Dean Bergstrom, the new building manager for Bond LSC. | Photo by Mary Jane Rogers, Bond LSC
By Mary Jane Rogers | Bond LSC
“#IAmScience because I provide the world class scientists of Mizzou’s Bond Life Sciences Center with the finest facilities available.”
As the new building manager for the Bond Life Sciences Center, Dean Bergstrom makes it possible for everyone else to focus on his or her research. He’s worked in Bond LSC for nine and a half years as a research technician, and in Tucker Hall eleven years before that. His unique science background and hands on knowledge of this building means that he knows exactly what scientists need to complete their projects. A facility with such diverse research interests as Bond LSC might seem overwhelming to manage, but Dean is eager to tackle the challenge.
“My background as a technician means I’m the perfect person to step into this role,” he said.
Researchers find evidence of a genetic modifier that can improve symptoms of Spinal Muscular Atrophy
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.
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.
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.”
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.
A partnership between MU and Gyeongsang National University in South Korea has created lasting connections
By Eleanor Hasenbeck | Bond Life Sciences Center
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.
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.
Erica Majumder, a biochemistry Ph.D candidate. | photo by Mary Jane Rogers, Bond LSC
By Mary Jane Rogers | Bond LSC
“#IAmScience because I am endlessly curious and the world needs scientific solutions to our grand challenges.”
That is the attitude of someone who does her research with a purpose. Since the age of 14, Erica knew she wanted to pursue a degree in chemistry. Today, she uses that passion to research how anaerobic bacteria interact with uranium; essentially asking the question, “How do microbes and metals interact?”
What’s her end game? Improved health of the environment.
Neuroscientist and former Secretary of State science adviser to speak at Life Sciences Week
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
By Eleanor C. Hasenbeck | Bond Life Sciences
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.
Sheryl Koenig, the Grant Proposal Manager at Bond LSC. | photo by Mary Jane Rogers, Bond LSC
By Mary Jane Rogers | Bond LSC
“#IAmScience because I need to connect the dots. How do all the puzzle pieces fit together? Why do things do what they do? How can I apply that to other things?”
For Sheryl Koenig, science communication is an enormous part of her daily tasks. She works with researchers and scientists during the grant proposal process to translate technical scientific concepts into persuasive and relevant content. Why? So that those scientists can access the means to expand their #MizzouResearch and make exciting breakthroughs. Sheryl literally helps turn their ideas and dreams into reality! #scicomm
“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
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.
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.
