with plants. I never thought I would be publishing papers about computer vision and phenotyping,” Mendoza-Cozatl said. “It gives a fantastic example that science is really open. We saw a need, so we tackled the problem and came up with a solution that is very rewarding.”

Their new machine also makes the database more accessible and cheaper than other similar machines. Costing less than $3,000 to build, the blueprints and instructions to build the OPEN leaf system are accessible to anyone who wants to put it together.

“This type of project shows that you can do a lot with a little because you don’t need to pay thousands of dollars to get the same amount of insight into your research,” Swartz said. “This project has become a tool that we are going to use for papers to come, and we are hoping that other people will start to use it for their papers as well.”

The collaboration between engineers and biologists helped them address the evolving nature and nuanced challenges of the project.

“The most interesting part about this project is that there is a novelty to working in an interdisciplinary manner like this,” Swartz said. “Usually, how it works is someone comes to you with a problem and you present a solution. But here we are coming up with solutions to find the problems, which I think is a very fruitful approach.”

Swartz is already working on his next big project — an OPEN root system. This machine will accomplish similar goals but apply to the root system of the plants instead of the leaves.

The paper titled, “OPEN leaf: an open-source cloud-based phenotyping system for tracking dynamic changes at leaf-specific resolution in Arabidopsis” by Landon Swartz, Suxing Liu, Drew Dahlquist, Skyler T. Kramer, Emily S. Walter, Samuel A. McInturf, Alexander Bucksch, and David G. Mendoza-Cózatl was first published in The Plant Journal on September 21, 2023.

Libault returns to Bond LSC as plant scientist with single cell focus

November 13, 2023 By Kiefer, Sarah (MU-Student) in #IAmScience, Faces of Science, Research Tags: CAFNR, Marc Libault, MizzouForward, plant science, single cell biology

A picture of Marc Libault, a new Bond LSC principal investigator and professor of professor of plant science and technology in the College of Agriculture, Food and Natural Resources at the University of Missouri. — Marc Libault, a new Bond LSC principal investigator and professor of professor of plant science and technology in the College of Agriculture, Food and Natural Resources at the University of Missouri. | Photo by Sarah Kiefer, Bond LSC

By Sarah Kiefer | Bond LSC

Marc Libault only ended up one floor up from his old stomping ground in his recent move.

Libault — the most recent MizzouForward hire at Bond Life Sciences Center — returned this fall to bring his expertise in plant single cell biology to MU.

“What is exciting about this research is its innovation to generate a new knowledge in crop science; we’re the first group in the world to develop a very broad application of single cell biology in plants,” said Libault, Bond LSC principal investigator and professor of plant science and technology in the College of Agriculture, Food and Natural Resources. “I was excited to come back here to continue to work on solutions at the single cell level notably by working in collaboration with experts in proteomics, metabolomics, and phenomics at MU.”

Single cell biology is exactly what it sounds like: singling out individual cells in a plant in order to reveal their unique molecular features and mechanisms. This field can help scientists better understand the functions of different genes and proteins.

“If you want to engineer a complex machine such as a car, to enhance its performance you need to first understand the nature and the contribution of each part and how they work together,” Libault said. “In plants, you need to understand how each gene contributes to the biology of the cell and how each cell plays a part in the entire plant before creating meaningful genetic strategies to enhance crop biology. Having this more accurate picture allows us to enhance our current knowledge in plant and cell biology.”

While cutting and chopping are more common descriptors in cooking, researchers in Libault’s lab chop a plant sample in order to isolate the nucleus of the cells to study gene activity. His lab also focuses on spatial transcriptomics, a process that looks at how cells use their genes within the organs they inhabit. If they can understand the contribution of each cell in the plant and how they are interacting with one another, they can grasp how they work together to respond to environmental stressors.

“In society, each individual has unique competences and expertise. They work together to accomplish one goal. That’s similar to cells with unique functions working together in an organs to support its function,” he said.

By pooling this information together, they hope to identify important regulators that control how other genes are expressed then manipulate those molecular chains to see how the plant improves.

Libault is not exactly a newcomer at Mizzou.

Back in 2005, Libault came to MU from Paris, where he grew up. He worked as a postdoc in the Gary Stacey lab until 2011 when he became an assistant professor at the University of Oklahoma. He stayed there until 2017 when he moved into an associate professor position at the University of Nebraska. He got his bachelor’s degree from Denis Diderot University in molecular and cellular plant physiology and his master’s degree from Pierre et Marie Curie University in cellular biology and physiology. He went on to earn his Ph.D. in molecular and cellular plant physiology from Paris-Saclay University.

But, Libault’s last 20 years of research have been focused on understanding the mechanisms controlling gene activity including the role of epigenetics — the study of how environment and behavior change the way your genes work — helping him tackle questions like “how does the expression or repression of genes change from cell to cell?” This gives him a unique perspective as he learns to recognize the systems behind gene activity and apply that to his work on a single cell level.

The interaction between roots and bacteria is one of the areas of exploration of the Libault lab at the single cell level. In legumes like soybeans, bumps called nodules grow on the plant roots to facilitate the relationship between plant and bacteria. This nodulation gives the bacteria a place to live while it converts atmospheric nitrogen into food for itself and the plant.

“The bacteria capture the atmospheric nitrogen and convert it into a source of nitrogen supply for the plant,” Libault said. “In return, the plant will give sugar to the bacteria, which is why the two help each other.”

Outside of the lab, Libault enjoys watching Formula 1 racing or movies from the ‘70s and ‘80s in his free time. He is also interested in keeping up with French and European news. Although his balance between work and home life can become challenging at times, when things get hectic Libault prioritizes family time with his wife and three teenage boys as they continue to settle into Columbia after a few years apart.

Libault has been able to hit the ground running in his lab because much of his team made the trek south with him from Nebraska in September.

Group picture of the Marc Libault lab members at Bond LSC. — The Marc Libault lab at Bond LSC. From top left to bottom right, Sutton Tennant, master’s student; Marc Libault, Bond LSC principal investigator and professor of plant science and technology in the College of Agriculture, Food and Natural Resources; Sahand Amini, postdoctoral fellow; Md Sabbir Hossain, Ph.D. student; Sandra Thibivilliers, research specialist II; Hong Fu, lab technician; and Hengping Xu, postdoctoral fellow. | Photo by Sarah Kiefer, Bond LSC

Libault’s work necessitates collaboration to bring all the pieces together, and that’s what drew him back to MU.

“I know how collaborative the university and the researchers working here are, so that was a strong motivation for me to come back here and continue that kind of collective work,” Libault said. “What we have developed has been highly successful and that’s fun, but what’s next? What more can we learn? This is just the beginning of my next 25 years of research.”

MizzouForward is a transformative, $1.5 billion long-term investment strategy in the continued research excellence of the University of Missouri. Over 10 years, MizzouForward will use existing and new resources to recruit up to 150 new tenure and tenure-track faculty to address some of society’s greatest challenges. Investments also will enhance staff to support the research mission, build and upgrade research facilities and instruments, augment support for student academic success, and retain faculty and staff through additional salary support.

Baker lab IDs rare tuft cells in salivary glands that may prove significant in Sjögren’s disease

October 20, 2023 By Kiefer, Sarah (MU-Student) in Research

Lab of Olga Baker, a Bond LSC researcher and professor of otolaryngology at the University of Missouri. From left to right, Harim Tavares dos Santos, Olga Baker, Kihoon Nam, and Frank Maslow. | Photo by Sarah Kiefer, Bond LSC

By Sarah Kiefer

A digital declutter is a way to get rid of the seemingly endless files of old photos and documents, but when Harim Tavares dos Santos started sorting through computer files from the Baker Lab at Bond LSC, one image stood out and led him down a rabbit hole.

The picture showed tuft cells, a rare type of cell on his screen that seemed to wave hello with their finger-like structures.

“They looked different from other cells, so I looked into it more and I found that they actually had a name, but not much other than the basic research had been done on them,” said Tavares dos Santos – a senior research scientist in the Baker lab at Bond LSC.

Those tuft cells may be an important link in his study of Sjögren’s disease, a chronic autoimmune disease that destroys cells that make saliva and tears. He recently identified these cells in ducts – responsible for expelling saliva – of the submandibular glands across species in mice, pigs and humans using transmission electron microscopy, a process that can magnify a sample up to 2 million times its size.

Tuft cells — named after their tuft-like microvilli — serve as sentries on the surface of organs to detect chemicals then signal immune and nerve cells. In the gut, these specialized epithelial cells can sense chemicals from parasites and microorganisms to alert the body of the invaders. While first found in the intestines, they also line airways, nasal cavities and other hollow organs. For Tavares dos Santos, their presence in salivary glands provides a possible link to Sjögren’s.

Looking like a bottle-shaped base topped with a latex glove, these cells were first discovered in 1956, but have been vastly understudied. They use receptors similar to those that detect sweet and bitter taste to regulate inflammation in several organs, including the intestine.

Tuft cells are currently an enigma in many tissues, leaving more questions than answers for researchers. After establishing their presence in salivary glands across species, Tavares dos Santos wants to pinpoint what they do there. He hypothesizes that tuft cells are involved in Sjögren’s pathogenesis. Still, ongoing studies are being conducted to confirm or refute this notion. Tavares dos Santos recently obtained a NIH K99/R00 grant and a Sjögren’s Foundation grant to work on this project, in which Baker will mentor Tavares dos Santos during the training phase of both of these grants.

“These types of cells were just forgotten in time and there is now a huge gap between the discovery of tuft cells and the first reports of their function,” Tavares dos Santos said. “I hope to work towards closing that gap and determining their specific role in the salivary glands and how that impacts clinical treatments for Sjögren’s patients.”

Harim Tavares dos Santos looks at the fluorescent tuft cells that appear green on the monitor. Identifying how tuft cells work in salivary glands is essential in understanding the causes of Sjögren’s disease. | Photo by Sarah Kiefer, Bond LSC

He wants to understand the molecular, morphological, and functional roles of tuft cells in salivary glands health and disease. Once Tavares dos Santos deciphers the code for the role tuft cells play, he plans to expand this knowledge to other conditions affecting salivary gland function such as irradiated salivary glands from patients treated for head and neck cancers.

But for now, Tavares dos Santos will focus on Sjögren’s.

“This work makes me feel challenged because tuft cells are poorly understood, so everything we discover about the role of tuft cells in salivary glands is new information,” Tavares dos Santos said. “I am excited about the idea that this research could help people in the future.”

Harim Tavares dos Santos published the paper “Tuft cells are present in submandibular glands across species” in the Sage Journal of Histochemistry & Cytochemistry in August 2022.

Harim recently received an NIH K99/R00: Pathway to Independence Award as well as a Sjögren’s Foundation grant that gives him the resources and the support to become a future faculty principal investigator.

Ongoing vaccine projects address 100-year-old disease and others in fight against tick-borne diseases

October 6, 2023 By Kiefer, Sarah (MU-Student) in Research

By Sarah Kiefer

It only takes a quiet walk through the Missouri woods to encounter ticks. As they crawl from the rich vegetation among the bushes and grass onto humans and animals alike, they wreak havoc on their hosts by passing on disease causing bacterial pathogens.

One of those pathogens known to cause a 100-year-old disease is Rocky Mountain Spotted Fever (RMSF). University of Missouri scientist, Roman Ganta, hopes to understand its inner workings to one day develop a vaccine against it.

Like several tick-borne pathogens belong to rickettsial bacteria, such as Ehrlichia Anaplasma, and Rickettsia species that cause severe diseases in various vertebrate animals, including people. Ganta has been investigating and developing vaccines against important tick-borne diseases that cause Anaplasmosis, Ehrlichiosis and RMSF in people, companion animals and agricultural animals.

“We are doing basic research first because it has to be translational, so we cannot continue without first understanding the fundamentals of the root cause of a disease,” said Ganta, a Bond Life Sciences Center principal investigator and McKee endowed professor of veterinary pathobiology. “Then we can apply that understanding to develop prevention methods to make the environment healthier and improve lives.”

RMSF is one of the most dangerous tick-borne diseases and without treatment, it can lead to death in a portion of the infected. RMSF gets its name from the red spots that appear on a patient’s skin due to damaged blood vessels. These spots can swell the arms, legs, face, and body, causing difficulty breathing and other complications. The bacterium Rickettsia rickettsii is primarily transmitted from an infected tick, although person-to-person and animal-to-animal transmission is possible.

Several tick species are known to harbor the pathogen, including the Lone Star tick (Amblyomma americanum) which has widespread distribution in Missouri and several neighboring and southeastern states.

Ganta’s research builds toward vaccines to protect against a number of tick-borne diseases.

The Ganta lab picks apart each individual gene of pathogenic rickettsial bacteria transmitted by ticks in causing diseases to identify whether it is essential for pathogens’ survival in ticks, vertebrate animals, or both.

Ph.D. graduate student Jonathan Ferm (right) prepares a pipette with cultures to inject into a sample while Dominica Genda (left) takes notes on the process. | Photo by Sarah Kiefer, Bond LSC

“We expected that all the genes for the vertebrate host would be equally essential for the tick, but that was not the case,” Ganta said. “Only a small group of genes were identified as equally essential for a pathogen’s growth in a tick which was surprising.”

Armed with this knowledge, the team can build a better defense against tick-borne rickettsial diseases.

“Because we now know what proteins are essential, we can create enhanced strategies for drug and vaccine development in promoting the health of people, companion and agricultural animals,” he said.

National Institutes of Health (NIH) funding helps him work on multiple vector-borne disease vaccine projects such as RMSF, Ehrlichiosis and Anaplasmosis. A vector refers to an organism—often a blood-sucking insect or tick—that carries a pathogen from one animal to another. Those pathogens are responsible in causing diseases like RMSF, Ehrlichiosis, Anaplasmosis, and Lyme disease.

To successfully infect a vertebrate host, the pathogens have developed ways to avoid rejection and hang on to their hosts. The pathogens derive nutrients from the hosts to support their survival. While scientists don’t entirely understand what benefit ticks get out of a pathogen, Ganta looks for clues in how the genes in a pathogen change their protein expression in vertebrate hosts and ticks. He wants to understand the gene expression of pathogens during their growth in ticks and vertebrate hosts so that he can identify what the pathogen needs to survive and use that knowledge to craft a vaccine specific to each pathogen.

Roman Ganta inspects a sample of cultures that is grown in order to generate a pellet that is then put under a microscope for closer observation. | Photo by Sarah Kiefer, Bond LSC

“How the proteins are expressed differently provide us with the whole story of what is essential for a pathogen in a tick and what is essential for it in a vertebrate host. Once we know that, the next step is to see what happens if you take those essential proteins out of those pathogens,” Ganta said. “Do the bacteria die or do they survive and grow differently in one host versus another? That’s what we investigate.”

Ganta has been pursuing this line of research for over 15 years with the continuous NIH grant support that began in 2007. His work on the RMSF vaccine project started as part of a $3.7 million NIH grant in August 2021 when he was a professor at Kansas State University (KSU). He has since continued it after his move to MU in early 2023.

Ganta’s vaccine projects on Ehrlichia and Anaplasma species pathogens started with an additional $3.2 million NIH grant that began in June of 2020 at KSU and has since been transferred to MU. Ganta’s research success has been creation of vaccines that are 100% effective in protecting dogs from the devastating diseases;RMSF and Ehrlichiosis, and Anaplasmosis in cattle. RMSF vaccine results were published in a paper in 2019, while Ehrlichiosis and Anaplasmosis vaccine work were published in 2015 and 2022, but this kind of vaccine research is yet to be extended to humans.

Ganta feels that improving the health of companion and agricultural animals will have a positive impact on the health and well-being of people. Ganta’s current focus is to test how long a vaccine protection will last and if the vaccines protect against infection in all areas of the world where the diseases are widespread.

“If these vaccines don’t protect for a long period of time, what do we do next? We have to find a better solution to extend the immunity, such as offering a booster vaccination or modify the vaccines to offer protection against distinct pathogen strains,” Ganta said.

Ganta’s RMSF vaccine is a whole-cell antigen inactivated vaccine, while Ehrlichiosis and Anaplasmosis vaccines are based on modified live attenuated bacteria. These approaches take the entire “cocktail” of proteins from the bacteria to trigger immune responses in patients without causing diseases.

“What do you do when you go to Alaska in the wintertime? You put on a coat. What do you do when you go to the Caribbean in the summertime? You wear something more comfortable for the hot weather. That process is called adaptation, and pathogens in ticks and vertebrate hosts do the exact same thing, adapting to different host environments” Ganta said.

Because pathogens constantly evolve, the vaccines must be able to handle those changes. Currently, Ganta and his team are fine-tuning vaccine variations for RMSF, so that the vaccine works against different strains of the bacteria and to define the length of protection in animals. Similarly, his team has been investigating and improving the vaccines against Ehrlichiosis and Anaplasmosis.

The team’s active modified live vaccines against tick-borne infections from Ehrlichia and Anaplasma pathogens are also effective in preventing the diseases such as Ganta’s modified live vaccine that has been effective in preventing canine ehrlichiosis and bovine anaplasmosis.

His research with the USDA grant support has been attempting to define pathogenesis with a far-reaching goal to develop a vaccine against a foreign animal tick-borne disease caused by Ehrlichia ruminantium. This pathogen results in heartwater disease in sub-Saharan Africa and parts of the Caribbean in both domestic and wild ruminants and can cause up to 80% fatalities in livestock population if introduced into the U.S. accidentally.

Ganta hopes that his continued vaccine research will one day help minimize several tick-borne diseases impacting people, companion animals and food animals.

The paper, titled “Multiple Ehrlichia chaeffeensis genes critical for persistent infection in a vertebrate host are identified as nonessential for its growth in the tick vector; Amblyomma Americanum” was published in June 2023 in Frontiers in Cellular and Infection Microbiology, detailing the genes that the Roman Ganta lab identified as essential and nonessential for the pathogen’s growth in a tick. The paper on the RMSF vaccine development and efficacy in dogs, titled “Rickettsia rickettsii Whole-Cell Antigens Offer Protection against Rocky Mountain Spotted Fever in the Canine Host” was published in 2019 in the American Society for Microbiology Journals. The work Ganta has done on Ehrlichia and Anaplasama was published in 2015 in the in the American Society for Microbiology Journals titled “Attenuated Mutants of Ehrlichia chaffeensis Induce Protection against Wild-Type Infection Challenge in the Reservoir Host and in an Incidental Host” and 2022 in the Public Library of Science (PLOS) “Targeted mutagenesis in Anaplasma marginale to define virulence and vaccine development against bovine anaplasmosis.”

Singh lab finds new protein that induces the effects of the COVID-19 vaccine and the treatment drug remdesivir

September 13, 2023 By Kiefer, Sarah (MU-Student) in Research, Uncategorized

Kamal Singh (right), a principal investigator at Bond Life Sciences Center, assistant professor in the MU College of Veterinary Medicine, and the director of the Molecular Interactions Core stands next to Saathvik Kannan (left), a senior at Hickman High School and a computer programmer and researcher for the Singh lab. | Photo by Roger Meissen, Bond LSC

By Sarah Kiefer

The spikes that protrude from SARS-CoV-2 present a topography of peaks that drive one MU researcher to ask more questions.

To Kamal Singh, a principal investigator at Bond Life Sciences Center, assistant professor in the MU College of Veterinary Medicine, and the director of the Molecular Interactions Core those spikes are a changing map with every new variant of coronavirus, and they lead his lab to study its constant evolution of mutations and proteins.

The Singh lab recently found an unexpectedly high number of APOBEC-mediated mutations among a patient cohort from South India, who were vaccinated and have taken remdesivir to treat COVID-19. Using data from patients from South India, Saathvik Kannan, a senior at Hickman High School and a computer programmer and researcher for the Singh lab, tracked changes to the virus’ proteins.

“Viruses are known to evolve under pressure, so what’s happening in this case is that antibodies recognize the virus in a cell, and the virus sees that, ‘okay, there is someone to stop me,’ so it makes mutations,” Sing said.

The virus’ genome often alters, by mutating, inserting, or deleting the building blocks within RNA and DNA known as nucleotides, depending upon the pressure that viruses experience. Only some of these sugar-containing nucleotides are mutated, but these small changes can form a new virus variant.

“A few months ago, we didn’t know the reason behind all of these different mutations in patients because we did not look for APOBEC-mediated changes in viral genome,” Singh said.

Kannan found that between October 2022 to January 2023, the mutations among the patient cohort varied between 114 to 83. With that information, he identified 50% of patients who have diabetes and that when they take insulin the APOBEC protein is also induced. This new discovery leads to more questions about those with underlying conditions like diabetes or hypertension, and how they are affected differently by the drug.

“Ideally if a virus were to evolve you would see a linear progression, but you don’t see that here,” Kannan said. “This shows us that APOBEC proteins are likely one of the causes of this evolution in the virus and the makers of these variants.”

When the number of mutations vary significantly, like in the cohort, it re-affirms that the COVID-19 variants evolve independently.

Viruses don’t stop to wait for researchers to find the root of the problem. They constantly change, and in cases where the patients are vaccinated and take remdesivir, the virus evolves by taking advantage of the APOBEC protein.

Singh started down this path of research early on in the pandemic. Through PCR tests — which converts tiny amounts of RNA into DNA then copies it to a measurable level — he learned more about each mutation by comparing new samples to the original viral strain. Until this point, there had only been around 40 identified mutations in the spike protein in the different XBB sub-variant, but Singh’s lab has identified two more. The details have been recently published in The Lancet Journal. The two mutations found in this process, A27S and T747I, were unique to this cohort.

“For the first time we’re able to get more clues on what is actually happening because we were able to compare it to patient samples in the XBB subvariant and we had a wealth of data to work with,” Kannan said.

The Omicron variant yields new mutations constantly — currently at 43 and counting — and presents plenty of opportunity to look for differences. Singh directs his team to comb through variant sequences to identify differences in their genetic code. Soon they begin to identify trends from one month to another.

“The main difference here was that we have high quality patient data this time, from a patient cohort in Southern India, as opposed to getting it from a database,” Singh said. “The patient cohort tells us that the mutations are more than what was reported before.”

From January to June of 2020, Kannan found mutations that were present in one hundred percent of the sequences. When the Alpha Beta variant arrived in November 2020, they immediately knew what the mutated changes were. Their findings were published in the paper, ‘Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India – a cohort study,’ in April 2023 in the Lancet Regional Health – Southeast Asia Journal.

After new variants — such as the XBB sub-variant of Omicron — materialized, Singh’s lab identified existing drugs and new drug compounds that match structural weaknesses presented by mutations.

One way Singh’s lab keeps abreast of new variants is by utilizing the tools they have available to their advantage with in-house programs either in Python or in R programming languages. Their lab can construct non-infectious, virus-like particles that contain all the same characteristics as the virus minus its genome, or its genetic material makeup.

A collaboration between University of Missouri and University of Nebraska Medical Center helped identify the new drug compound, MU-UNMC-2 in addition to the MU-UNMC-1, previously found in late 2021, as potential coronavirus treatments.

Singh and his lab use 3D visualization and computational tools to show the relationship between the mutations and their effect. They combine this knowledge with the 100% vaccinated and remdesivir patient cohort. | Photo by Sarah Kiefer, Bond LSC

Remdesivir, ribavirin, favipiravir, and molnupiravir were among existing drugs that can be used to treat COVID-19 under certain conditions. Remdesivir — previously ineffective as an Ebola virus treatment — initially proved somewhat useful for COVID-19. Molnupavir only showed moderate promise, and the two drugs were approved for emergency use by the FDA for the treatment of COVID-19. Remdesivir now has full FDA approval.

“To address the problem, you have to find the problem. Where is the virus? What can we address? And then we go after it,” Singh said. “My lab was the first one in the world who suggested when the pandemic came that these are a few drugs that can be used and remdesivir was one of them. I’m very proud that I could contribute to human health in that way.”

Singh views two drugs found in 2021 with a collaboration between the University of Missouri and the University of Nebraska Medical Center. The figure shows the two structures of the drugs and how they bind in between the virus and its entry point into the cell. | Photo by Sarah Kiefer, Bond LSC

With knowledge of this new protein in hand, Singh’s lab now is moving forward to focus most of their attention on the APOBEC protein mediated mutations and how underlying health conditions can affect an individual’s reaction to certain drug compounds.

“The virus has been outsmarting us, outfoxing us, until now. As soon as we get something, it changes itself,” Singh said. “That keeps us motivated as we chase it.”

The Singh lab’s research on the XBB sub-variant mutations was published in the paper ‘Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing anitbodies’ in the “Computational and Structural Biotechnology Journal” in June 2021 and their updated findings can be found in the paper ‘Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India – a cohort study,’ published in “The Lancet Regional Health – Southeast Asia Journal” in April 2023.

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.

#IAmScience Torin Hunter

September 1, 2023 By Kiefer, Sarah (MU-Student) in #IAmScience, Uncategorized

By Sarah Kiefer

The hunt for emerging coronavirus variants keeps Torin Hunter busy testing samples from sewer systems across Missouri.

As a part of The Sewershed Surveillance Project, Hunter has spent the last year and a half taking each test tube and carefully filtering the samples to contribute data on how SARS-CoV-2 can be present in our communities.

But Hunter started his journey in virology like many — a student trying to sift through all the different subjects and figuring out what fit him the best. He tried out clinical jobs and considered going into the health professions, but he began to miss the lab and research more than he thought.

“I missed the freedom and the creativity you get from research while still being able to do science and complete it all by yourself. It’s more fun and satisfying to me,” said Hunter, a senior research technician in the Marc Johnson lab at Bond LSC.

Virology, the study of viruses, stuck for Hunter.

“I like the blend of molecular virology and epidemiology here because it is fascinating to see the public health implications of what we are studying,” he said. “Even though our work has focused on coronavirus in the past few years, I would still want to be doing this type of work even if it were involving a different virus.”

As a senior research technician, Hunter enjoys projects where he can think through an experiment and work backward if problems arise. Using his analytical skills, he can determine if the experiment was meant to go in a certain way or if the issues can be boiled down to human errors made along the way.

“Starting an experiment and then getting real results from it that make sense is the most exciting part of my job,” Hunter said. “Knowing that I did it by myself and that I accomplished something I worked hard on is a great feeling.”

Originally from Orange County, California, Hunter moved to Missouri when he was 16 and knew he wanted to attend the University of Missouri not long after that. In high school, he began to take an interest in the inner workings of cells, which is where biochemistry comes into his life.

He went on to earn his bachelor’s degree in health science from Mizzou and his master’s degree in microbiology and cell science from the University of Florida. When Hunter took his first undergraduate class in biochemistry, he became hooked on the subject and its value in a research setting.

“Biochemistry is when everything clicked in the life sciences for me, and it made the most sense to me, but the subject is so broad that I still didn’t know exactly where to go from there.”

Hunter works daily with samples of human waste systems across the state. He extracts viral nucleic acids (such as DNA or RNA) out of the samples using polyethylene glycol or magnetic beads and sends them off to a collaborating lab. The lab then performs digital polymerase chain reaction (dPCR) to quantify, or measure, the viral load of SARS-CoV-2 in the wastewater samples. The process can be compared to a nasal swab coronavirus test, but instead of simply measuring the virus’ presence, the amount of virus in the sample is measured as well.

The amount of each marker is graphed on a chart, and these charts are analyzed and monitored in collaboration with public health officials to compare trends across the state. Hunter finds it interesting to learn about how different viruses cause disease.

“If we can better understand why and how viruses cause harm to people, we can develop more therapeutic or preventative options like vaccines and help a lot of people in the long run,” Hunter said.

Hunter performs these steps often and finds that this type of work takes a certain amount of discipline. He meticulously combs over his notes and studies the details of his experiments and what might have gone wrong in the procedure.

“You go through every possible way that something could go wrong, but if those are still your results, you might just have to go further back in your process or go in a different direction entirely,” Hunter said. “That’s what makes this work so interesting, is that you’re always problem-solving.”

In his time away from the lab, Hunter enjoys playing video games, weightlifting, and cooking to turn his brain off after a day of experimentation.

“It’s important and healthy to have a work-life balance,” Hunter said. “I will often think of new dinner recipes to try and make as my own way of experimenting at home.”

After his research at Bond LSC, he plans to apply for Ph.D. programs this fall to continue his studies in virology. Specifically, he would like to learn more about immune responses to viral infections.

“Everybody has to work, and if you’re going to work hard at something, you might as well do the thing that you enjoy the most,” Hunter said.

#IAmScience Vikranth Chandrasekaran

August 25, 2023 By Kiefer, Sarah (MU-Student) in #IAmScience, Uncategorized

By Sarah Kiefer

With a forceful swing of his badminton racket, Vikranth Chandrasekaran propelled the shuttles across the court. A game with coworkers and friends is the perfect way to wrap up a day in the lab for the postdoctoral fellow. He’s offered to teach his colleagues the strategies of badminton at the University of Missouri Rec Center.

“When I initially embarked on my journey in badminton as a beginner, I received invaluable assistance and guidance from numerous South Korean individuals who graciously taught me the proper techniques,” he said. “Now, I feel compelled to reciprocate this kindness by offering my help to those who aspire to learn badminton.”

As a postdoc in the Bing Stacey lab at Bond LSC, Chandrakaran has the opportunity to help others through soybeans, and his path here started in South Korea with Gary Stacey.

During the joint venture conference between the University of Missouri, USA and Gyeongsang National University, South Korea, Chandrasekaran found Stacey’s research talk fascinating and made him want to visit Bond Life Science center.

“I want to find the answers behind many unknown questions and be the one to make new discoveries,” Chandrasekaran said.

Chandrasekaran is from a land of gold mines: Karnataka, India. Coming from Kolar Gold Fields, he can appreciate searching for the nutrients within our food and his past planted the seed for his future.

“My motivation for what I do comes from my strong determination and passion towards plant science for the betterment of humankind that I have,” Chandrasekaran said. “My childhood aspiration was to achieve the highest degree in the scientific field, a doctoral degree, and with unwavering support from my parents I was able to realize that dream.”

Chandrasekaran deals with soybeans and the macronutrients they provide. Soybeans are an important source of protein for a vegan diet especially, with a single seed consisting of 40% protein and 20% oil. The crop is a leading source for vegetable oil and protein production, providing 60% of global oilseed production and more than 25% of the in food and animal feed worldwide.

Chandrasekaran investigates the phenotypes of the soybean plants and takes care of his plants by doing regular pruning and weeding. | Photo by Sarah Kiefer, Bond LSC

“Engaging with academic theories for research proved to be profoundly challenging because they often neglected the intricate trial-and-error nature inherent in research endeavors,” Chandrasekaran said. “But research entails a myriad of trial-and-error processes, involving a multitude of fine-tuning techniques that extend beyond the scope of conventional academic teachings. These trial-and-error methods lead me to learn more and help me to solve a problem in my research in a more effective way.”

In the Stacey lab he finds the genes responsible for high protein and oil content in order to then edit DNA to increase the amount of protein and oil contained in the plant. Less than 30% of the genes in soybeans and 70% of those in rice have been identified, so Chandrasekaran aims to find more.

“I was first fascinated with research because of the DNA double helix structure and how we analyze things like that,” he said. “I was always focused on the theoretical part of academics, but then all of the sudden I was really curious about the research side as well.”

When he screens the soybean plants for genes, he pays attention to the visible phenotypes, that the plant makes in response to a procedure using fast neutron radiation (ϒ rays or gamma rays), which is often used in cancer patients to treat tumors. For each phenotype there are many genes competing to express themselves, so Chandrasekaran deciphers which traits are likely distinct, or abnormal phenotypes, when compared to normal soybean plant.

Chandrasekaran’s soybean plants are kept at Bradford Research Farm, the largest concentration of plots dedicated to research in Missouri, with 591 acres of land. He regularly goes to weed and take care of the plants, which are uneven in height and thickness because they are mutant plants. | Photo by Sarah Kiefer, Bond LSC

He finds a calmness in this type of work much like the tranquil feeling he experiences when he travels to places such as the Rocky Mountains.

“The drive was about 13 hours and that scared me at first,” he said. “But when I was driving, I was calm and got to experience for the first-time incredibly beautiful scenery that I had never seen before which made the drive worth it.”

He also frequently makes the 405-mile trip to Chicago to visit his childhood friend and their family each month. A long drive gives Chandrasekaran time to think and makes him more motivated about his work when he returns.

“Taking short breaks from continuous lab and field work helps me to feel happier, have more energy and focus more on my research,” Chandrasekaran said.

He uses travelling and a game of badminton with coworkers and friends to wrap up a day in the lab or take time to think on the road he is paving to making scientific discoveries. He hopes to continue his work in the field and secure a position as a crop scientist or to start a research lab of his own one day.

Kranawetter receives USDA fellowship to explore plant border cells

August 17, 2023 By Kiefer, Sarah (MU-Student) in Research, Uncategorized

Clayton Kranawetter, a postdoctoral fellow in the Lloyd Sumner lab at Bond LSC, recently received a USDA National Institutes of Food and Agriculture Postdoctoral Research fellowship in which he uses this mass spectrometry machine to study the significance of plant border cells. | photo by Sarah Kiefer, Bond LSC

By Sarah Kiefer | Bond LSC

Some of the most fascinating things in science happen at the border where one organism interacts with its environment.

That’s the case with root border cells, and Clayton Kranawetter is one individual exploring this frontier.

Kranawetter recently received a $223,000, two-year USDA National Institutes of Food and Agriculture Postdoctoral Research fellowship for his project on this group of cells. This fellowship is a part of a larger $12 million investment in multiple institutions by the USDA to expand research in the area of agricultural microbiomes. The University of Missouri is among 17 research institutions to receive funding.

“I’m still shocked by receiving the award. I was already having a good day when I received my award notice. I found a good parking spot in the garage and a quarter on the sidewalk, but then I got the email” said the postdoctoral fellow in the Lloyd Sumner lab at Bond Life Sciences Center. “I thought it was a mistake at first and then I realized, ‘oh, this is real.’”

This fellowship will sustain his work in an influential way as he dives into the secreted metabolites and mechanisms of isolated border cells and their impact on rhizosphere dynamics.

Metabolites are small molecules made or used when a cell breaks down food, reacts to certain signals or completes other essential processes. Some metabolites, such as glucose, are part of an organism’s central or primary metabolism and its basic life functions. Other metabolites, such as secondary or specialized metabolites, are less essential to sustaining life but no less integral as they help with plant defense responses. Identifying these metabolites can help researchers predict how plants will react to various biotic and abiotic conditions, such as high light, stress from salt, symbiotic interactions, and defense against pathogens.

“I love science because everything is a puzzle,” Kranawetter said. “Sometimes the puzzle is a struggle to put together and can look quite different from what you expected, but after everything is complete, it is always rewarding and empowering to see how the pieces fit together.”

Kranawetter’s work focuses on root border cells, which are vital to plant root health. These cells arise from the root epidermis, where the cell wall breaks down and the cells are physically released from the root but still surround the root tips. Border cells are held in place through a water-soluble, complex secreted matrix consisting of a polysaccharide mucilage, comprised of DNA, proteins, and metabolites. As their encasing material is water soluble, upon contact with water they wash away but are rapidly replaced within 24 hours after their removal. After border cells separate from the root tip, Kranawetter conducts large scale genetic reprogramming to divert most of their resources to secretion and specialized metabolism. In doing so, they serve a protective role against infection and environmental stress, but the scope of their functions is far from fully explored.

“Border cells are still very niche, and we don’t fully understand how they’re contributing yet, but we’re starting to see that they are more major players in the rhizosphere than we thought initially,” Kranawetter said.

Root border cells appear across most plant species. They are known influencers of dynamics within the rhizosphere — the layer of soil that is in direct contact with root secretions — but there are still a large number of unknowns about them.

Kranawetter’s previous work dealt with metabolites, or small molecules, and their differential accumulation in root tissues. He collected root border cells and separated individual root tissue types to create a metabolite atlas based on the Arabidopsis eFP browser – a computer program that shows the relative intensity of metabolites by tissue type in a heatmap context. This project builds on his work to further identify the molecules border cells secrete and how they mediate plant-microbe interactions.

Although this project does not directly correlate with his current research in the Sumner lab focused on differential metabolite accumulation in cultivated elderberry plants, it will allow Kranawetter to stay in plant tissue research, build on the foundational mass spectrometry knowledge he accumulated during his Ph.D. and incorporate microbiological techniques to border cells.

“Working on elderberry plants was a good chance for me to start a different project in a distinct plant system, which has been nice,” he said. “And this fellowship will be a great opportunity to apply my current research skills and knowledge base while also developing new abilities.”

For the NIFA fellowship, Kranawetter generated a project narrative, abstract, budget, a logic model, references, and a data management plan, among many other materials. He also utilized a three-member administrative board to support and look over the project in order to assist and give feedback each step of the way.

“This will be a project for me to get out of my comfort zone and gain new expertise compared to what I have done in the lab previously,” Kranawetter said. “It’s nice to have a different perspective when, instead of having a bunch of giant elderberry bushes in the greenhouse, I’m working with three-day-old seedlings.”

The fellowship allots Kranawetter the resources and time he needs to monitor border cell metabolite secretions and their methods of secretion. Kranawetter also observes the bioactivities within an organism living in symbiosis with its pathogens, the microorganisms that cause disease.

“The field of mass spectrometry allows me to apply novel technologies and software systems, while plant sciences allow me to explore the vast diversity of compounds that plants naturally produce,” Kranawetter said.

Kranawetter applies what he knows about border cells in experiments on Medicago truncatula — a close relative to alfalfa — and observes how border cells use their secretions to affect the rhizosphere.

“The question we’re aiming to answer is how are these secretions going into the environment and what role are they playing,” Kranawetter said. “I wanted to get back to my roots with this because as a mostly technical lab, I haven’t done a lot of molecular biology in some instances.”

Kranawetter first removes the seed coat from M. truncatula and sterilizes them in order to protect them from bacterial or fungi contaminants. Next, he places the seeds on a petri dish containing water agar overlaid with sterile filter paper so that the roots remain on top, as opposed to normal methods of plating directly on top of the agar. This ensures that the roots do not penetrate the agar, where border cells would be lost. Although some cells are still lost due to the minimal contact with the filter paper, most remain for later harvest. The final step is to dip the roots in water and harvest border cells — ones that freely come away from their root system — for closer investigation.

As part of his fellowship, Kranawetter is probing for transcripts and proteins associated with metabolite secretion. His results will help determine how border cells affect their environment through their secretions. Kranawetter’s interest in this field stems from his love of plants and technology, both of which he uses in his daily lab work.

“One of the major benefits of being in the Sumner lab is that we’re getting to use very sophisticated instrumentation and applying it to something that we probably would not have been able to examine otherwise,” Kranawetter said.

Kranawetter’s fellowship lasts 2 years, so he hopes this exploration expands our understanding of border cell interactions with the rhizosphere.

“I love this type of research because I get to do a lot of different things! I grow plants, work at the bench, and also use cutting edge instrumentation,” Kranawetter said. “Being able to work in such a diverse manner makes me feel empowered as a scientist.”

Find details on Kranawetter’s fellowship at the USDA NIFA website.

The U.S. Department of Agriculture’s National Institute of Food and Agriculture (NIFA) announced an investment of $12 Million to Advance Research in Agricultural Microbiomes. Microbiome research is critical for improving agricultural productivity, sustainability of agricultural ecosystems, safety of the food supply, carbon sequestration in agricultural systems, and meeting the challenge of feeding a rapidly growing world population. Research supported by the Agricultural Microbiomes in Plant Systems and Natural Resources program area priority within the Agriculture and Food Research Initiative (AFRI) will help fill major knowledge gaps in characterizing agricultural microbiomes and microbiome functions across agricultural production systems, and natural resources through crosscutting projects. AFRI is the nation’s flagship competitive grants program for food and agricultural sciences.

#IAmScience Alexandra Diller

August 9, 2023 By Kiefer, Sarah (MU-Student) in #IAmScience, Uncategorized

By Sarah Kiefer

Alexandra Diller jumped off a cliff, in a sense.

Instead of taking on more clear and straightforward science, she dove into vessel regeneration and never looked back as she works on the burning question, ‘can muscles regenerate in the absence of blood vessels and vice versa?’

“Knowing how vessels grow back can one day improve treatment options and help someone who has suffered a traumatic muscle injury and I really like contributing to that, but at the same time I want to know and do more right now” said the D Cornelison lab member.

Diller studies the interaction between regenerating muscle and blood vessels after a traumatic muscle injury and the role of ephrin-B2 (an essential protein for blood vessel formation during development) in blood vessel regeneration and when it is no longer necessary for development. While she studies these questions, she sees the connections in friends, colleagues and hobbies.

“One of my best friends works in the NICU [Neonatal Intensive Care Unit] as a social worker, and it can be hard for us to find common ground in terms of our careers,” Diller said, “but I started working on development and she was like ‘oh we see that in the babies too’ and then all of a sudden we had this crazy crossover between social work and mouse development.”

Recognizing these similarities lets Diller find new research skills and learn from others outside the field.

“It’s crazy how I can talk to an ecologist friend of mine who’s studying something completely different from me, and then they have an idea or say ‘have you tried this,’” she said. “Sometimes that leads to inspiration to help deal with a setback.”

Balance outside work helps with setbacks and obstacles within her research project. Diller tends to spend her free time on activities that prioritize her health, her relationships with her husband and friends, and her dog, Harry. She takes her dog to agility classes, but finds Harry is more in tune with the program than she is.

“I’m constantly being corrected by the trainers because you’re not supposed to step in front of your dog, and Harry just stands there and looks at me like ‘How do you not get this mom?’ But it’s a fun activity for us to do together, so I continue doing it,” Diller said. HIIT and resistance training classes bring more balance and a chance to interact with those outside the research field.

While Diller’s hobbies come in waves, her love for research persists as she expands her work in the realm of muscle regeneration.

Currently, the Cornelison lab is using conditional knockouts—a technique used to eliminate or delete specific genes from the mouse’s DNA—and pharmacological methods to inhibit angiogenesis – the process through which new blood vessels form—to study the impact impaired blood vessel regeneration has on muscle regeneration. The team looks at hints within the vessels and vessel network, such as new growth (i.e., tip cells), vessel dilation, vessel branching, as well as other structural deformities such as anastomoses (i.e., a connection between blood vessels). But Diller is always striving for more with her work.

Resilience is key when often each new discovery raises more questions about how vessels regenerate.

“As a grad student it’s really important to have coping mechanisms for the level of stress that you go through,” Diller said. “When something fails, being able to take a step back and stop thinking about it helps a lot. And once you’ve calmed down, the best way to deal with it is by talking to the people around you.”

Diller recently graduated from the University of Missouri and has accepted an NIH fellowship at the University of Florida to study the effect of hyperbaric oxygen treatment on vessel regeneration in the diaphragm in a spinal cord injury model. Diller is excited to work specifically on diaphragm recovery options and take this patient-focused opportunity.

“Science is for everyone, which sounds cliché, but I think that there is an aspect of science that almost everyone can relate to. It’s not always going to be the same thing for each person, and I like how science connects people through their differences.”

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