I am science because I want to breed more new elite Brassica vegetable varieties and make people more healthy.
Twenty-two years is a long time to focus on a single vegetable, but Yuxiang Yuan has done just that with Chinese cabbage.
That focus has led her away from her normal life in China to the Chris Pires lab at Bond LSC for a year-long project that’s winding to an end.
After a 20-plus hour flight from China and over 7,000 miles of traveling, Yuxiang Yuan arrived here, excited for a new adventure and the opportunity to improve a staple vegetable for Asia.
Yuan was awarded a fellowship from the International Cultivation of Henan Advanced Talents with the ambition of using hybridizing Chinese cabbage to be more disease resistant. She has been crossing the genes of Chinese cabbage with rutabaga, and, with the help of the Pires lab, has found four clubroot resistant accessions of rutabaga and four susceptible accessions of rutabaga. An accession is a group of related plant material from a single species which is collected at one time in an attempt to capture the diversity present in a given population of plants.
Many Americans probably don’t often think of Chinese cabbage, but for China, the cultivation and yield rank it as the most important vegetable to the economy. Clubroot is a devastating disease to Chinese cabbage and other Brassica crops. In 28 provinces in China, this disease hit cabbage, resulting in 20-90 percent yield loss. Yuan has made it her life’s mission to make cabbage more resistant to the disease, and she said she’s proud of the progress she’s made over the past year.
“In China, I am a research professor,” Yuan said. “Most of the time, I will go to the field to observe my genetic materials and try to breed new varieties more quickly. Here, I am learning new techniques and teaching students in Pires lab. I take part in routine lab management and in a lot of symposium workshops and seminars. I really love Pires’ lab meeting every week.”
You might think Yuan would tire of Chinese cabbage after all that time, but she still loves and values what she gets to accomplish. She said from her undergraduate degree to now, it’s always been about vegetables.
“Science can change everything,” Yuan said, hopeful to make such an important vegetable more stable for millions of people.
One of her favorite things about being at the Bond LSC is the new methods she’s been able to implement in her research. She said with CRISPR and other technologies, scientists can breed vegetables faster and more efficiently. She’s also really enjoyed working with the Pires lab and said the community in this building has been welcoming and friendly.
“I leave in November, and I will miss the people and the dynamic atmosphere here,” she said. “When I first came, I could barely speak English. After almost one year visiting, I have improved a lot.”
Science inspires Yuan to ask tough questions, seek answers and, hopefully, make the world a healthier, happier place through genetic breeding. She may leave next month, but her legacy will live on through the relationships she’s built and the international collaboration she’s helped create.
“I really love the atmosphere in this building, there is inclusive equality and diversity,” she said. “After I return to China, I will continue our collaboration between our institution and MU. I think that one may go quickly, but a team can go further.”
The complex title of the new painting in Bond LSC represents the nuance of its meaning.
By Danielle Pycior | Bond LSC
It appears to simply showcase a spectrum of beautiful colors, but there is much more than meets the eye to the painting above the plant wall by Monsanto Auditorium in Bond Life Sciences Center. Its creative expression is the work of local artist Kerry Hirth and has a particularly unique provenance.
Dean Bergstrom approached Hirth one day when she was in the administrative offices hanging some of her paintings as part of a program where the Columbia Art League loans out artwork to offices for exposure and sale. He walked her down to the living wall, pointed above it and said, we need something to fill that space, will you do it?
This led to the art piece that hangs above the living wall, which is the largest and most challenging work that Hirth has ever created. While she is proud of the outcome, she said she’ll never create something that large again.
Hirth had to plan for a variety of things such as discoloration of the wood board from the pastels, the scalability of her art onto something much larger than normal, exposure to dust and the test of time, among other things, which made the project the challenge of a career.
“It took a long time – there were some things I couldn’t control,” she said. “The epic nature of planning the materials and the execution of meeting a specific end result was challenging.”
After months of preparation and planning on her end and with Bond LSC’s facility staff, she finally began to paint the real deal. Equipped with her hazmat suit, her facemask, an endless supply of gloves that built up over time and the large wooden board, she took creative determination to an entirely new level.
“The project was like mental torture,” she said. “When you’re an artist sometimes physical exhaustion isn’t a thing. If you have the impulse to do something, then you have to do it. I wanted to make a really large painting and I did.”
Hirth is a member of the American Association for the Advancement of Science, and received both her undergraduate and graduate degrees in Philosophy. She now teaches ethics at Moberly Community College along with producing art. She’s a woman with many interests, which only aids in the complexity of meaning in her work. She said her work isn’t meant to be socially or politically charged but is meant to stir the imagination.
In 2007 when Hirth and her husband moved to Chicago, inspiration struck. She recalls he had a fantastic office with a nice view and spent a great deal of time there. So, she decided to create an art piece to bring some color to his day. For something to hang in the spot she imagined, it would have to be long and thin, so she went to the store and bought the supplies. Little did she know that would be the beginning of a career in art.
Around that time, Hirth found out she had synesthesia, a condition where one of the senses is simultaneously perceived with another. In her case, she sees color attached to sound, more specifically music.
“I wanted something that was meaningful in that space,” she said. “For whatever reason, I used that paper, started from left to right, and began to paint in the colors of music. It happened to be a Bach piece.”
Growing up playing piano and drawing with pastels, this project for her husband’s office brought two of her loves together in a transformative way. To others, it seems incomprehensible to associate a complex musical composition with such specific colors, but to Hirth, things are much clearer. Her brain sees a reality that most people can’t imagine.
“Because the experience is so consistent with harmony and color, that’s how I can create a pattern,” she said, pointing to the horizon in the distance. She said it’s just like the pattern of a horizon that stretches from bottom to top, she naturally sees certain colors from left to right when hearing a musical composition.
Though Hirth didn’t discover this specific form of art until later on in her life, she’s always had an impulse to create things, and said it isn’t about casually following desire, but about being pulled to do something. After that first painting, she had to create more.
“I was always aware of how I was different, but I couldn’t before express it in a way that was interpretable to people, and evidently now I can,” she said.
The painting has many more depths than just the color she sees through Sonata in E Major K162 by Domenico Scarlatti. She also connects the left to right color scheme to the first section of The Wanderings of Oisin by Yeats.
Hirth had previously collaborated with a composer on the poem to create art for a previous show. This amounted to an acquaintance with the piece that was hard to shake. She says it worked its way into her everyday thoughts for months and the colors associated with the epic poem were also colors she saw in that composition. She chose the two for the painting because they combined together on so many meaningful levels. She said the epic poem is something bigger than herself; it simply amplifies the importance of the work.
“In the story, Oisin is a mortal king who gets taken by an immortal woman to her home in the Irish Isles,” she said. “It’s about the three different islands that they visit throughout his journey and his return back to human lands.”
The colors in the painting represent the journey that Oisin takes throughout the story. It represents a narrative, the deeper metaphors within that narrative and a complex musical composition as well. What can easily be taken as a pallet of colors up on a wall, is in reality a painting with more levels than any of us could ever intuitively understand.
“The painting itself is divided into three parts,” Hirth said. “The first part is water, the second part is land and the third part is sky.”
Hirth thought and planned for months to help create the perfect symbol for not only the living wall but for the Bond Life Sciences Center. Though it was the toughest project she’s worked on so far, she’s proud of the outcome.
The artwork Hirth created can be seen outside of Monsanto Auditorium above the plant wall. Minus the cost of supplies, Hirth graciously donated the piece to Bond LSC to inspire our scientists, students and visitors.
Researchers from MU, the University of Maryland and the Pacific Northwest National Laboratory are building a microscope that doesn’t yet exist.
By Mariah Cox | Bond LSC
Tiny neon dots speckle a black backdrop – and no, this isn’t a Hasbro Lite Brite. Rather, these fluorescent dots indicate something about plants that scientists research and help them see the genes, traits and molecules they study amid thousands of possibilities.
To help in seeing that, a new imaging microscope will allow researchers to better pinpoint molecular interactions in plants they have a hard time highlighting to overcome the obstacle plant scientists face with wavelengths of light they can’t necessarily see.
“When you think about imaging, you think about what you can see with your eyes. But, there are a whole variety of other things you can image that aren’t visible to the human eye,” said Gary Stacey, a Bond Life Sciences Center principal investigator who is working to help develop a new microscope technology to view fluorescent quantum dot markers beyond the range of visible light, into the infrared spectrum.
Stacey, along with collaborators from the University of Maryland and the Pacific Northwest National Laboratory (PNNL), was awarded a combined $2.25 million grant from the Department of Energy (DOE) to develop a novel microscope for ‘multiplexed super-resolution fluorescence imaging in plants.’
The call for the development of this new imaging hardware was borne out of the need for a more precise measurement of enzyme function, tracking of metabolic pathways and monitoring the transport of materials and signaling processes within and among cells in plants. Right now, the emission spectrum of plant pigments limits the usefulness of and the number of fluorescent colors that can be detected in a single experiment.
Stacey and his collaborators were one of six groups to be chosen for a total $13.5 million investment from the DOE for new bioimaging approaches. For bioenergy, using quantum dots in combination with other novel technologies could enhance imaging techniques to allow scientists new ways to re-engineer plants and microbes for bioenergy conservation and production.
Quantum dots are small particles that are only a few nanometers in size, one nanometer equals one billionth of a meter, and are used as fluorescent biological labels in cells. These labels can be tagged to particular molecules, cell parts or genes of interest to a researcher.
“Think about [fluorescence] as a black light. If you have a room that’s completely dark with fluorescent paint on the wall and you turn on a black light, then you will be able to see where the paint is on the wall,” Stacey said. “It’s the same concept for quantum dots. One application is localizing where a virus is or label it and watch it move into a cell to try to understand the mechanism by which it moves.”
However, the mechanics behind quantum dots don’t make it simple. When exciting a single molecule, it will fluoresce and emit light but will do so in a diffuse pattern. This makes it difficult to see the molecule itself.
Additionally, plants absorb 490-700nm of light — essentially covers the entire visible range of light — allowing them to photosynthesize. As a result of absorbing these wavelengths of light, they also auto fluoresce, which is natural emission of light by structures inside plants cells such as chloroplasts.
The problem, then, is that viruses labeled with fluorescent probes in leaves are difficult to see because of the natural fluorescent glow coming from the plant.
For Stacey and his collaborators, the idea is to go beyond the visible light spectrum and use infrared light, which is above the visible light spectrum. Infrared light is most commonly known for its use in heat lamps.
“With infrared light, there would be no autofluorescence and so when you shine infrared light on a leaf, it would appear black,” Stacey said.” If you shine an infrared light on a fluorescent molecule, it would emit light and show up against a black background, making it very easy to see.”
The problem, though, is being able to distinguish one fluorescent molecule from another when they are close together. Because the researchers will be using infrared light, which has a longer wavelength, the imaging resolution decreases.
To get around that obstacle, the researchers will be using super-resolution microscopy to compensate for the resolution loss. The use of this technology will allow them to pinpoint the center of the fluorescence.
“It should be a big breakthrough. We would be able to look at single molecules interacting against a black background without any interference from autofluorescence,” Stacey said.
Stacey’s collaborators each contribute to the project in their unique way.
Zeev Rosenzweig from the University of Maryland, who is an expert in quantum dots, will be making the dots and labeling them with probes that absorb infrared light. Galya Orr from the Environmental Molecular Sciences Laboratory (EMSL), PNNL, in Richmond, Washington, has expertise in fluorescent microscopy and she, and her colleagues, will build the microscope.
An attractive part of submitting a proposal for the grant is the microscope’s prospect of being used as part of the EMSL user facility, which will ultimately allow researchers from all over the world to use the microscope when fully developed.
The researchers are excited to begin work on this project because they’re building a microscope that doesn’t yet exist. The microscope will expand the capabilities of researchers all over the world.
Stacey is appreciative that he gets to work with researchers from multiple disciplines. Namely, because he learns more about science from the expertise of others.
“That’s what makes it exciting because you’re constantly learning. The great thing about science is that you’re learning every day. It’s nice to get into these new areas especially where you don’t feel comfortable and learn new stuff,” Stacey said.
This work is funded by the Department of Energy for innovating new bioimaging approaches for bioenergy. The grant is split among the collaborators at the University of Maryland, University of Missouri and the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory. Specifically, $1.5 mil. is to be used by researchers at the University of Maryland and the University of Missouri and $750,000 by researchers at EMSL.
#IAmScience because I get to spend the rest of my career being curious and creative, answering challenging questions, and making my small contribution to our collective body of knowledge.
What does competitive swimming and cancer research have in common? For Kimberly Jasmer, the intense world of competitive swimming has guided her towards obtaining her Ph.D. and studying cancer at the University of Missouri.
Learning to swim was imperative for a girl growing up on the coast in North Bend, Oregon, and she fell in love with the water. That love led to a competitive swimming career that began at the age of nine and continued for 16 years, through the third year of her Ph.D. program at MU.
But Jasmer was set on conducting cancer research since high school after her grandmother contracted breast cancer twice throughout her life.
While an undergraduate at the University of Washington in Seattle, Jasmer visited MU for a swim meet. The trip also presented her with the opportunity to speak with Steve Alexander from the Division of Biological Sciences.
“I came out here for a swim meet and set up an appointment with Dr. Alexander and he was very confused why this random swimmer from Washington wanted to meet with him. We ended up having a really great conversation and I applied to graduate school here,” said Jasmer. “Mizzou provided me the ability to do the research I was interested in and also continue my swimming career and it was one of the few places that I could do both of those things.”
Now, 10 years later after starting her program at MU, Jasmer has earned her Ph.D. in Biological Sciences and is three years into her post-doc in the Petris and Weisman labs.
During her time at MU, her research has evolved, but it always ties back to cancer research in some way. For her Ph.D., Jasmer studied a specific enzyme, Heme oxygenase 1, in the body that has the capability to promote tumor growth including melanoma if overproduced.
“Heme oxygenase 1 is considered a protective enzyme but too much can promote cancer,” said Jasmer. “You need enough to protect yourself from DNA damage caused by oxidative stress but not so much that it can lead to other unintended consequences, such as melanoma.”
After, she began her post-doc in the Weisman lab researching Sjögren’s syndrome — an autoimmune disease affecting the salivary and lacrimal glands ability to produce saliva and tears that carries with it an increased risk of developing lymphoma — she has honed in on looking for drugs that inhibit inflammation in the salivary glands to improve saliva flow and minimize the risk of lymphoma development.
Looking to the future, Jasmer has applied for a National Institutes of Health (NIH) grant that would extend her post-doc for one to two years and provide funding for the first three years of a faculty position. The grant would allow Jasmer to begin her own research on finding a radioprotective therapy, which would shield patients with head and neck cancers from the unintended consequences of radiotherapy. This research is connected to her current work on Sjögren’s syndrome because radiation can cause the inability to salivate and produce tears.
This research hits close to home because her uncle suffered from a tumor in his nasal cavity. The radiation he received caused him to lose the ability to produce tears and taste most foods. “I’ve seen the effects of radiation firsthand, and it’s hard for him that he can’t taste anything anymore,” Jasmer said.
Jasmer’s focus and intensity extends to all the goals throughout her life. In her swimming career, Jasmer made it to the national championships and qualified as an All-American for three years swimming at the college level. Additionally, she qualified for the 2008 and 2012 Olympic trials in Omaha, Nebraska.
Although she didn’t qualify for the Olympic team in 2008, she was determined to make a comeback in 2012. Before the 2012 trials, she tore her labrum but was able to recover within a year and qualified again. While not making it past the trials for the second time, Jasmer was proud of all she was able to accomplish within her swimming career.
After her second round at the Olympic trials, she decided to take a step back from swimming. After her time on the MU swim team, she hadn’t returned to the Mizzou swim deck since 2012 until last week.
“Before, swimming reminded me of the disappointment because my career hadn’t turned out as I planned,” said Jasmer. “Now it takes me back to the happy enjoyment of being in the water. When I went swimming last week, it reminded me of what I loved, which is being in the water.”
Now, as a mom, Jasmer hopes her daughter finds passion in an activity as much as she found in swimming.
“I took her to mommy-and-me swim lessons this past spring. I want her to know how to swim and be safe, but I don’t know that I care if she swims or not,” said Jasmer. “My parents had no knowledge of swimming and I think it was fun for them to learn a completely whole new world. So, if she decides that she wants to do an activity that I know nothing about, I just hope she finds something that she’s passionate about.”
Aside from swimming and research, Jasmer serves as the chair of the MU post-doc association board.
“I’m passionate about helping other people develop their own transferable skills they’ll need for their career because it’s easy to just end up doing research and not develop the rest of the skill set needed,” said Jasmer.
She also loves exercising through CrossFit and lifting weights as well as spending her time outdoors, hiking, camping and going on float trips with her friends. She has even taken her daughter Sofie hiking with her in Whistler.
Hollywood cinema stereotypes leave us with a false vision of voracious piranhas that swim in packs and readily attack beachgoers with their sharp teeth and strong jaws.
This simply isn’t true, but their feeding habits are of particular interest to researchers because they can endure long periods of prey shortages and starvation, and scientists are starting to look at the genes behind that advantage.
Bond Life Science Center primary investigator Wes Warren brought his extensive knowledge of genome analysis to a research project with collaborators from Germany and Canada who looked at the genetic expression of the red-bellied piranha under fasting and well-fed diets.
Most fish are faced with short to long-term periods of starvation throughout their lifetime, which cause changes in behavior and the biochemistry of the fish. While piranhas do swim in schools, their feeding habits are much less horror-movie-like than popular culture suggests.
When feeding, piranhas travel in groups of 20-30 and tend to ambush prey in aquatic vegetation, forage the ocean floor for vegetation or invertebrates and opportunistically prey on sick or injured fish. Only rarely have “feeding frenzy” attacks occurred in which piranhas have fed on larger mammals.
But what is it in their genes that could lead to aggressive feeding behavior? The researchers were keen to discover the association of genes which drive aggressiveness and feeding behaviors.
More specifically, the researchers assigned the genes to biological pathways — interactions among molecules that lead to a change in a cell — to try to correlate the genes to certain evolutionary adaptations.
Biological pathways can be thought about in terms of a control room. Environmental cues have the ability to trigger pathway activation, turn genes on or off in the process, cause a cell to move or lead to biological changes within cells. Further, if a particular animal has a more active pathway, it may take much less to turn it on, so in the case of a piranha, it might be much easier to slow their metabolism or turn on a voracious feeding habit.
“For example, if we a say that piranhas have certain genes that appear to be under natural selection and they’re enriched for pathways in the metabolism, we could speculate the piranha lineage has developed some specific amino acid changes to this particular protein which we know is involved in metabolism that helps them deal with longer periods of starvation,” Warren said.
Before beginning research on piranhas, Warren was awarded a National Institutes of Health (NIH) grant to create genome assemblies of various aquatic species. The sequences of these genomes can even help the scientific community link the traits seen in these fish to human diseases.
Warren’s collaborators in Germany and Canada were particularly interested in studying the red-bellied piranha that inhabits neotropical freshwater rivers of northeastern Brazil and in the Paraguay and Parana basins. Previous research on this fish focused on dietary habits and social feeding behavior, but none had looked at the gene regulatory response during periods of food deprivation.
“This gene expression study is the first of its kind in piranhas and provides new information on changes in the genome under caloric restriction,” Warren said. “In particular, it provides evidence for the upregulation of genes involved in metabolism, suggesting an increased utilization of storage fuels and brain energy. The outcome in the piranha is consistent with that seen in other fish species.”
A database of pathways that represent common properties of a particular signaling module in cells helps the researchers link genes to behavior to see if they are enriched, such as a glucose metabolism pathway. From there, researchers can assess whether there is a similar biological process in humans.
“It’s possible to have these delayed periods of feeding where the liver could be adapting to that type of metabolism, and we’re always interested in trying to find unique angles to understand metabolism,” Warren said. “There are lots of metabolism-related diseases in humans, such as diabetes, so the goal is to understand if there’s any kind of evolutionary conservation of some of these pathways and how they respond to extremes in diet.”
The comparative process of discovery is indirect, but scientists have shown repeatedly that there is an evolutionarily conserved response to various stimuli in the environment. Warren says that it’s hard to make a sound biological inference by associating pathways of biological functions in other species, but scientists can use tactics to see enriched adaptations in species over what you would expect to see by chance.
“With the limited number of piranha samples we had for evaluation, we need to follow up these experiments through other types of validation to see if these genes are really driving the traits in piranhas. It’s always interesting to speculate about the linkage of those genes in the piranha driving the trait we examined, but it’s very challenging to prove without some kind of functional experiment,” Warren said.
This research was published in the journal “Genome Biology Evolution” in July 2019 and was funded by Deutsche Forschungsgemeinschaft, Julius-Maximilians-Universität Würzburg, the M.S.I. Foundation, the National Institutes of Health and the Natural Sciences and Engineering Research Council of Canada.
#IAmScience because science allows people to find their own creativity through the art of research.
Every Friday afternoon, the Pires lab can be found in the greenhouse washing pots and cleaning up, and while this could easily be seen as a mundane part of the week, Liz Countee sees it as an opportunity to joke around and enjoy the company of her awesome team.
“I love being surrounded by so many other people that are extremely intelligent and passionate,” she said. “It’s such a great group of people and it’s more than a place to work and do research, it’s a community in itself.”
Countee, an undergrad studying biochemistry, has been in the Pires lab for a year and a half now and has really cherished the experience. Recently, she has been working on coding genome-wide association studies. She said what used to be a foreign concept to her has become an opportunity to grow and progress in new areas. Her mentor and labmates have helped push her in a positive direction throughout her time in the lab, and she loves that there’s always someone looking out for her.
“I’ve gained confidence in being a researcher and my abilities to learn new things even though they may be out of the realm of what I’m used to,” she said.
Though some projects she’s worked on in the lab have been an intellectual reach for her, she’s learned that taking that leap into something new, even if she fails at first, is one of the most beneficial things one can do in life. In research, a lot of things don’t work out, so getting used to multiple tries has been one of the biggest and most beneficial challenges she’s experienced in the lab.
“I enjoy the wider applications of research,” she said. “Of course what I’m doing seems like such a small part, but it can help general plant breeding programs or crop development, and so it becomes bigger. It makes me feel like my little part is making a difference because in the end when it comes together it’ll be one successful product that can benefit a lot of people.”
In May, Countee will receive her undergraduate degree and move on to a master’s program in the fall. After a summer of travel and enjoying those she loves, she plans to dive into a two-year program to become a genetic counselor. Her hope is to one day educate and counsel people on testing, treatment, genetic history and so on. Though she’s excited about her future career, she isn’t quite ready to move on just yet.
“If I had gone to a different university I would not have had such a great experience, and here I’ve really come into myself, and I realize now what I care about and what type of person I am. I’m really grateful to have been here.”
More than anything, she’s grateful for her time at Mizzou and in the Pires lab. She said it’s become more than just a job to her and she values the community she gets to experience.
Broccoli, cauliflower, kale and cabbage all make up an important part of the food system and provide the nutrients we need to stay healthy—yet, there is still much that researchers don’t know about the genetic structure and the ancestral history of Brassicaceae, the mustard and cabbage family.
Hong An, a postdoctoral fellow in Chris Pires lab, has spent the past three years mapping the genetic history of canola seeds, which are in the Brassicaceae family, to find when and where different variations of the vegetables have occurred. Through this research, An can find the timeline of the formation of the vegetables and estimate how they got from one part of the earth to another.
“Canola oil is ranked the second in the world in oil production following soybean oil which makes it a very important agricultural crop,” said An. “Through my research, I’m trying to find specific genes that will help breeders make batter canola oil. “
An can use this research to understand the genes that make up the different breeds of canola seeds around the world. These findings can help researchers modify plants to improve the quality of the oil and optimize the growing of the plant altogether.
Additionally, An studies two subspecies of the canola species, which are rutabaga and Siberian kale, to improve worldwide breeding of these crops.
“I want to find a gene that can improve rutabaga and kale to make them more nutritious and tastier. Rutabaga already tastes good, but kale is bitter, so we want to find the genes in rutabaga that make it tasty and add those to kale to make it taste less bitter,” said An.
An grew up in the north part of China and never saw canola fields until he moved to the south part of China to attend college.
“As soon as I got to college, I remember thinking that [the canola fields] were so beautiful and that I wanted to study them,” said An.
For his Ph.D., An attended Huazhong Agricultural University and obtained his degree in crop genetic breeding. Although he has been working on his post-doc for three years, this isn’t his first time researching at MU. While he was getting his degree, he spent two years as a joint student in the Pires lab.
After his post-doc, An hopes to carry his knowledge of genetic crop breeding to a career at a seed breeding or biotechnology company.
“Many Brassicaceae are very important for us which is why it’s significant to find a way to make them more nutritious,” said An. “It’s important for people to know where our food comes from.”
International flights usually require months of planning to score the best deals and to ensure minimal layovers, so Sara Izquierdo Zandalinas, a post-doc in the Ron Mittler lab, was faced with a challenge as she flew to Spain twice within a month’s span this summer.
But the reason for those flights was a pleasant surprise. Zandalinas recently received the 2019 Sabater award given every two years at the Meeting of the Spanish Society of Plant Physiology held in Pamplona Spain from June 26-28. This award is a tribute to Francisco Sabater, a widely recognized plant physiologist of Spain, and is the most prestigious award given to early-career Spanish researchers in plant science.
“I couldn’t believe it because they told me I won one month before the conference,” said Zandalinas. “At that time, I was in Spain at another conference for 10 days, so I had to come back to Missouri and then I had one-and-a-half weeks to prepare a keynote presentation before I had to go back to Spain.”
Nonetheless, she was thrilled.
Zandalinas was recognized for her research on the role of Reactive Oxygen Species (ROS), a fancy term for reactive chemical species such as peroxides, in regulating plants responses to stresses and combined stresses, such as heat or drought.
“Studying combined stress is very important because with climate change, as temperatures are increasing, plants are facing not only one single stress in the field but also other additional stresses,” said Zandalinas. “Previous reports in this lab have shown that plants response to a single stress is completely different from the response of plants to multiple stresses.”
As a result, Zandalinas has spent the past two-and-a-half years identifying which genes are involved in acclimating plants to combined stresses. By selecting the genes that hold up well against certain stresses, scientists can begin to develop plants that are more tolerant.
When she was completing her undergraduate degree at the Polytechnic University of Valencia, Zandalinas recalls many of her friends and colleagues being drawn to the medical aspect of science. However, not many people were interested in studying plants.
Zandalinas, too, thought she was heading toward a career in the medical field until her final undergraduate project producing human antibodies in tobacco plants changed her mind.
“I remember thinking, ‘how is it possible that we can produce human antibodies in plants and in the future apply it to humans?’ I was fascinated by the powerful tools we have of using plants as bio-factories,” said Zandalinas.
From there, she received two master’s degrees in chromatographic techniques and analytical techniques used in clinical labs and a Ph.D. in plant biotechnology from Jaume I University in Castellon, Spain. Afterward, she began her post-doc with Ron Mittler at the University of North Texas before the lab moved to MU last fall.
While she enjoys having the resources for her research such as MU’s DNA Core and the Proteomics Center, Zandalinas dreams of the sunny skies and warmth back home in Spain.
Following the completion of her post-doc, Zandalinas hopes to establish her own lab back in Spain. She explains that it won’t be as easy to find a research position in Spain because so many people are completing their post-docs in the U.S. and Europe and are wanting to return to Spain.
“In one to three years I hope to receive a research grant from the Spanish government to begin my own research investigations,” Zandalinas said.
As a result of being awarded the 2019 Sabater Award, Zandalinas is now the Spanish candidate for the award for young European researchers in the biannual conferences of the Federation of European Societies of Plant Biology which will take place in Turin, Italy from June 29-July 2, 2020.
The discoveries from research capture the public’s and other scientist’s attention, but what about the tools, instruments and data management systems that provide more efficient means of getting there?
A new genome sequencing instrument is on its way to the Bond Life Sciences Center thanks to a Tier 1 grant from the UM system’s mission to enhance the ‘well-being for Missouri, the nation and the world through transformative teaching, research, innovation, engagement and inclusion’.
Wes Warren, primary investigator in the Bond LSC, led the effort to speed up the turnaround time for genome sequencing and lower the overall cost. The proposal for NovaSeq instrumentation additionally includes purchasing more data storage to keep up with researchers’ demand for the technology.
“This is an issue that has been noticed in the last three or four years around being able to generate the data in a high throughput fashion. A lot of our genomics researchers were required to seek these services off-campus,” said Nathan Bivens, Director of the DNA Core. “As part of this strategic initiative, we saw an opportunity for campus to invest in this instrument, make it available and then continue to build our own genomics resources here on this campus.”
With his experience with the McDonnell Genomic Institute at Washington University in Saint Louis for the past 17 years, Warren was the person to lead the charge in bringing this technology to MU.
“I was involved in some of the later stages of curating the human genome and I’ve been involved in many genome sequencing efforts at the McDonnell Genomic Institute, not only that but high-throughput sequencing in populations,” said Warren. “My work mostly revolved around comparative genomics. The experience factor that I brought to this proposal is knowledge of how to do high throughput sequencing and how to curate the data.”
Since the first human draft genome in the 90’s, there have been constant developments in sequencing technology to speed up the process and to do so at a lower cost. Sequencing figures out the order of A’s, C’s,G’s, and T’s that make up the DNA nucleotides, or bases, that define a genome that codes to build an organism.
Genomic and single-cell sequencing machines are ‘disruptive technologies’ which allow scientists to essentially have a blueprint of all of the genes that make up any given organism. These blueprints can be used for a variety of scientific purposes to study issues ranging from cancerous mutations to drought resistance in plants.
The data being generated from such technologies is allowing researchers to better understand scientific complexities such as cancers.
“We have an Illumina instrument that’s a different type of format in terms of its capability. It produces fewer bases per flow cell and as a result of that it’s more expensive,” said Warren. “It’s simply a question of cost here; the technology of the NovaSeq has improved in terms of the base accuracy but the main reason is that with more bases per flow cell, the more experiments you can do.”
The current technology in MU’s DNA Core costs about 30 percent more to complete similar sequencing and takes longer. The new technology can complete thousands of sequences at once, which means it will generate the data needed for publishing discoveries in a more timely fashion.
This cost-effective high throughput technology will allow researchers across the UM System to increase the number of samples they can test and to find genes of significance and traits of interest at a much faster rate.
“Since 2008, we’ve continued to see an increase in the amount of data that’s being generated on campus and the number of publications that are resulting from genomics research and data and I don’t think that’s going to slow down anytime soon,” said Bivens. “In five to 10 years I think we will still be generating more sequencing data especially with the new NextGen Precision Health Institute here at MU. We’re seeing more and more growth in areas which are going to use this type of technology.”
Inevitably, housing this technology at MU will create a higher demand for sequencing through the DNA Core Facility. To keep up with the demand for this data, Bivens said the facility is purchasing more data storage, restructuring the lab and potentially looking for an additional hire to help process the workload.
As for when the technology will be installed on campus and the DNACF personnel trained to use it, Bivens hopes to be ready to receive samples at the end of September, beginning of October.
This instrumentation is funded by the UM System’s and all four campuses strategic investment for research and creative works.
Cross-collaborative research team looks to refine delivery of cancer treatments
By Mariah Cox | Bond LSC
“When you want to use a tool to do something in the house, you have to use the right size tool. It does no good to use a large screwdriver to fix the tiny screw on your glasses.”
That’s Donald Burke, Bond Life Sciences Center lead primary investigator, as he begins to explain a project looking to optimize the targeting of cancer cells as part of a large cross-collaborative research team.
And the tools Burke is referring to are aptamers, single-chained synthetic DNA or RNA molecules. Aptamers are tricky molecules. Stemming from the Latin word “aptus,” meaning to fit, and “meros,” meaning part, aptamers must be complementary in size and shape to a certain cell-surface receptor in order to be useful as targeting tools, just like having the right size tool.
Last fall, Burke’s lab was able to identify aptamers as a specialized delivery method that have the potential to carry chemotherapy drugs and imaging agents, or cargo, as little backpacks to diseased sites. An important feature of aptamers is their three-dimensional structures which allow them to bind to target sites with high selectivity. That conceivably means they could deliver a drug to a particular part of the body, like a tumor, and not harm nearby tissues.
Now, the team, comprised of MU experts and researchers who specialize in surgery, radiology, molecular biology and immunology and chemical engineering, is hitting the ground running with a two-year research plan to refine the delivery of cancer treatments. The group was one of 19 innovative research projects across all four UM System campuses to receive a grant from a $20.5 million investment for research and creative works.
“Chemotherapeutics are not very specific and most of them act to block DNA replication or other functions of the cell in both healthy and cancerous cells,” said David Porciani a post-doc who started in the Burke lab in the spring of 2016 after finishing his Ph.D. in molecular biophysics in Italy. “Cells that are dividing are more susceptible to the chemotherapeutic effect, that’s why chemotherapy patients start losing hair.”
In general, therapeutic drugs don’t know to go only to tumors, and they don’t differentiate between cancer cells from healthy cells. The obstacle in only targeting cancer cells is to find specific indicative markers that are unique to tumors. Sometimes researchers have to make do with markers that are overexpressed on tumors cells, but those same markers can also be present in low levels on healthy cells.
The team is working simultaneously towards four major objectives – to identify a comprehensive panel of aptamers that target the majority of tumors, develop molecular tools to enhance the delivery of cargo specifically to cancerous cells, improve imaging for targeted delivery of radiopharmaceuticals, and enhance the efficacy of killing solid tumors through immunotherapy.
Each researcher bringing their unique expertise to the table play an important role in ensuring the project stay on track. Mark Daniels, an associate professor of Molecular Microbiology and Immunology and Surgery from the School of Medicine; Bret Ulery, an assistant professor in the Department of Biomedical, Biological & Chemical Engineering; and Donald Burke, a professor of Molecular Biology and Immunology in the School of Medicine and joint professor of Biochemistry, have been instrumental in the project since its beginning stages.
A collaboration years in the making
“Daniels, Ulery and Burke labs have been collaborating for a number of years, each of us excited about what the other could bring to the collaboration,” said Burke. “[Over the years] we’ve explored several ways of making things move forward, we’ve figured out some productive ways to work together and we’ve identified the key questions that we could pool our respective expertise toward answering,” said Burke.
Daniels’ subgroup of the project has been using flow cytometry, a technique used to detect and measure biochemical and molecular characteristics of tumor cells to see which ones are recognized by a set of different aptamers.
Additionally, Ulery has provided extensive insight into the different ways to package molecules together so that they can move around the body and get to where they need to go.
The grant comes as part of the combined UM system’s and all four campuses mission to supply funding for opportunities that will enhance the ‘well-being for Missouri, the nation and the world through transformative teaching, research, innovation, engagement and inclusion.’
For Burke, the grant couldn’t have come at a better time.
“This team has existed before the announcements were made that there would be these opportunities and so when they announced we said that this was tailor-made for us,” said Burke. “It was just the right time for us. Had they had the same competition three years ago, we weren’t ready for it. Had they had it three years from now hopefully we wouldn’t have needed it anymore and we would’ve already gotten the project to the next level.”
Another key player in the development of this discovery is David Porciani. He has spent three years trying to create ‘smart’ molecules that know exactly where to bind without damaging healthy cells, and he has been working on the project since its beginning.
“There are several ways to target cancer cells. Even on campus, there are different groups that are trying to target cancer cells differently and, in my experience, every strategy has advantages and limitations,” said Porciani. “What I see for this aptamer strategy is that it can provide new molecules that can bind to receptors, and it can also identify new tumor biomarkers.”
Porciani’s portion of the project includes using the advanced microscopy capabilities of the MU Molecular Cytology Core to visualize the kinds of receptors on the surface of cancer cells. This information can be very telling in identifying receptors that are specific only to cancerous cells.
What the future holds
The project now starts down this ambitious road. In the first year, the collaborators are working on discovering their panels of aptamers, developing lung cancer-specific T cells which provide artificial cell receptors for the use of immunotherapy, and beginning testing of the specificity of aptamer-cargo constructs in samples acquired from the American Tissue Cancer Collection. By year two the group hopes to begin testing in biopsy tissues acquired from MU hospital patients acquired under informed consent and in lab mice.
“After we test a specific drug in cell culture samples and see an anti-cancer effect, killing only the cancer cells and leaving the healthy cells, we expect to see the same effect in biopsy tissue samples,” said Porciani. “Having a reduction of the tumor mass and not having side-effects is what we hope to see in biopsy tissues and mice.”
After the end of year two, the team is looking forward to expanding this research to other types of tumors to see if their tumor-targeting method can apply in different cancer types.
“Our team has been trying to piece this together for a long time and it’s been surviving on goodwill up to this point. This is the most substantial funding we’ve had for it to date and we’re really excited that the University of Missouri has chosen to support us on this,” said Burke. “We’re very hopeful that we can use it as the starting point for building a much larger enterprise centered around tumor targeting in general, whether it’s for therapeutics, diagnostics or other purposes.”
Donald Burke is a primary investigator in the Bond Life Science Center and is a professor of Molecular Microbiology & Immunology in the School of Medicine and a joint professor of Biochemistry and Bioengineering. David Porciani is a post-doctoral researcher in the Burke lab. Mark Daniels is an associate professor of Molecular Microbiology and Immunology and Surgery in the School of Medicine. Bret Ulery is an assistant professor in the Department of Biomedical, Biological and Chemical Engineering in the College of Engineering. Other key collaborators on the project include Diego Avella Patino and Jusuf Kaifi in the Department of Surgery and Jeff Smith in the Department of Radiology.