Scott Peck studies Arabidopsis and how bacteria perceive it before initiating an infection. Roger Meissen | Bond LSC
By Madelyne Maag | Bond LSC
Bacteria and disease show no mercy to any organism they can effectively attack, including plants.
Yet, plants can also develop an immune response against these threats from their complex genetic makeup.
Scott Peck’s research delves into how plants do this and how bacteria evade those defenses.
Over the course of the last decade, the Bond Life Sciences Center investigator and professor of biochemistry has specifically looked into how plants are able to initially perceive and respond to potential bacterial threats through phosphorylated proteins and pathogen-associated molecular patterns.
“The overarching goal really with all of this research is to improve a plant’s resistance to potential pathogens in order to decrease crop loss,” Peck said. “That’s hundreds of millions of dollars lost every year to disease, so then that’s less food available and higher costs in the market.”
Peck recently published new work from his lab that observes how plants receive messages from potential pathogens and how they develop an immune response to these pathogens on a genetic level.
Similar to humans and animals, plants have a sensory immune response to know when a foreign object, such as a potentially infectious pathogen, shows up. One way they do that is by using receptors to detect certain molecules particular to an enemy like bacteria or viruses when they encounter the surface of a plant’s cells.
These pathogen-associated molecular patterns, or PAMPs, are recognized by the plant’s innate immune system and cause the plant to create a chemical defense against them. More specifically, when PAMPS are perceived, cells activate messenger proteins called mitogen-activated protein kinases (MAPKs), which signal the plant of a potential problem. Because too much defense signaling can be harmful, another protein, MAP kinase phosphatases (MKPs), helps the cell determine how much of a defense response the cell should make against the enemy.
To better understand the plant’s processes of recognition and response to a potential pathogen, two separate studies analyzed how MKP1 is regulated and which cellular pathways are regulated by MKP1.
“For one of the first times, these studies using MKP1 gives us a large, specific set of gene markers to define individual pathways that respond after perception of bacteria,” said Peck. “We can now specifically take individual genes and know how they work and where to place them like a Jigsaw puzzle.”
Both of these studies are able to help us better understand how one particular plant protein reacts to a potential threat.
Peck made it clear that proteins and responses are altered during defense responses.
The next step would be to better understand how these processes interact to help the plant defend itself against a variety of pathogens.
“By really understanding how the plant does what it does under the best circumstances, we can try to then, either through traditional breeding or engineering, get plants to grow and reproduce without being as vulnerable to pathogens,” Peck said.
Tom Quinn, director of the Molecular Interactions Core, and others demonstrate equipment for its Jan. 24 open house. | Photo by Katelyn Brown, Bond LSC
By Katelyn Brown | Bond LSC
For researchers, the shape of molecules gives insight into how cells, viruses and other macromolecular interactions take place.
Getting a clear view of that structure is the hard part, and the new Molecular Interactions Core (MIC) at the Bond Life Sciences Center will now give researchers from many different disciplines one place where state-of-the-art equipment are available for them to use to further science.
Dr. Kamal Singh is excited that goal is being realized.
One of the 10 MU’s core facilities that serve scientists’ needs, the MIC specifically provides training, advising and shared equipment for researchers to take a closer look at molecules.
That’s where Dr. Singh comes in.
He serves as the Assistant Director of the MIC and oversees the day-to-day operations of the facility. Dr. Singh makes sure the machines are operational, communicates with researchers interested in using the facility, trains those who do not yet know how to use the equipment and gives guidance as well as collaborative feedback on things like computer-assisted drug design — his specialty.
The humming of machines is the first thing noticed when walking into the MIC. These instruments allow you to look at 3-dimensional models of the molecules like HIV enzymes or view protein crystals under a microscope before diffracting light through them. It’s a lab where miniscule pieces of life become big and important.
Dr. Mark McIntosh, the vice chancellor of research for all UM system campuses, had the idea to create the MIC.
“It was Dr. McIntosh’s vision to bring everything together; which includes structural biology, molecular interactions, particle size, zeta potential, mass of the nanoparticles, etc. He also wanted to bring peptide synthesis here to have everything at one central location,” Dr. Singh said.
Understanding structure at the molecular level helps scientists figure out how reactions happen, how molecules fit together and serve as signals and how pathogens can invade cells, among other possibilities.
“I’m hoping that we can really facilitate structural and molecular research on campus — structural determination and molecular interactions — and really push boundaries of the current state of the field,” said Dr. Tom Quinn, the Director of the MIC.
Dr. Quinn hopes the state-of-the-art equipment will allow the MIC to be a resource for both research faculty and students to be on the cutting edge in their fields.
Dr. Ritcha Mehra-Chaudhary and Dr. Fabio Gallazzi work within the MIC and provide their expertise. Dr. Mehra-Chaudhary works with X-ray crystallography, dynamic light scattering and custom protein expression, while Dr. Gallazzi is an expert in custom peptide synthesis. Their work can be important for understanding drug design to combat viruses and cancers.
The MIC started with one machine, an X-Ray Diffractometer, in room 442 of the BLSC. It took six months to collect the different machines from different departments in the campus, but in December the MIC became fully operational. The MIC team celebrated with an open house on Jan. 24, 2018.
“It’s kind of crowded, but it’s good,” Dr. Singh said. “We have invited everyone, mainly researchers, but also undergrads. The entire university is welcome to come see what we have. The idea is the advancement of science in our school.”
The MIC won’t only be beneficial for campus researchers, but also researchers from all over and undergrad students who are eager to learn the details of molecular interactions and learn how to use core facilities.
There are many exciting and new technologies in the MIC that will interest outside researchers, according to Dr. Quinn. One of these is the nanodisc technology that Dr. Mehra-Chaudhary works with. This technology allows researchers to study membrane proteins outside of something bigger, like a cell, while also keeping them in a functional and native structural state. The nanodisc project is part of collaboration between the MIC and the Electron Microscopy Core to allow researchers to get high resolution structures of membrane proteins.
While affordable, outside and campus researchers must also pay a price to use the facilities to cover consumables, instrumentation maintenance and staff.
“We definitely want to at least break even. I don’t know how long it will take to get there. However, the major goal is to support the scientists on campus and facilitate their research,” Dr. Singh said.
Bringing this support to campus also means supporting future scientists. Dr. Singh has three undergraduate students working with him who are learning how to use the advanced technology, and he helps to train many more from all different departments.
The goal is to one day expand the MIC to a point where all molecular interactions facilities can be at one place.
“There are certain techniques we don’t have, and I hope that in the future we will get them. We hope to provide all modern techniques to the university community in coming years. Not only linked to that room, we want to expand it,” Dr. Singh said.
Dr. Quinn agrees, and he hopes that as researchers come and use the core. In the process the core can understand future needs and where the research is moving to see what new technology under their umbrella could be added to keep supporting the scientists.
The MIC is a big step for the MU research community, and staff is hopeful that it will continue to grow and produce life-altering research.
Soybeans are used to screen for genes connected to traits that resist soybean cyst nematode. Recent progress by the the Mitchum lab explores how the plants combat the parasite and how the parasite sidestep genetic protections.
By Samantha Kummerer | Bond LSC
It might not sound like a traditional undergraduate experience, but Elizabeth Prenger and Andrew Ludwig found success studying a tiny parasitic worm.
It’s called the soybean cyst nematode (SCN) and it sucks more than a billion dollars a year from American soybean farmers. While farmers have used resistant soybeans and crop rotation to fight against the pest, the nematodes continue to gain ground against increasingly less effective methods to control them.
Working in the lab of Melissa Mitchum, a Professor of Plant Sciences at MU’s Bond Life Science Center, they helped understand how soybeans naturally resist this worm and how SCN evades these protections.
That work recently paid off as they saw their names published in the journal Plant Physiology in November 2017. The study explored the genetic mechanisms behind resistance in order to develop better prevention.
Elizabeth Prenger studied soybean resistance to soybean cyst nematode in the Bond LSC lab of Melissa Mitchum, leading to a recent publication in the journal Plant Physiology.
“If scientists can understand how resistance genes work and interact then that information can be applied in breeding and developing soybeans,” said former Mitchum lab member Elizabeth Prenger.
While the findings were published in 2017, for Prenger and Andrew Ludwig the research began several years ago.
Prenger came to college knowing she wanted to improve crops and help farmers like her family, she just wasn’t sure exactly how. She joined Mitchum’s lab as a freshman to begin to find out.
As a freshman and sophomore, Prenger worked to purify, sequence and analyze DNA of various soybeans to help further characterize the SHMT gene, a gene that plays a role in a plant’s ability to resist the pest. She also worked in the greenhouse to identify soybeans with mutations in this gene by infecting them with SCN.
Her fellowship supported by the MU Monsanto Undergraduate Research Program sparked her interest in plant genetics but she also realized she wanted more interaction with plants beyond the lab.
Without this early immersion into the lab, Prenger said it would have taken her longer to find her interests.
Now, as a graduate student, she studies soybean genetics at the University of Georgia.
Andrew Ludwig presents some of his research on nematode resistance at Missouri Life Sciences Week 2017 | Photo by Jinghong Chen, Bond LSC
Ludwig’s position in the lab helped him find his direction in science as well.
He applied for a position while still in high school through the MU Honors College Discovery Fellows Program. The fellowship funds and places undergraduates in labs across campus. His interest in the genetic modification of crops led him to the Mitchum lab.
For three years, Ludwig helped infect different mutants with the nematode and then compare the effect on resistance. This screening helped narrow down the genetic possibilities controlling soybean resistance to a single gene.
“We were hoping the soybeans would have a mutation in one of the resistance genes and then that mutation would cause the gene to cease function so you would see a lot of nematodes on a plant that shouldn’t have any,” he explained.
This experience taught Ludwig how to think like a scientist by developing problem-solving skills.
“I think working in the lab was an immensely valuable experience because I learned so much about what it is to be a scientist and it opened my eyes to a lot more of what the field of plant science really is,” he said.
It also taught him that a traditional lab work environment was not for him. As Ludwig begins to apply for graduate school he is planning to major in horticulture.
His goals changed from wanting to create GMO crops for other countries to now hoping to solve food insecurity closer to home by working with sustainable agriculture and food deserts.
Since joining Mitchum’s lab as undergraduates, both Prenger and Ludwig learned what it means to be scientists and shaped where they are today. The publication of the research that started the path to where they are today was a satisfying conclusion.
“It’s really rewarding to see that all the work exists outside of my lab notebook now,” Ludwig said.
Reflecting on their experience, both students urged other undergraduates to get in a lab as soon as they can to begin discovering themselves and science.
“Go for it. It’s a really helpful experience, it will make you better at what you do even if what you end up doing is different from what you thought you’d do,” Ludwig recommended.
Bond LSC connects scientists in “hot topic” research
Alexander Franz presents his research on arboviruses and mosquitoes to the Host/Pathogens Research Network. The network brings researchers from across campus together to foster cross-discipline research. | Photo by Samantha Kummerer, Bond LSC
By Samantha Kummerer | Bond LSC
An immunologist, a plant biologist and a biochemist enter a room.
No, that’s not the start of a geeky science joke, but rather is the start of a conversation meant to spur ideas.
As a group of scientists crowd a conference room in the Bond Life Sciences Center in December, they aim to share ideas about their diverse research projects and disciplines.
Today they set about to learn about viruses in mosquitoes from Alexander Franz of MU’s Department of Veterinary Pathobiology.
“The take-home message is that mosquitoes are not just flying syringes or something,” said Franz, explaining the basic science behind his studies. “That is the very wrong idea. This is a very intricate relationship between the virus and the mosquito.”
He spoke to the scientists in attendance about the Chikungunya virus that is spread by mosquitoes to humans throughout the world and currently has no vaccine. Franz’ work examines the genome of the virus and the virus’ expansion into secondary tissues.
The scientists are part of a research network focused on Host-Pathogen relationships. This overarching topic unifies researchers from across campus who share this commonality. The hope is to spark shared projects between scientists that often find it difficult to make connections outside of their discipline.
This group is one of three hot topic areas Bond LSC is currently targeting to get the conversation started. Researchers across campus joined this network two months ago along with groups interested in metabolomics and cancer biology.
During each meeting, one researcher volunteers to present their work to the group and other members are able to jump in, ask questions or offer advice to bounce ideas off one another.
Bond LSC interim director Walter Gassmann kick started the meetings, recognizing both the need for collaborative research and the central location of the Bond LSC building.
“The increasing complexity and sophistication of basic research leads to increased specialization. Yet, fundamental questions can only be tackled by getting at them from different directions,” Gassmann said.
The LSC has always encouraged collaborative discussions for scientists within the center, but Gassmann decided to expand these to include faculty from all buildings on campus as well as include students in the conversation.
“When I became the interim director, I felt Bond LSC could really function as a catalyst for a wider research community on campus. This meant advertising the “hot topics” meetings across campus,” Gassmann said.
Bond LSC investigator Michael Petris said previously multiple small cancer research groups met, but these meetings expand the group and centralize everyone.
Petris is one of the leaders of the cancer biology group and said the effect of these talks is already showing.
After Petris gave the first talk for the cancer biology group, he was invited to exchange techniques, ideas and cell lines with another researcher who was in attendance.
“The discussions that go on in these sort of groups are, for me at least, opening my eyes to the broader spectrum of cancer biology that goes beyond my wheelhouse, my sort of understanding from a narrow perspective,” Petris said.
One way this is occurring is due to the inclusion of clinicians who deal with patients regularly. Petris explained their perspective on problems in cancer and biology may be something the cancer biologist never even thought of before.
The center supports these talks with the aim of sparking collaborative research, publications, and grants in the future.
A full schedule of spring 2018 hot topic meetings will be released in January.
Proteomics Center associate director Brian Mooney holds up a sample before using a machine to collect data on its proteins. | Photo by Samantha Kummerer, Bond LSC
By Samantha Kummerer | Bond LSC
The Proteomics Center runs on proteins.
This research core facility is like a small business and is situated in the Bond Life Sciences Center. It has helped improve agriculture, opened doors for new medical applications and lead to greater insight into human diseases.
Proteins are some of the most plentiful and common building blocks of all living organisms, making structures in cells but also are key to antibody defense, enzymes to carry out chemical reactions and as messengers to coordinate biological processes.
This complexity makes an essential building block far from simple.
Figuring out what proteins exist and how they function is key to many experiments and that’s where Mizzou’s Charles W. Gehrke Proteomics Center comes in.
The Center looks at thousands of proteins with their current technology consisting of six mass spectrometers worth more than $2 million. They serve clients across the UM System and as far away as Mexico and Canada.
At its core is Brian Mooney, associate director of the center and Roy Lowery, an expert in protein isolation and fractionation and is also learning mass spectrometry.
The Center is often juggling multiple clients each week and sometimes each day. For each new project Mooney sits down with researchers, helps them develop an experimental design, and takes their samples to generate data.
“Sometimes you get to that Eureka moment and you say, ‘I thought this was happening but my hypothesis was wrong and actually this is happening’ and leads to new directions in research. That’s what we’re here to do,” Mooney said.
The center is able to run experiments that look at proteins from a global scale and experiments that target just a small number.
For studies that want to find the difference between a normal cell and a mutant, a global analysis is used to look at all the proteins.
Mooney breaks a cell down and removes everything but its proteins. This fractionation allows researchers to examine a lot more proteins more closely.
“Typically the things that are doing the control in the cell are maybe not as abundant, so you need to dig deeper, so that’s the point of the fractionation,” Mooney explained.
To look even deeper into these, the center can use a technique called SDS-Page to sort the proteins by size.
“We’ve done everything from full plants so leaves and roots, we’ve done it for bacteria cells, we’ve done it for blood, both in humans and in animal models and then we have also done some specific tissues whether it be heart or kidney,” Mooney said explaining the range of this technique.
Brian Mooney looks on to data collected on proteins in the MU Proteomics Center.| By Samantha Kummerer, Bond LSC
“We were able to see specific proteins that were involved in processes that suggest this is why you get a taller and healthier hybrid plant,” Mooney said. “One of the major findings was elevated stress-responsive proteins conferring an ability to withstand stress.”
The center also helped researchers at the Truman Memorial Veterans’ Hospital compare heart tissue between healthy and diseased hearts.
With a targeted approach, the clients already know what proteins they are interested in, so Mooney is able to use equipment to zero in on a much smaller number.
“We are working in a group in biological sciences that are looking at nerve tissue and in this case they are just interested in five proteins and what we’re able to do is ignore everything else and get really good numbers in how much of these five proteins are there,” Mooney explained.
The center is also there to educate. Mooney explained often clients don’t have a clear understanding of proteomics.
This mission of education also occurs for students. Graduate students and post-doctoral students are trained on how to work the instruments and to analyze the results. On the undergraduate level, Mooney presents hands-on lectures and labs to biochemistry classes. The Center also participates in a unique MU-Industry undergraduate internship program (Biochemistry Dept. and EAG, Columbia).
Sometimes the exposure of what the center’s capabilities sparks cross-discipline projects.
In 2015, Mooney worked on a collaborative project with the MU Medical School studying cataract formation in humans.
Last year, Mooney teamed up with biochemists and mechanical and aerospace engineers.
Mooney explained that before the involvement of the Proteomics Center, the researchers were firing a laser at a piece of a protein called a peptide.
“They saw that something weird happened and wanted to know what that weirdness was on the molecular level, so they came here,” Mooney said.
This collaboration led to a publication on how targeting proteins and peptides with a laser can control biological processes in cells and tissues.
MU is not the only university with a Proteomics Center, but having it local comes with a number of advantages. Mooney said subsidies from MU allow the center to offer reduced rates to MU clients. Another advantage is the ability to consistently have someone nearby to talk through their experiment with.
Since 2002, the center has grown from a handful of customers to more than 50 customers a year and a total budget of about $250,000. Direct income from research usually covers about 60-70% of that total, with the remainder being covered by the Office of Research.
Mooney said part of this success and growth is due to an increase interest in proteomics from scientists.
While genes allow researchers to know what might be in the cell and mRNA tells them what is going to be in the cell, the proteins reveal what is currently in the cell.
Many researchers have focused on cells at the DNA and mRNA level, but are now discovering it’s important to consider the protein as well.
Soon a new instrument will be added with funds received through a National Science Foundation MRI grant, one of two awarded to MU in the last 10 years. With the upgraded mass spectrometer, Mooney said, data will be able to be collected faster and better. This advancement will continue to allow the center to do what it does best – proteins.
The MU Proteomics Center is named for Charles W. Gehrke, a former MU professor of Biochemistry. It is one of 10 research core facilities subsidized by MU’s Office of Research to provide services to a range of scientists and researchers across the UM System and the world.
A soybean plant grows in the Bond Life Sciences Center’s greenhouse. | Photo by Samantha Kummerer, Bond LSC.
By Samantha Kummerer | Bond Life Sciences Center
Every summer, MU Bond Life scientists Gary and Bing Stacey plant soybeans. In the summer of 2016, they were testing mutant crops’ tolerance to different herbicides. Among the multiple weed killers tested was one called dicamba.
The researchers knew this particular chemical was tricky so they turned to an expert to apply it, MU herbicide researcher Kevin Bradley.
The next morning, a soybean breeder with a neighboring plot discovered his soybeans were damaged.
“These were plots where some of his graduate students experimented so they basically couldn’t use any of their data and we felt terrible, but we explained to them we took every precaution we could possibly take but it was this vaporization that took place,” Gary Stacey explained.
What Gary Stacey didn’t understand at the time was dicamba has an ability to travel even after it is sprayed. The herbicide doesn’t just kill weeds, it kills or damages everything not engineered to be resistant to it.
“So let’s say I spray it in this spot right here. You would think its localized but if the temperature and humidity conditions are right it will vaporize and come up and then go into the air,” Gary Stacey said.
Just how far it can travel and how much damage it can achieve was realized all too well by farmers throughout the country this year.
An estimated 3.5 million acres of soybeans were damaged this summer.
One obvious solution may be to simply stop using the weed killer. But the issue is not that simple.
“This is the hardest issue I can remember because there are good responsible farmers on either side of the issue,” said Missouri Farm Bureau president Blake Hurst.
With so much on the line for all sides, dicamba has tangled farmers, corporations and researchers together in a controversial issue.
Bradley is right in the middle. He’s received calls from farmers who just lost 10 percent of their income for nothing they did wrong.
He’s also received calls from people who are upset by any suggestion that anything about the chemical is wrong. These are the farmers who need dicamba to control weeds that are no longer responding to the traditional weed killer Roundup.
“I’ve had the farmers who planted the traits saying ‘These are my highest yields ever how can you say these things?’ And their neighbor across the road just lost 20 bushels an acre because of your highest yields ever. It’s just a very personal issue for each person involved,” Bradley explained.
One case got so personal that a farmer in Arkansas allegedly shot his neighbor.
“I’ve been here for 14 years and I’ve been doing this kind of work for 20, never seen anything like this is agriculture. Period. Never seen this level of controversy between farmer to farmer and farmer to company or between company and university people. I’ve never seen anything like this,” Bradley said.
Dicamba is not a new formulation, but its use is. Monsanto developed genetically modified soybeans and cotton seeds that are resistant to dicamba. One of the problems farmers are pointing to is that Monsanto released the new seeds while still in the process of developing a better formula of dicamba. The new formula aimed to reduce volatilization, a tendency to vaporize after being sprayed on fields and then drift to neighboring areas. Monsanto claims the new formula reduces volatility by 90 percent, but Bradley said 90 percent is not 100 percent.
Bradley’s work has been consumed by this single herbicide as he tries to find the truth of what aspect of dicamba is causing the damage.
In Bradley’s eyes, there are four factors contributing to the widespread damage: physical drift mistakes (spraying with the wind, nozzle not attached correctly), tank contamination, temperature inversion, and volatility.
These factors are recognized by other researchers and Monsanto. The disagreement is over which factor is most at fault.
“Monsanto has a pretty high number for the farmer fault percentage,” Bradley said explaining the blame game. “ I don’t know when they’ll ever really say, ‘yeah, volatility could be contributing to this problem, too’ and that’s the difference between university weed science.”
This contributes to the confusion among users.
“You don’t know who to believe,” Gary Stacey said.
But Gary Stacey thinks this is where researchers are able to help. By acting as an objective third party, scientists can sort the fact from the fiction.
“We’re just trying to get out the truth and what science says, that’s my job,” Bradley explained. “I don’t care necessarily what amount of money a company has invested in something. Our job is to call it like we see it and show the science.”
With a controversial issue like this, sometimes the truth comes with some risk.
MU has been conducting experiments that test the air for the volatility of the chemical. The research is detecting dicamba in the air up to four days after initial application of the chemical. Bradley explained this is not something the companies want to be made public and there’s been considerable pushback.
In addition to research, Bradley is working with the Missouri Department of Agriculture to create training courses for farmers wanting to use the chemical next season.
Despite millions of damaged acres, dicamba is not going away anytime soon.
Gary and Bing Stacey haven’t used dicamba again, but many farmers making their money off crops have no choice. Bradley said Monsanto is planning on doubling the amount of dicamba-resistant soybeans in 2018 and many of the farmers who have been continuously hit by their neighbors’ chemical plan to plant the new seeds.
Bradley said part of the issue is soybeans are not a crop people directly consume. In general, soybeans yields were considerably high this year, so the damaged acres didn’t make as big of an impact on overall production.
“I think the only thing that is going to make a difference next year is if we have an off-target movement that is hitting more high-value crops, more high-value plant species throughout a wider geography,” Bradley said.
If this same type of damage was affecting produce people directly consume or trees, Bradley thinks dicamba would have been off the market by now.
EPA will reevaluate the use of the herbicide next November. This is one of the first times Bradley can remember that the industry granted only a two-year registration.
“I am absolutely convinced that if we have a summer in 2018 like we had in 2017, it will not be renewed,” Hurst said.
Bradley is not so certain. He said he has heard mixed reviews about how the future of this controversial weed killer could go.
“It is an unique situation for sure, hopefully it ends soon,” Bradley said.
Roberts honored for breakthrough discovery in reproductive biology 30 years ago
By Eleanor C. Hasenbeck | Bond Life Sciences Center
In 1987, Michael Roberts published a groundbreaking discovery that changed the world of reproductive biology research.
Roberts and members of his lab discovered that a type of protein, an interferon, impacted how the bodies of animals such as sheep, goats and cows, recognized an embryo early in pregnancy. Previously thought to only be a part of a cell’s immune system response, this new signaling role changed the field.
In honor of his lab’s groundbreaking discovery, Roberts recently curated a section of six reviews examining the history of the discovery and current research that has built on it for the November issue of the journal Reproduction.
The discovery revealed an unknown in the reproductive systems of the ruminant family of animals, including sheep, goats, cows and deer. When an embryo first begins developing, before it’s placenta even attaches to the uterus, it releases interferons. Only present for a few days, these proteins signal to the mother’s body that the embryo is there. It triggers the response that keeps the animal from going into heat, basically shifting the animal’s hormones from breeding mode to pregnancy mode.
If the embryo doesn’t release interferons, the mother miscarries. Placing interferons in sheep that were not pregnant made the animals pseudopregnant, a false pregnancy in which no fetus is present.
Scientists at the time knew something made the mother’s body recognize the embryo, but they were not sure what. The discovery of interferon-tau was a mystery solved. That this ‘something’ was an interferon was also a surprise. Before Roberts and his co-discoverer, Fuller Bazer, found interferon-tau, researchers thought that interferons only function was in the immune system. Other interferons help the body recover from viral infections, like cold and influenza, Roberts said. The discovery that the protein also played a role in pregnancy caused some hubbub. It even caught the attention of The New York Times, Roberts said.
“It opened up a whole new area,” he said. “We all the sudden understood how these animals got pregnant, so people went off in all sorts of directions with it.”
The discovery of interferon-tau created opportunities for more research in how ruminant’s unique reproductive systems evolved. Other studies focused on using interferon-tau to improve livestock fertility, but ultimately this interest fizzled out as researchers found fertility treatments for cows were cost-ineffective for producers and unappealing to the public.
The discovery of interferon-tau earned Roberts and his co-discoverer the Wolf Prize in agriculture in 2002. Some consider the prize an equivalent to the Nobel Prize since the Nobel prize does not regularly honor agriculturalists.
After the discovery of interferon tau, Roberts found another protein that impacts pregnancy, which formed the basis of a pregnancy test for cows. Roberts said it’s now a multi-million dollar product in the cattle industry.
Today, Roberts’ lab has moved to other developmental research. He started studying human placentas. His work focuses on preeclampsia, a condition which impacts 5-10 percent of all pregnancies and is caused by the placenta. Roberts’s lab has also developed new lines of pluripotent pig stem cells which are helping scientists learn how to regenerate eye and heart tissue. At age 77, he is still funded and active.
Saturday Morning Science talks engineering our next defense
Chemical engineering students Caitlin Leeper and Rui Zhang work in Bret Ulery lab. The lab conducts innovative research combining chemical engineering with immunology.| Photo by Samantha Kummerer, Bond LSC.
By Samantha Kummerer | Bond LSC
Saturday Morning Science brings science to the people, bagels included. In an effort to highlight this outreach effort, we’re profiling a recent SMS speaker who talked about … well, read for yourself below.
Inside your body is a complex network of interlocking biological pieces. Tissues, cells and organs are consistently working together to defend against an outside attack. This is the immune system, the body’s natural defense mechanism, which is incredibly important to keeping us healthy but are we currently using it to its full advantage?
Chemical engineering Professor Bret Ulery feels we have gotten a good start, but overall the answer is still a resounding no.
“We have this unique opportunity to leverage the things that are going on to make a difference in the immune system,” said Ulery, the Assistant Professor of Chemical Engineering and Courtesy Assistant Professor of Bioengineering.
Ulery runs a lab within Lafferre Hall centered on creating designer biomaterials.
He describes biomaterials as any substance that carries out a biological function which are commonly created to avoid interfering with the immune system. They can be used to replace a knee joint, a heart valve, or even contact lenses to correct vision.
“That’s been very successful for a long time in certain areas but what if we want to tackle some grand challenges?” Ulery said. “We may want to rethink what we’re doing with biomaterials and how we design them.”
To take on these bigger problems, his lab leverages the chemical and physical properties of materials to facilitate unique biological functions in regenerative medicine and immunology.
Vaccines seemed a logical place to start. A vaccine introduces a portion of a pathogen to a patient so they can be exposed to just enough to create an immune response without developing the actual disease. Ulery explained a person does not get sick from a vaccine because it is designed to target both the innate and adaptive immune responses without having the capacity to induce illness.
Traditionally, there are just a few ways to create a vaccine. First, scientists use heat or radiation to inactivate a pathogen. It is killed so the patient will not be exposed to the full disease but the immune response will still be triggered. While this type of vaccine is safe and easy to transport, the immune response it induces is weak and thus requires a great number and more frequent immunizations to be effective.
Another method is to keep the pathogen alive but to knock out its disease activity like what is done with the flu shot. Scientists take out part of the virus but keep it alive. This way the virus can still grow but won’t create the same degree of damage as the normal pathogen. Here, the immune response is stronger but not always equally effective in everyone due to differences in viral strains that have mutated to get around certain immune defenses.
Ulery wants to engineer more effective vaccines by only exposing the patient to the components absolutely necessary.
“We wouldn’t have to worry about any of this other bacterial gunk that would be with it. However, the problem there is the immune response is very weak because all that other junk actually plays a role in inducing the immune response, but it’s a lot safer, we can make it cheaper, make it easier to transport,” Ulery said. “We can do a lot of manipulation.”
This manipulation involves taking a portion of a protein called a peptide and tethering a fat to it. This new molecule called a peptide amphiphile folds in water in unique ways to create interesting nanostructures called micelles.
“Instead of having some sacrificial material where we load our drug or vaccine into the core, this is actually a nanoparticle that is made almost entirely from the vaccine itself, so we get really high concentrations of the peptide and the vaccine,” he said, explaining the benefits.
By adding different peptides, the lab is able to create a vaccine that works for multiple types of infections. Ulery said his team is working towards applying these techniques to combat diseases such as Lyme disease, influenza and even cancer.
Current methods of targeting cancer are tricky because of the similarity between cancer cells and healthy cells. Ulery said it’s difficult to make a vaccine that just kills the unwanted cells.
Despite the challenge, Ulery and other researchers at MU think they found a molecule that is good at killing cancer cells without hurting healthy cells. Initial tests revealed engineered micelles can be used to deliver a peptide drug to allow patients to receive smaller doses because the treatment kills more cancer cells in a targeted area. Ulery explained the exciting part of this is the method does not require changing the immune response.
But what if the team did use the immune system to improve treatments?
The chemical engineer explained there are immune cells within a cancerous tumor. However, the tumor’s environment prevents the immune system from doing its job. Ulery believes it might be possible to retrain the immune system to kill cancer.
That method would be similar to how vaccines are created. Instead of modifying portions of a protein, scientists could modify tumor cells so the immune system could process them easier. That’s one possibility but an even better option would be making a vaccine specific to a patient. Ulery said this would be the third generation of immunotherapy where different therapies work for different areas.
Much of Ulery’s work at MU is just starting to touch the surface of its potential, but the lab continues to challenge traditional immunology notions as it aims to create better solutions.
Ulery’s spoke Sept. 30 as part of Saturday Morning Science. The series invites speakers in all types of science to speak every Saturday at 10:30 a.m. This outreach effort is free and open to the public. Find its schedule speakers at bondlsc.missouri.edu/saturday-morning-science/schedule.
A new test can show how much a zebrafish larva has eaten. This basic information could be crucial to upcoming discoveries.
A zebrafish swims in its tank. Understanding how zebrafish move can give researchers insight into how certain diseases impact human motion. Photo courtesy National Institute of Child Health and Human Development.
By Eleanor C. Hasenbeck | Bond Life Sciences
Until now, it was hard to know when a zebrafish larva had a full stomach.
Researchers in Anand Chandrasekhar’s Lab at the Bond Life Sciences Center are studying the networks of neurons that control the zebrafish’s jaw, but to do that, they first had to figure out just how much these fish larvae eat.
They didn’t just need to understand it, they had to be able to test it. The successful development of a test that measures how well a zebrafish larva can eat has already lead to more discoveries.
To develop this test, researchers fed the larvae fluorescent fish food for three hours at a time. That’s just long enough for them to eat it, and just before their intestine starts to push it out. Their tiny, fluorescent bellies were examined under a microscope and scored. A zero meant that there was no food in the larva’s stomach, while a three meant the stomach was completely full.
With this feeding test under their belts, researchers are now able to form and test more research questions. The Chandrasekhar Lab used it to better understand networks of branchiomotor neurons, the circuitry that controls jaw movement. These neurons also control the gill muscles that move in automatic movements, such as breathing, just as neurons in the human brainstem allow us to breathe without thinking. Researchers look at the zebrafish’s very basic motor neurons to understand how these nerves develop, heal and control simple tasks.
One experiment tested how fewer branchiomotor neurons affect the action of eating. They destroyed 50-80 percent of the larvae’s branchiomotor neurons using a chemical-genetic method. The fish with fewer branchiomotor neurons also ate less food. They tried a similar experiment, but this time using lasers to remove only a select portion of branchiomotor neurons that controls a set of jaw muscles. Again, they found that the larvae that went under the laser were not able to eat as much food as the normal larvae. Finally, they conducted the food-intake test with mutant larvae that did not have any cranial motor neurons. As the researchers predicted, the mutants were not able to eat.
Now, they want to test how these animals eat when these neurons develop differently. While the first tests essentially smashed nearly all of the zebrafish’s branchiomotor neuron circuitry, their upcoming research will examine what happens when these circuits are wired in a different way, with neurons in the wrong spots. They’ll be looking at much subtler changes, Chandrasekhar said.
“If they don’t eat properly, do they move their jaw properly? That’s the next question that I want to answer,” said Emilia Asante, a doctoral candidate in the lab. “Are the axons not going to the right position? Are their neuromuscular junctions not properly positioned? Are there fewer of them in the mutant? There are all these questions that these assays are actually critical in answering.”
Asante is also working to make the feeding test more quantitative and less labor intensive. In its current form, someone has to look at each larva and judge if the food in its stomach makes it a zero, one, two or three. They want to be able to measure more accurately how much food is in the fish’s belly. If they were able to develop a faster and more accurate test, researchers would be able to rapidly measure food intake in a greater number of fish and to test the effects of many different chemical and environmental factors.
Zebrafish are a unique lab animal model used in research for a number of reasons. They’re easy to observe because the embryo develops quickly in an egg outside of the mother. They’re transparent, so researchers can make certain cells visible using florescence and observe them in a developing animal without killing it. Their genome is fully sequenced, so researchers can easily create mutations in specific genes using CRISPR technology.
“Many of the same circuitry that you find in humans are also there in more primitive organisms, and one of them happens to be the zebrafish,” Chandrasekhar said. “It has got some of the same types of neurons and the same types of circuits that you can find in humans.”
Research into the zebrafish’s neural networks can help researchers understand diseases like Amyotrophic Lateral Sclerosis, better known as Lou Gehrig’s disease, which causes a loss of function in a human’s motor abilities, including those of the branchiomotor neurons.
Donald Burke-Agüero stands in his office in Bond LSC, holding a model of an RNA protein structure. Burke-Agüero studies the bio-chemical functions of RNA, and how those functions might be able to be artificially designed or replicated. | Phillip Sitter, Bond LSC
By Samantha Kummerer | Bond LSC
“He’s a triple threat in science,” Bond Life Sciences researcher David Pintel said.
Donald Burke’s combination of scientific excellence, caring mentorship and devotion to the University of Missouri led Pintel to nominate Burke for the 2017 William H. Byler Distinguished Professor Award.
The university agreed, awarding him the honor in October.
The University-wide accolade recognizes a faculty member for their “outstanding abilities, performance, and character.” When Pintel read this description he said he instantly thought of Burke.
This is the first time a faculty member from Bond LSC has won the award. Pintel said the award shows the quality of people here and the department is proud of him for receiving it.
Burke is a Molecular Microbiology & Immunology professor. His lab in Bond LSC studies RNA, the molecule used to help cells copy genetic information from DNA.
For Burke, the award is an honor.
“You always try to do everything you can to contribute to making the place great and you don’t do it for the purpose of being recognized, yet when the recognition happens, it’s nice,” he said.
Burke’s lab hosts students from the high-school to post-doctoral level. For each member, Burke said he tries to figure out their motivation. He starts by just asking questions and is able to align their goals and his.
“You can’t just say ‘This is what we do in my lab, deal with it.’ You can’t do that,” Burke elaborated, “Yes, it’s a lot of work and a lot of effort, but it has ceased being a burden for me. Now, I think of it as a new fun challenge.”
He said that challenge has paid off because every student that has gone through his lab has taken his science in new directions.
Pintel said this connection Burke has with his students is easy to see.
“People in his lab love him and, to me, that’s always a good sign,” Pintel said. “When I see people in a lab like that, I know it’s a good environment. That always means something good is going on.”
During their time in his lab, Burke tries to teach his students the importance of working as a team as well as learning understand the research process.
“Some of the things I’m most proud of aren’t necessarily the most impactful research, but the things where I know the struggle that went into solving the puzzle that was in front of us,” he explained. “The thrill of the chase may not be as interesting to the rest of the world but you know how hard that person worked and how many false leads there were.”
Recently, Burke has expanded his passion for motivating others to a new area. In July, Burke became the Interim Chair of Molecular Microbiology & Immunology.
“Now that he’s the interim chair he is trying to provide the same kind of supportive environment for the department that he’s been doing for his lab,” Pintel said.
Burk said he wants to help other faculty members achieve their goals and prioritize tasks. He is also involved in a new faculty search where he works to ensure the applicant pool reflects those that might be wanting to apply by removing language that may prevent people from applying.
“Again, I want to help find what obstacles can be in their way and get rid of those before it slows them down,” Burke said restating his passion for helping others achieve excellence.
Donald Burke-Aguero is an MU professor in the Department of Molecular Microbiology & Immunology. He received his bachelors’ degree from the University of Kansas and his Ph.D. from the University of California, Berkeley. Burke joined the MU community in 2005.
