A step into summer research

DSC_3323.jpg

Jacqueline Ihnat, one of the 12 Cherng Summer Scholars, outside Dr. Cornelison’s lab at the Bond Life Sciences Center. | Photo by Mary Jane Rogers, Bond LSC

Sometimes the most learning occurs outside of the classroom.

For Jacqueline Ihnat, an opportunity to pursue research at the Bond Life Sciences Center this summer will give her that chance. She recently became one of 12 Cherng Summer Scholars, a full-time, ten-week program within the Honors College at MU.

“Doing research helps keep me focused on the bigger picture,” Ihnat said. “Sometimes in class we learn things that don’t seem entirely relevant or useful, but being part of a research lab allows me to apply some of the knowledge that I gain in the classroom.  It’s a daily reminder of why I’m learning what I am.”

Jacqueline Ihnat’s passion for science started in high school. Her high school biology teacher ignited that love by teaching her how to struggle through difficult problems and concepts. Now, Ihnat is an MU pre-med student with a major in business management and a minor in Spanish.

Since Ihnat is fascinated with cells and how our bodies function, she’ll be studying the role of specialized stem cells in muscle regeneration and how they interact with muscle fibers — specifically the role of Eph-A3, a type of cell-surface receptor. This project will take place in the lab of Dawn Cornelison, a Bond LSC biologist who will be mentoring Ihnat this summer.

DSC_3313.jpg

Jacqueline Ihnat as she pipettes samples in Dr. Cornelison’s lab in Bond LSC. | photo by Mary Jane Rogers, Bond LSC

Each muscle in the body is unique in its length, fiber organization and fiber type patterning, so Ihnat hopes to explore why two types of muscle — fast and slow twitch muscle — develop and regenerate to maintain each specific muscle fiber-type composition.

When a muscle is damaged from exercise or injury, a muscle’s stem cells, or “satellite cells,” will multiply, move towards the injury and form new muscle, replacing the damaged fiber. There is no research that determines if “fast” satellite cells create fast fibers and if “slow” satellite cells create slow fibers, and Ihnat hopes to tackle that question this summer. This kind of research gives scientists a deeper understanding of degenerative muscle diseases such as ALS, which could lead to more effective treatments and therapies.

The Cherng Summer Scholars program is supported by a gift from Andrew and Peggy Cherng and the Panda Charitable Foundation. The Cherng’s are the founders of Panda Express, a well-known restaurant chain. These scholarships support individually designed theoretical research, applied research or artistry projects under the mentorship of an MU faculty member.

For young scientists who are just starting to conduct research and struggling to feel successful, Ihnat has a few words of motivation.

“My high school biology teacher always said that research is 30 years of frustration and disappointment followed by 30 seconds of elation when you finally make a breakthrough,” she said. “Patience is key.”

The evolution of a corn geneticist

By Jennifer Lu |Bond LSC

DSC_2404.jpg

Paula McSteen is a professor of biological sciences at MU and a researcher at the Bond Life Sciences Center. | Photograph by Jennifer Lu, Bond LSC

When developmental plant geneticist Paula McSteen thinks about the specimens she studies, one word comes to mind: potential.

She thought it as she stood in the midst of the first corn field she ever planted as a post-doctoral fellow in corn genetics.

She thinks it as she counts kernels from corn crosses that will be sent to Hawaii, a hotspot for corn geneticists looking to add a second harvest to their research year.

And she sees it in the students she mentors as a professor of biological sciences at MU and a researcher at the Bond Life Sciences Center.

 

Embracing the corn

McSteen entered the field of corn genetics 21 years ago, as a post-doctoral fellow in Berkeley.

“What’s really amazing is that when you plant a field of corn, the field is just bare,” McSteen says.

“A few weeks later, you come back and your plants are this high,” she says, gesturing with her hands. “And a few weeks later, they’re this high. And a few weeks later, they’re massive and it’s all just coming from nothing. The instructions are there in the seeds, but otherwise the plant is taking nutrients and water from the soil and using the air and sun to generate sugar for growing. It’s amazing. You come back and you’ve got this whole field of corn.”

During her first corn season, McSteen remembers being surrounded as far as the eye can see by corn as tall as people. “I feel like that’s one reason why people get into corn. You’re not staring down into a microscope, you’re embracing it. It’s right there in front of you.”

The feeling hasn’t gone away.

“When I see my plants,” McSteen says, “I’m excited about what’s going on with them. What could be happening here? What’s the meaning of these results?”

McSteen, who is Irish, grew up far removed from the sunny cornfields she works in. As a child in Dublin, she wasn’t particular outdoorsy. When her family went camping by the sea over the summer holidays, McSteen spent most of her time reading books. Her favorite subject in school was science. By the time she sat for her high school leaving exam, her classes were mainly in geography, science or math.

“I’ve always been fascinated with genetics,” McSteen says. Ever since she learned about Punnett squares in high school, its puzzle-like quality has appealed to her. “I just loved that you could figure out what the prediction could be from a certain cross.”

She applied and was accepted to her top choice university, Trinity College Dublin, where she studied genetics. She went on to pursue a PhD in Norwich, England studying how snapdragons make flowers.

When it came time for her to do her post-doc, she had the choice to work on Arabidopsis, a popular plant model, or maize, a crop with many opportunities for research funding. She chose the latter. The decision changed the course of her career, from her research focus to her country of residence.

Corn brought her to California, Pennsylvania and then the University of Missouri, which has a long history of corn genetics.

DSC_2327.jpg

Researchers cross-pollinate corn by pouring pollen collected from the tassel over the ear. | Photograph by Jennifer Lu, Bond LSC

Everything we do starts with mutants

McSteen studies a part of corn plants called the meristem, which is filled with stem cells that become the reproductive organs of the plant: the tassel and the ears.

The tassel, where pollen is produced, is found at the top of the cornstalk, while the ears, which are the female reproductive organs, jut out from the sides. When and how they form depend on a growth hormone called auxin.

To understand auxin regulation, McSteen begins every summer with a field full of mutants. Each kernel contains a mutation, but it’s impossible to tell at first what is causing the mutation.

“To me, every single mutant is just potential. You can’t wait to find out what is mutated. You never know what you’re going to end up with.”

McSteen is interested in mutations that affect the tassels or ears. These plants produce ears with fewer kernels or tassels with fewer branches. Or they fail to make ears or tassels altogether. The defects are outward signs of problems in meristem development, and hint at disruptions to genes that are involved in how auxin is made, transported or perceived by the plant.

Once a mutant is identified, McSteen works backwards to find out which gene is causing the mutation, and where it is located on the chromosome. To date, her group has identified multiple genes related to auxin-mediated development, as well as two genes that affect the uptake or synthesis of essential nutrients.

A third project revolves around a strain of corn that produces half as many kernels as regular corn, causing it to look like grains such as rice or wheat. McSteen thinks that if they can understand what’s causing the shortfall in kernel development, it may be possible to engineer grains like rice and wheat to “double kernel” the way that corn does.

DSC_2251.jpg

Graduate student Eden Johnson photographs a mutant that has produced half as many rows of kernels. | Photograph by Jennifer Lu, Bond LSC

Ultimately, studying these genes help corn researchers to better understand plant development and improve yield.

You always love the organism

To keep all their experiments going, the McSteen lab plants three acres of corn every summer. Each acre contains 750 rows; each row holds 30 plants.

With the aid of a hand held planter, they drop 67,500 kernels into the soil. Then they do what McSteen calls a lopsided “planter’s shuffle” to stamp the soil down so that it covers every kernel.

“You can do a whole acre of corn in a few hours,” she said. “It’s hard work. You’re sore afterwards.”

During Missouri summers, temperatures can reach over 100 degrees Fahrenheit. It feels even hotter when it rains. The ground is either hard as a rock before it rains or so muddy after it rains that researchers have to take care not to wrench their ankles in the thick muck.

McSteen has worked on corn for so long that she’s developed severe allergies to corn pollen. It’s not uncommon among corn researchers, but her allergies prevent her from taking part in the pollination step that takes place at the height of summer.

“You’re out there in 100-degree heat getting the job done,” she says. “It’s a real bonding experience for the lab.”

To pollinate the corn, they slip paper bags over the ears and tassel of their plants. Covering the ears prevents accidental fertilization of the ears from stray pollen blown about by the wind. The bag over the tassel allows researchers to collect the yellow powder that will be used for controlled pollination.

“The next day, you bang the tassel and the pollen falls out into the bag,” McSteen says. “Then you gather it all up and you pour it on the ear.” It’s possible to pollinate about 100 plants in an hour, but you have to start early and work quickly, McSteen says. Otherwise, all the pollen is dead by noon.

McSteen’s allergies prevent her from shelling corn as well, but she’s on deck for planting and harvest time and all the other stages in between.

“If you’re a corn geneticist, you’re out there working with the plants. You always love the organism.”

DSC_2388.jpg

Paula McSteen labels the envelope of kernels from a corn cross that will be grown in Hawaii. | Photograph by Jennifer Lu, Bond LSC

A Collaborative Community

“To be a corn geneticist, you have to be very organized and plan ahead,” McSteen says. Because it takes a long time to grow several generations of corn, she’s only beginning to see the results of experiments she started years ago.

As a way to increase productivity, corn researchers send their seeds to warm places such as Mexico, Chile or Hawaii that can accommodate a winter harvest.

In the lab, McSteen chooses kernels from carefully selected mutants to ship to an island in Hawaii. There, a company will plant and harvest the corn for her, but she usually sends two of her researchers down to take care of the pollinations themselves.

McSteen counts out thirteen yellow kernels that are shiny and mold-free. “Potential,” she says, as she slips the seeds in an envelope with the cross information labeled on the front.

A three week trip to Hawaii in the winter isn’t as exotic as it sounds, says Eden Johnson, a third year graduate student in McSteen’s lab. On the island, the beaches are rocky and full of riptides. “It is literally cornfields, one diner and a stop sign. The whole island exists for corn.”

“When you’re down there in Hawaii, you hang out with the other researchers,” McSteen says. “If their field is peaking and your field is not, then you’ll go help.”

In her experience, the corn community tends to be collaborative rather than competitive. She suspects it’s because everyone recognizes that corn takes a long time to grow.

“If you find out you’re working on similar things, you’ll work together, divide the work and do it together,” McSteen says. Researchers don’t race each other to be the first one to publish. “They won’t do that because they have respect for how long it takes to grow the corn.”

DSC_2322.jpg

Katy Gurthrie removes a bag used to collect pollen from the tassel. | Photograph by Jennifer Lu, Bond LSC

Growing careers alongside corn

McSteen is as serious about mentorship as she is about corn. “It’s part of the job of being a professor”.

According to Katy Guthrie, a second year graduate student in the lab, McSteen takes a Goldilocks approach to managing her students.

Neither too hands on or too hands off, “it’s exactly what I need,” Guthrie says. “She’s kind of like my academic parent for the next five years.”

Back at Penn State, McSteen supervised a PhD student who was talented writer. “I noticed this and gave her opportunities to write.” McSteen introduced her to a science writer and encouraged her to spend a summer writing for a science publication. “Now she works for the National Academy of Sciences. I’m really proud of her, and I feel like she’ll have a big impact communicating science to the public.”

A post-doc wanted to do go into teaching, so McSteen invited her to co-teach her class. Her post-doc went on to become a teaching professor at Mizzou. Another student turned her research experience in mapping mutants in corn into a successful career at a corn company.

“I want to enable the people in my lab to reach their full potential,” McSteen says. “I always try to figure out what they want to do in the future and try and facilitate that.”

 

Small steps to treat neuromuscular disorder

Researchers find evidence of a genetic modifier that can improve symptoms of Spinal Muscular Atrophy

DSC_3243.jpg

Chris Lorson examines axons through a microscope. Lorson’s lab recently published results that showed evidence that the protein plastin 3 affects the severity of SMA. | Photo by Eleanor Hasenbeck, Bond LSC

Eleanor Hasenbeck | Bond Life Sciences Center

Two new potential treatments might improve the lives of patients living with Spinal Muscular Atrophy.

Researchers in the Lorson lab at Bond Life Sciences Center recently produced a new drug that increases the lifespans of mice with SMA, and they found evidence that an increased level of the protein plastin 3 lengthened life span and improved the animal’s nerve function.

Two genes impact Spinal Muscular Atrophy, SMN1 and SMN2. In a healthy body, SMN1 creates a protein called SMN that helps maintain motor neurons controlling muscle movement. If someone is born without SMN1, their body relies on SMN2 to produce this protein, but a small change in the SMN2 gene causes it to make much less of the protein than needed. This leads to SMA, a disorder where an individual loses motor and nervous function, often starting in childhood, over a number of years.

Although rare, sometimes siblings develop SMA, providing an unusual insight into SMA development. Discordant siblings — or siblings that both have SMA but have different severities of the disorder— suggest that other factors could contribute to SMA.

Researchers are investigating why this happens. One theory is that a “genetic modifier,” another gene or protein elsewhere in the DNA, impacts the severity of SMA. The protein plastin 3 could be this modifier.

Plastin 3 doesn’t improve the severe SMA mice, but extended the lives of mice with more mild cases of the disorder. The Lorson lab created its own SMA drug, an antisense oligonucleotide that allows SMN2 to produce a functional protein. The drug is capable of extending survival of SMA mice from approximately 13 days up to 150 days from a single treatment. The typical lifespan of a lab mouse is 1.3 to 3 years.

Kevin Kaifer, a graduate student in the Lorson lab, gave the SMA mice a low dose injection of the drug, increasing their lifespan to about 30 days. Then, they modified a gene in the mice to increase the level of plastin 3. Mice that received the drug and the plastin 3 therapy lived about 40% longer than mice that received only the drug.

Lorson said the results provide proof of concept that plastin 3 does not make more SMN, but actually decreased disease severity. The SMA mice showed improved neuromuscular junctions, the sites where nerve cells fire electrical impulses to the muscles in the body.

“That’s really where plastin 3 is designed to function, at the neuromuscular junction,” Lorson said. “So that brings the idea of plastin 3 full circle; it does not increase SMN, but it does improve the function of the nerve which is where plastin 3 is supposed to function normally.”

This discovery shows promise for a future treatment to some with the disease.

“SMA is a very broad clinical spectrum disease, so there are patients who have an incredibly severe form, and patients that don’t develop disease until adulthood,” said Chris Lorson, a Bond LSC scientist. “Perhaps one therapy is not going to address that very broad clinical spectrum, and you’re going to need to address different parts of the disease with different therapeutics.”

Despite it’s relative rarity as a disease, new treatments for SMA are hitting the market. In December, the Food and Drug Administration approved Spinraza, an antisense oligonucleotide similar to the drug the Lorson lab. But the infrequency of SMA means treatment comes at a cost: $750,000 for the first year of Spinraza and $375,000 for subsequent years. Spinraza is an FDA-designated orphan drug, meaning it’s a treatment for a disease that affects less than 200,000 people in the U.S. To incentivize research into rare diseases, The Orphan Drug Act allows pharmaceutical companies longer exclusive patent rights. Drugs that treat rare diseases that impact children, including Spinraza, can be allowed priority review, basically putting these drugs on a faster track from lab to market. Though the act has led to more research in certain diseases, it has sparked controversy as patients with no other treatment options are burdened with the resulting drugs’ high cost.

Still, it’s the first FDA approved treatment available to the 9,000 Americans living with SMA.

“I think collectively this is a very exciting time in the SMA field, whether we’re talking about SMN targeting compounds or drugs that are capable of augmenting function,” Lorson said.  “To have a rare disease that has so many shots on goals, so to speak is really exciting.”

“The SMA community is really a model for how foundations, families, patients and government agencies can come together,” Lorson said. He said families and government agencies are often in the same room as academics, biotechnology and pharmaceutical companies during meetings.

“The amount of support from the patients, the families and the non-profit world has really helped drive SMN research… I think that’s really helped push SMA from an unknown 20 years ago, to an approved drug.”

Christian Lorson is a professor of veterinary pathobiology at the Bond LSC. His research focuses on spinal muscular atrophy.
The results of this study were published in an article in JCI Insight, “Plastin-3 extends survival and reduces severity in mouse models of spinal muscular atrophy.” This work is partially funded by grants from the Muscular Dystrophy Association, FightSMA, the Gwendolyn Strong Foundation, and the Missouri Spinal Cord Injury/Disease Research Program. CureSMA provided the initial support for the development of the drug/antisense oligonucleotide used in these studies.

 

BPA rewires the sex of turtle brains

By Jinghong Chen | Bond Life Sciences Center

Turtle box 2.jpg

Painted turtle eggs were brought from a hatchery in Louisiana, candled to ensure embryo viability and then incubated at male-permissive temperatures in a bed of vermiculite. Those exposed to BPA developed deformities to testes that held female characteristics.Photo by Roger Meissen | © 2015 – MU Bond Life Sciences Center

Cool dudes, hot mommas. This is the underlying concept behind sex development in painted turtles, a species that lacks sex chromosomes.

A painted turtle’s sex is determined by temperature at which the eggs are incubated at critical stages during early development. Eggs incubated at lower temperatures produce male turtles, while those incubated at higher temperatures results in females.

However, early exposure to certain environmental chemicals that mimic hormones naturally produced in individuals can override incubation temperature. Scientists at the Bond Life Sciences Center have teamed up to study how endocrine disrupting chemicals (EDCs), namely bisphenol A (BPA) and ethinyl estradiol (EE), result in irreversible sexual programming of the brain in painted turtles.

“Turtles do not have sex chromosomes. Instead, they demonstrate temperature sex determination. But if they are exposed to EDCs prior to when certain organs form, such chemicals can cause partial to full sex reversal to female both in terms of the gonad and brain,” said Cheryl Rosenfeld, a Bond Life Sciences Center investigator and an associate professor of biomedical sciences at the University of Missouri. “The males will essentially act like females in terms of their behavioral responses.”

The hormones Rosenfeld refers to are BPA and EE, two widely used EDCs. BPA is present in many commonly used household, such as plastic food storage containers, store receipts, and dental fillings. The EE is present in birth control pills and can accumulate in many aquatic environments. These chemicals have been identified in all aquatic environments tested to date, including rivers and streams. Thus, exposure of turtles and other species that inhabit such environments can potentially lead to irreversible effects.

Previously, Rosenfeld and colleagues had studied how these chemicals change behavior of painted turtles after treating the eggs with BPA and EE under male-promoting temperatures. They discovered that male turtles that are early exposed to chemicals exhibit greater spatial navigational ability and improved memory, which are considered female-typical behaviors.

Rosenfeld and colleagues postulated that if the behavioral patterns differ between those exposed to BPA and those who were not, the different behaviors may be due to underlying and persistent differences in the neural circuitry between these two groups.

DSC_3253.jpg

Cheryl Rosenfeld is a Bond Life Sciences Center investigator and an associate professor of biomedical sciences at the University of Missouri. | photo by Jinghong Chen, Bond LSC

A gene map for turtle

In order to address this possibility, Rosenfeld teamed up with Scott Givan, associate director of the Informatics Research Core Facility, to study the gene expression profiles of the turtles and potentially identify patterns of gene expression associated with the altered behaviors.

After Rosenfeld’s team tested the behavior of the turtles, they collected RNA from the turtle brains to perform a technique called RNAseq that isolates all of the transcripts expressed in this organ. RNA is a nucleic acid that carries genetic information and is indicative of the expression level of every gene in the turtle genome. Once these sequencing results were obtained, Givan had to align the results to the painted turtle genome that has been previously sequenced and annotated. He then determined the transcripts that were differentially expressed in turtles developmentally exposed to BPA or EE versus those unexposed individuals.

There are no existing turtle gene pathway profiles. Therefore, Givan had to analyze the turtle gene expression profiles based on those previously identified in human samples.

“[One] of the most important things in this paper is the linkage of the gene expression profile to behavior difference,” Givan said. “But the gene and metabolic pathway data don’t exist for turtles. We had to basically infer pathway modeling based on the human metabolic pathway maps.”

DSC_3249.jpg

Scott Givan is the associate director of Informatics Research Core Facility and research assistant professor of molecular microbiology and immunology. | photo by Jinghong Chen, Bond LSC

The results suggest that BPA and, to a much lesser extent, EE exposure overridden incubation temperature and altered the gene expression profile in the brain to potentially reprogram brain to the female rather than male pathway. Specifically, BPA exposure was associated with metabolic pathway alterations involving mitochondria, such as oxidative phosphorylation and influenced ribosomal function.

Mitochondrial activity provides energy. Up-regulation of metabolic pathways in mitochondria can lead to more energy in brain cells, which may have permitted BPA-exposed turtles to demonstrate faster responses and greater cognitive flexibility, including enhanced spatial navigational ability that was previously identified in this group.

The other changes — oxidative phosphorylation and ribosomal function — play key roles in protein synthesis. Specifically, oxidative phosphorylation generates is one of main pathways involved in generating ATP, which is considered an energy source. Ribosome functions to assemble amino acids together for the synthesis of proteins, including enzymes that may facilitate metabolic reactions.

Less appealing males

The possibility for shifting brain sex has a real impact in the wild.

In the beginning, a turtle’s brain is neutral, as it is requires hormones to sculpt and direct it to be male or female. However EDCs, such as BPA and EE, can usurp these normal pathways and cause the brain of otherwise male turtles to develop more feminine characteristics.

“There are certain programmed behaviors [male turtles] have to do to entice the female to select them as their reproductive partner, but if he is not demonstrating these male-typical behaviors, she will likely reject him,” Rosenfeld said. “Even if such chemicals reprogram the brain and subsequent adult behaviors without affecting the gonad, it could have individual and population consequences by reducing a male’s likelihood of breeding.”

Combined with possible shrinking and already inbred population, declines in male turtles or skewing of sex ratio to females that could originate due to EDC-exposure, could push turtle species that exhibit temperature-dependent sex determination (TSD) to the brink of extinction.

“The concern also with turtle species that exhibit TSD, climate change and exposure to EDCs can lead to detrimental and irreversible imbalances in sex ratio favoring females over males, and thereby compromising genetic diversity of the population as a whole,” Rosenfeld said.

Future studies in Rosenfeld’s lab plan to extend the research to female turtles to learn whether the chemicals have any effects on females derived based on TSD rather than those due to exposure to environmental chemicals that are similar to estrogen. She also hopes to look into individual brain regions, such as the forebrain and hippocampus that are essential for cognitive abilities.

 

Cheryl Rosenfeld is a Bond LSC investigator,associate professor of biomedical sciences, and research faculty member in the Thompson Center for Autism and Neurobehavioral Disorders. Scott Givan is the associate director of Informatics Research Core Facility and research assistant professor of molecular microbiology and immunology.

This research was funded by the Mizzou Advantage Program, the Bond Life Sciences Center and the University of Missouri Office of Research.

Old friends, new ideas

A partnership between MU and Gyeongsang National University in South Korea has created lasting connections

By Eleanor Hasenbeck | Bond Life Sciences Center

DSC_9853.jpg

Discussion went global this week as researchers converged from Gyeongsang National University in South Korea, MU and Washington University at Bond Life Sciences Center for the sixth MU-GNU International Joint Symposium in Plant Biotechnology.

Plant biologists from each university shared their research, ranging from molecular biology and signaling to breeding soybeans for improved yields. The symposium is held every two years, alternating locations between the U.S. and South Korea. This conference marks the eleventh year of collaboration between GNU and MU.

“Every trip that comes over, new collaborations develop,” said Gary Stacey, a Bond LSC scientist of soybean biotechnology and chair of the symposium’s local organizing committee. “Just at dinner the other night, you could hear people talking and saying ‘We should do that together.’ You get people together and they collide, and good things come from that. The whole idea of these symposiums is try to increase those collisions.”

As those involved share new research and ideas, these collaborations create opportunities. A former student in Stacey’s lab recently received a doctoral degree from both universities as part of a joint-doctoral degree program. Undergraduate Korean students can also complete a “2+2” degree, where students can begin their studies with two years at GNU and finish with two years at MU.

The schools also exchange faculty members. GNU researchers Jong Chan Hong and Woo Sik Chung completed sabbaticals at MU. Stacey has spent time in Korea, and his lab receives funding from Korean grants.

“Getting our students to interact with Korean students and Korean faculty expands their horizons, gets them in contact with other cultures and is really part of creating an intellectual environment where students can grow,” Stacey said.

For Stacey, the symposium has also brought valued friendships. “After you’ve been over there, and you know these guys for eleven years, it’s like your cousin coming home,” he said. “You’re not a visitor anymore. You’re like part of the family.”

For more information about the science exchanged, visit http://staceylab.missouri.edu/symposium.

The next Martians: the common bean?

Researchers in the Mendoza-Cozatl lab grow beans in a soil that simulates Martian soil
By Eleanor C. Hasenbeck | Bond Life Sciences

As NASA works to send people to Mars, researchers at the Mendoza-Cozatl lab at Bond Life Sciences Center are exploring the possibility of sending beans to the red planet. The journey from Earth to Mars alone would take somewhere between 100 to 300 days. To feed astronauts on these longer missions, scientists are studying space horticulture.

Norma Castro, a research associate in the lab, studies how common beans grow in a soil that simulates Mars’ red soil. The common bean is a good candidate for interstellar cultivation. Beans are a very nutritious crop, and their affinity for nitrogen-fixing bacteria can improve soil health while requiring less fertilizer. Castro is trying to understand how different varieties of beans could grow in the soil.

“This kind of research not only will tell us the right plants to take to Mars, but also which kind of technology needs to be developed,” Castro said.

From neuroscience to negotiations

Neuroscientist and former Secretary of State science adviser to speak at Life Sciences Week
By Eleanor C. Hasenbeck | Bond Life Sciences

Frances Colon

Frances Colón has spent the past decade representing the United States all over the world on topics ranging from climate change to the advancement of women scientists. She will reflect on that experience in her talk at 3:30 p.m. Monday, April 11 in Monsanto Auditorium. | Photo courtesy of Frances Colón

A career in science doesn’t only mean working in a lab, and no one knows that better than Frances Colón.

Colón, a neuroscientist by training and policy maker by trade, will speak about how scientists can become more involved in policy without abandoning the laboratory bench.

During her Missouri Life Sciences Week lecture “My path to science citizenship,” Colón will talk about her transition from the lab to policy. She’ll speak 3:30 p.m. Monday, April 10, in Monsanto Auditorium.

“I think scientists need to realize that they have a broader set of skills than they give themselves credit for that can be applied to the service of the community and their country in many different ways,” said Colón. “I think we’re living in a time where our country needs scientists to get engaged at every level. That doesn’t mean they need to leave a career in academia to go into policy, but it could certainly mean involvement everywhere from the community level to the national level.”

After receiving a doctoral degree in neuroscience and studying how nerve cells mature at Brandeis University, Colón first got involved in making policy as an American Association for the Advancement of Sciences policy fellow. She then served as science and environment adviser for western hemisphere affairs for more than three years before she became deputy science and technology adviser to the Secretary of State, a position she served in until January.

As deputy science adviser, she led efforts to reengage Cuba in scientific collaboration after U.S. policy regarding Cuba shifted. She also coordinated climate change policy for the Energy and Climate Partnership of the Americas, and she worked to advance women and girls in science, technology, engineering and math. Today, she looks to use platforms outside of the government to accomplish the same missions.

Colón said of her career thus far, she is most proud of the work she’s done to educate women in opportunities in STEM careers.

“A lot of these countries started to realize that they can’t tackle a lot of the biggest challenges they’re confronting, from climate change to energy security, without having all of their best talent at the table. That required providing equal opportunity for women and men to achieve these positions,” Colón said. “We worked a lot on finding opportunities for girls to discover STEM careers and to help countries plan out what their STEM capacity building activities could be.”

These activities included things like the two-week camps for girls in South America and Africa, where they learned about coding and genetics with help from corporate partners.

Colón holds a doctorate from Brandeis University, and a bachelor’s degree in biology from the University of Puerto Rico. She was a delegate to the National Committee on U.S.-China Relations’ Young Leaders Forum, and a graduate of the National Hispana Leadership Institute. Last year, she was named one of the 20 most influential Latinos in technology by CNET en Español.

Colón will speak at 3:30 Monday, April 10 in Monsanto Auditorium as part of Missouri Life Sciences Week.

National Cancer Institute researcher to speak at Life Sciences Week

By Jinghong Chen | Bond Life Sciences Center

“Living things are too beautiful for there not to be a mathematics that describes them.”

Thomas D. Schneider will speak Tuesday, April 11 in Bond LSC’s Monsanto Auditorium. | Photo by National Institutes of Health

Thomas D. Schneider will speak Tuesday, April 11 in Bond LSC’s Monsanto Auditorium. | Photo by National Institutes of Health

This is Thomas Schneider’s motto.

Schneider, a research biologist at the National Cancer Institute, spent most of his career understanding math and its relation with fundamental biology. His lab focuses on the DNA and RNA patterns that characterize genetic control systems; they invented the widely-used sequence logos.

“In the first place, I am doing this because I am curious,” Schneider said. “Let’s go find the math and who knows what would come out of that.”

Schneider will speak during the 33rd annual Missouri Life Sciences Week, a celebration of MU’s science research and collaboration across disciplines.

Claude Shannon’s information theory lays the foundation of Schneider’s study. In the landmark paper published in 1948, Shannon defined the quantity of information and how it transmits amid interference of noise. When people communicate via a phone call, the heat of the telephone line is one type of noise. As noise contaminates information, the highest rate at which information can be reliably transmitted over a noisy communication channel is defined as the channel capacity.

A similar concept emerges in Schneider’s Molecular Information Theory. It leads to a theoretical measure of the efficiency of molecules.

“I thought [Shannon’s] theory was screaming as I dragged it into biology. The stunning thing is that it fits biology really, really well,” Schneider said.

He looked at the DNA binding protein EcoRI, a restriction enzyme that binds DNA. When it binds, there is an inequality relationship between information and the information gained for the dissipated energy. The efficiency of DNA binding sites on nucleic acids is about 70 percent.

This mysterious number has appeared widely in his research and it also describes ecological evenness. In an even ecosystem with all species being equally represented, the evenness is close to 100 percent, but when only one species dominates the environment, its evenness dwindles to 0 percent.

Schneider found that fish species diversity in a Georgia estuary is near 70 percent and the evenness of plant species in different divisions of 8-square-meter plots in California is also around 70 percent.

When Schneider turns from ecological system to biological systems, this number still stands out. Caenorhabditis elegans (C. elegans), a free-living tiny worm, has been extensively studied and has had its entire cell lineage traced. On the basis of previous studies, Schneider calculated the efficiency of its lineage and found that the number fits the ubiquitous 70 percent, when excluding the dead cells of a C. elegans.

With this established case, one of his colleagues suggested looking into one of human’s biggest enemy – cancer. Cancer occurs when a cell develops mutations and grows out of control. Schneider hypothesized that if you have more of a certain type of cell, then you have a larger chance for that cell type to get a mutation that might lead to cancer.

The International Agency for Research on Cancer (IARC) publishes a report on all different types of cancers observed each five or six years. Based on the data collected by IARC and the hypothesis, Schneider found that for adults whose ages are above 14 years old, the cancer type evenness always remains around 70 percent.

“The thing that is interesting is that when you understand things fundamentally, it inevitably leads to practical results,” Schneider said.

Schneider’s speech on “Three Principles of Biological States: Ecology and Cancer” will be held at 1:15 p.m. April 11 in the Monsanto Auditorium at Bond Life Sciences Center.

Missouri Life Sciences Week is a university-wide event that brings together research across scientific disciplines at Mizzou. This year will highlight more than 300 student, faculty and staff research presentations and four topical lectures by accomplished researchers in addition to career development workshops and scientific service and supply exhibits.

Check out the full schedule of events here.

 

Hanson to explain why broken metabolites matter at Life Sciences Week

By Jinghong Chen | Bond Life Sciences Center

Andrew Hanson, right, will speak Friday, April 14 in Bond LSC's Monsanto Auditorium as the 2017 Dr. Charles W Gehrke speaker. | Photo by University of Florida, Institute of Food and Agricultural Sciences

Andrew Hanson, right, will speak Friday, April 14 in Bond LSC’s Monsanto Auditorium as the 2017 Dr. Charles W Gehrke speaker. | Photo by University of Florida, Institute of Food and Agricultural Sciences

People often think of metabolism as a perfect network. But that assumption is simply not accurate.

Andrew Hanson, an eminent scholar and professor at the University of Florida, describes the misunderstanding as “the power of a paradigm.” American biochemist Albert Lehninger spread the misunderstanding in his classic textbook “Biochemistry”, in which the message he communicated to generations of students was: metabolism is a beautiful machine that functions flawlessly.

Hanson challenges this “metabolism is perfect” paradigm using illustrations from different kinds of organisms in his lecture. He will speak in Bond LSC’s Monsanto Auditorium at 1 p.m. Friday April 14, during the 33rd annual Missouri Life Sciences Week.

For every living organism, metabolism is the sum of every chemical reaction that occurs to maintain life. This sum contains all the metabolites — small molecules created at each level of cell processes and final products — that share a part in the growth, development, reproduction and running of cells and whole organisms.

However, enzymes can make mistakes; many chemical compounds in cells are unstable and undergo spontaneous reactions. The consequences of enzyme errors and chemical side-reactions are, at best, unwanted and sometimes toxic, so organisms have developed mechanisms – damage-control systems – to deal with the consequences of damage.

Hanson’s lab has studied metabolite damage and the damage-control systems that plants and microorganisms employ to cope. But the impact of metabolic problems also reaches into the human domain, causing disease from failure or mutation of damage repair enzymes. “It matters in aging humans and animals a great deal, because aging is the result of cumulative damage,” Hanson said.

Plants are also afflicted by metabolite damage. Under environmental stress such as high temperature or water loss, the error rate of enzymes and rates of unwanted chemical reactions can go up.

The understanding of metabolite damage could also advance metabolic engineering, which is a purposeful manipulation by combining metabolic pathways and DNA techniques to produce desired products. After creating new pathways in an organism, it may fail to cope with the abnormal reactions produced by the new pathways. To fix the problem, the only solution might be to install the required damage control enzymes.

Hanson’s lab hopes to identify new or unsuspected damage reactions, and enzymes that repair or prevent damage. They also are working to connect with metabolic engineering groups that install modified pathways in plants and microbes to study sources of damage and propose solutions.

Metabolism is not perfect. However, after studying its imperfection for years, Hanson concluded, “life is put together in a very beautiful and even more powerful way than we first realize. It makes a lot of mistakes, but it also fixes them so well that we do not even notice them.”

Hanson’s lecture on “Fixing or safely trashing broken metabolites and why it matters” is this year’s Charles W. Gehrke distinguished lecture. Gehrke, a longtime MU professor of Biochemistry, was selected by NASA to analyze rocks retrieved from the first moon landing for any traces of extraterrestrial life. He died in 2009.

Hanson’s lecture is free and open to the public as part of Missouri Life Sciences Week. It occurs at 1:00 on Friday, April 14 in Bond LSC’s Monsanto Auditorium. See more about events during the week at bondlsc.missouri.edu/life-sciences-week.

Why self-defense turns self-attack

By Jinghong Chen | Bond Life Sciences Center

DSC_2816.jpg

Mahmoud Khalafalla, a Ph.D. student at Weisman’s lab, is isolating RNA from salivary glands of Sjögren’s syndrome mouse model to look for the expression of pro-inflammatory genes. | photo by Jinghong Chen, Bond LSC

Our immune system is often the key to our health. Everyday, it works to protect us from foreign invaders such as bacteria and virus, but what happens when it attacks our own tissues?

Gary Weisman, a Curator’s Distinguished Professor of Biochemistry at the Bond Life Sciences Center, is working to advance our understanding of the mechanisms behind immune system function and autoimmune diseases such as Sjögren’s syndrome.

In our immune system, B cells are responsible for producing antibodies to recognize foreign invaders. However, in many autoimmune diseases, B cells produce autoantibodies that recognize our own proteins, causing inflammation and tissue damage. In Sjögren’s syndrome (SS), they attack the glands that produce saliva and tears.

Patients with SS often suffer chronic dry eyes and dry mouth, which might lead to bacterial infection, difficulties in swallowing and speech.

“The symptoms decrease the quality of life rather than the length of life,” said Lucas Woods, research lab manager in Weisman’s lab.

Although SS patients are at higher risk of developing lymphoma cancers and other concurrent autoimmune diseases that may increase mortality, Woods further explained.

According to the Sjögren’s Syndrome Foundation, there are an estimated four million people living with the disease in the U.S. For unknown reasons, 90 percent of them are female.

Yet, current clinical treatments only reduce symptoms by using artificial saliva and tears or cholinergic agents to promote fluid secretion, but there is no approved treatment to reduce the inflammation of the glands themselves. This is the focus of Weisman’s lab.

Sensor of danger

There are 15 different types of nucleotide receptors in humans that regulate numerous cell processes from inflammatory responses to tissue regeneration. Those receptors are stimulated by nucleotides such as ATP. In the past three and a half years, Mahmoud Khalafalla, a Ph.D. student in Weisman’s lab, has focused on one of them in particular – the P2X7 receptor.

Previous studies show increased P2X7 expression in salivary glands from SS patients, as compared to healthy individuals. To understand the reasons behind this, Weisman’s lab used genetically modified mice that develop disease traits similar to SS patients.

In this mouse model, Sjögren’s-like disease occurs when the immune cells invade salivary glands and damage the tissue, leading to decreased saliva production. The invasion of immune cells is triggered by proinflammatory cytokines, a type of signaling molecule that promotes the recruitment of immune cells to the inflamed areas.

But what induces those cytokines?

Weisman’s lab tries to piece together the answer. For the first time, they found that the P2X7 receptor is responsible for the release of these proinflammatory molecules from salivary gland epithelial cells.

To function, most cell-surface receptors require ligands that bind to the receptor to induce cellular responses. The ligand for the P2X7 receptor is ATP – the “energy currency inside of cells.” P2X7 receptors are activated when high concentrations of ATP are released to the outside of the cells, which typically occurs when the cells are injured during inflammation.

“P2X7 receptors [act like] the sensor of danger,” Khalafalla said.

After identifying the role of the P2X7 receptor, the lab then asked: if we stop its activation, what would happen?

Using a drug that inhibits P2X7 receptor activation, they blocked the receptor in their SS mouse model to determine its effect on the development of autoimmune disease. Interestingly, saliva secretion was restored when the P2X7 receptor is blocked while the levels of invading immune cells in salivary glands were dramatically reduced.

“This gives us the thought that [blockade of the] P2X7 receptor is really a promising strategy to reduce salivary inflammation. This may not only relate to Sjögren’s syndrome, but to other autoimmune diseases as well,” Khalafalla said.

Our receptor

Another similar receptor that plays a role in autoimmune diseases is the P2Y2 receptor, which has been referred to as “our receptor” by Weisman’s lab.

As one of the researchers who proved the existence of this receptor, Weisman has spent most of his career studying it.

One of his research projects investigating P2Y2 receptors in human disease recently gained a grant extension for another five years from the National Institutes of Health. The lab found that in a mouse model of SS, similar to the P2X7 receptor, the expression of P2Y2 receptors was increased in both the salivary gland epithelial cells and immune cells.

Furthermore, after they knocked out the P2Y2 receptor in the SS mouse model by breeding them with genetically-modified P2Y2 receptor knockout mice, the inflammation of salivary glands was dramatically reduced.

“The very next step is that we are going to isolate these immune cells out of the diseased mouse salivary glands, and characterize what kinds of cells they are. We want to know exactly which ones are controlling the development of autoimmune diseases, and how P2Y2 receptors and nucleotides like ATP in general are contributing to the diseases,” Woods said.

 

Gary Weisman is a Curator’s Distinguished Professor of Biochemistry at the Bond Life Sciences Center. His research focuses on the relationship between inflammatory diseases and nucleotide receptors. He currently works on a collaborative research project with Dr. Carisa Petris, an eye surgeon at the MU Hospital, to understand the mechanism of how Sjögren’s syndrome damages the tear-secreting lacrimal glands in mice.