Being the youngest person in the lab has opened the eyes of this English, German and Croatian speaking undergrad.
Research was not always on senior Gabriela Akrap’s mind, until Ruthie Angelovici told her to apply for REU (Research Experience for undergrads). Being accepted started two months in Angelovici’s lab this summer that expanded Akrap’s science experience.
Akrap first was intimidated at first since she was younger that others in the lab, but soon came to feel comfortable.
“There’s so much information and so many different projects going on it’s sort of hard to grasp the general idea of what is happening,” Akrap said. “Once I got over that fear, everyone was and is so helpful. I couldn’t pick better people to work with.”
Akrap currently studies Biology and German, but is still exploring what she wants to do in the future. Being in the lab has given her a new perspective on a possible science career.
“It’s so important to get the truth and to get the truth out there,” Akrap said. “I believe in science for the greater good and it’s something I want to be a part of. You meet so many people that will help you with your future, everyone is so friendly in the labs because they love science so much. They pass the passion down to you and you start to have that passion in science.”
Akrap will either pursue med school or graduate school, a choice yet to be made. Akrap has always wanted to be a pediatrician.
“I think kids are so important,” Akrap said. “It’s important to educate the future generation, they are our future.”
The research Akrap does plays into her desire to help others. She is currently studying the amino acid composition in seeds.
“According to the world food program one in three people are malnourished,” Akrap said. “That’s probably due to the fact most of their diet is seeds, and most seeds lack several essential amino acids that your body needs.”
The goal is to understand the genetic regulation of these amino acids composition in the seed.
“You have 20 amino acids that make up every protein in your body,” Akrap said. “Some people might say they are the building blocks of life. My lab’s overarching goal is to make seeds more nutritious, meaning more nutritious food.”
Akrap wishes to solve the energy crisis as well as the food crisis.
From asking her mom ‘a bajillion questions’ growing up to now, Akrap’s fire for science has been maintained through moments in the lab.
“The cool thing about science is it’s absolute, in the end you can’t argue with facts,” Akrap said. “When I actually got results for the first time I was like this is so cool, science is so neat. A lot of things can go wrong, but once it actually works you have that little eureka moment.”
It takes a lot to move a discovery from lab bench to an application that can provide therapeutic benefits to those suffering from disease.
Bond LSC’s Chris Lorson is making moves to bridge that gap with the start of Shift Pharmaceuticals. With its formation in March 2017, Lorson adds co-founder and Chief Science Officer of the company to his list of titles that include Bond LSC investigator, professor of veterinary pathobiology and associate dean for research and graduate studies.
Shift Pharmaceuticals builds off of years of progress the Lorson Lab has made in understanding spinal muscular atrophy (SMA), which is the leading genetic cause of infant deaths. The disease causes neurons to die, leading to muscle failure, including those that affect walking, arm movement, and respiratory function. While SMA is technically a rare disease, it is remarkably common, affecting nearly 1/10,000 births.
“It’s a devastating disease for patients and families; while the primary defect in is nerves, this leads to problems in muscles, bones, and other vital systems,” Lorson said. “Historically, the majority of kids who develop SMA do not survive beyond 3-5 years.”
Lorson knew his research had potential for drug development, and MU’s Office of Technology Management & Industry Relations (OTMIR) pursued patent protection for the technology. This process helps safeguard the innovations resulting from the research and allows MU to better attract commercial interest to develop and market medical treatments originating from the technology. But it took a partnership with co-founder Steve O’Connor to get the ball rolling. O’Connor is MU’s Entrepreneur in Residence and has significant experience in starting drug development businesses and now serves as CEO of Shift.
“I never knew how to start a company,” Lorson said. “I would argue most academics don’t – this isn’t part of our traditional training. I sat around not knowing what to do, realizing I had this thing that could do a lot, but the practical steps of setting up a biotech start-up were beyond me.”
“Steve thought this technology sounded really cool, so in late March he submitted paperwork and by the end of March we were a company. Shift’s first grant was submitted 3 days later.”
The goal of Shift Pharmaceuticals is to move their lead compound into the clinic for SMA.
“When you look at the disease, it’s not just one cell type and not just one clinical type of patient,” Lorson said. “It really is a disease that is complex and the idea is to bring more options to the fight.”
With the start of any new business, money is always a necessity. Funding from the advocacy group CURE SMA provided the initial funding for the discovery of this compound, while several other foundations including FightSMA, the Gwendolyn Strong Foundation, and Muscular Dystrophy Association have further contributed to the pre-clinical development. MU’s OTMIR negotiated an option agreement with Shift, giving them the exclusive rights to the technology, which helped them obtain a recent $2.73 million grant from the Department of Defense Congressionally Directed Medical Research Program (CDMRP). This will move the company toward the first phase of investigating a new drug.
The root of SMA
Lorson has spent most of his scientific career chasing the underlying causes of SMA.
That search focused in on a few key genes in those suffering from the disease. Two genes — named survival motor neuron-1 and -2 (SMN1 and SMN2, respectively) — are central to SMA development. In patients, SMN1 is mutated and doesn’t process enough of a key protein (SMN) that helps neurons function. While SMN2 acts as a backup gene for this function, a miniscule change in the SMN2 gene causes it to make less SMN protein than required by the body.
In 2016, the Lorson Lab at Bond LSC produced a compound that increases the lifespan of SMA mice . They targeted the back-up gene, SMN2, to produce more functional protein and discovered an increase of protein causing a significant lifespan extension in treated mice. This discovery showed promise for creating a cure for those with SMA.
Shift Pharmaceuticals will be working on developing a drug that builds off Lorson’s work and targets all forms of SMA.
Shift’s first two employees, Mizzou alumnus Paul Morcos and UMKC alumnae Diane Beatty, will help move toward that goal. With Morcos in research and development and Beatty negotiating regulatory affairs, the company hopes to move the drug toward FDA approval.
Thanks to the recent Department of Defense grant, the next step looks to testing in larger animals and at things Lorson did not consider before.
“The experiments we will be doing are not academic in nature, rather, they are focused on the singular goal of preparing our lead compound for an FDA submission. From a traditional academic lab perspective, these might sound rather boring,” Lorson said. “All of these things are not things you do in an academic setting, but that is exactly the point. This is drug development, not the quest for another paper.”
Within the Business Incubator, MU will provide space for the company as well for their research. This sort of partnership is just another part that may one day help translate vital basic research into future treatment.
“Almost everybody has the possibility of doing something that is translational, it is just envisioning it in a different way,” Lorson said.
Cheryl Rosenfeld recently worked with the FDA to study genetic effects of BPA. Her results were published in Epigenetics in July 2018. photo by Roger Meissen | Bond LSC
By Roger Meissen | Bond LSC
After a decade of work, Cheryl Rosenfeld is no stranger to bisphenol A (BPA), and her most recent study challenges the dangers posed by developmental exposure the chemical.
Her results continue to raise concerns about how BPA can potentially turn on or off genes in animals and subsequent effects on that early exposure can have on the development and brains of rats. Their research was published in the journal Epigenetics in July.
Rosenfeld and the University of Missouri joined experts from University of Cincinnati and FDA researchers as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity, or CLARITY-BPA Consortium project. This collaboration is one of several across the United States meant to judge the chemical’s effect using standardized protocols established by the FDA to determine whether BPA exposure, especially during perinatal life, leads harmful effects.
“This is the first study published since a February 2018 BPA statement that challenges the FDA assertion that there is no concern for BPA,” Rosenfeld said. “We’ve shown using the FDA models and studies done right there at their facility that, indeed, early life exposure to BPA can result in gene expression and epigenetic changes that persist into adulthood.”
The study looked at gene expression changes in two brain regions — the hippocampus and the hypothalamus. The hippocampus is associated with long-term learning and memory and the hypothalamus plays a large role in hormone production that influence both the endocrine and nervous systems and affects diverse behaviors, including socialization, sexual behaviors, and appetite control.
Partners at the FDA/National Center for Toxicological Research fed Sprague-Dawley groups of rats — a standardized animal model in this research — diets of BPA, the synthetic estrogen present in birth control pills, ethinyl estradiol, or a chemical-free diet during a developmental period.
The brains from these animals were sent to Rosenfeld’s laboratory, who took biopsies from specific regions of the brain. They used these samples to evaluate whether a group of 10 genes, shown to be affected by BPA exposure in other studies, was affected by this exposure. They also examined the DNA methylation patterns for the promoters of three of these genes to determine whether prior BPA exposure led to persistent epigenetic changes. Epigenetic modifications do not affect the DNA sequence itself but gene and/or eventual protein expression.
Investigators determined that for several of the genes examined BPA exposure altered the expression pattern relative to animals not exposed to either chemical. Sex differences in gene expression in these two brain regions exists in normal animals, and such differences might thus contribute to masculinization or feminization of the brain manifesting as differences in various behavioral patterns, such as male or female sexual behavior. However, previous exposure to BPA abolished many of these gene expression differences between males and females, suggesting that it could disrupt male- and female-typical behaviors. For a gene, brain derived neural factor (BDNF), involved in learning and memory, BPA exposure led to increased methylation of its promoter, which could affect the expression of this key gene. Hippocampal expression of several genes was associated with prior performance in a test designed to measure learning and memory.
“It has become increasingly apparent that BPA can act as a weak estrogen, but what we’re seeing in these results is that it can elicit other effects in addition to those mirroring estrogen and likely independent of estrogen receptor pathways,” Rosenfeld said.
Initiatives like this and other CLARITY-BPA studies aim to answer questions that may later inform government regulators on how to limit or balance the health effects of manufactured chemicals that end up in the environment and may affect human and animal growth in previously unknown ways. With more than 15 billion pounds of BPA were estimated to be produced in 2013, its ubiquitous use in making plastics, lining cans and other manufacturing is of concern. Rosenfeld hopes a closer look at its epigenetic effects may lead to better regulation of the chemical.
“When people are thinking about the effects of BPA, they need to be thinking about it on a molecular scale,” she said. “These results might be subtle, but they can lead to dramatic consequences with long-standing, irreversible changes. Once BPA exposure resculpts an animal’s brain through DNA methylation and other epigenetic changes, it may be permanent.”
One class changed senior K’Imani Davis’s mind, who is now going into her senior year working in the Anand Chandrasekhar lab at Bond LSC.
“I used to actually hate science, and when I say hate, I hated it,” Davis said. “Senior year of high school I took AP Bio, I loved it. I don’t know what happened, but I started to try and I liked the subject.”
After Davis’s change of heart, she decided to start out at MU as a biology major, and she is now going the pre-med route.
Just like Davis ended up in science, she ended up at MU by chance.
“I wasn’t going to come here at first,” Davis said. “I never visited and never knew someone here. I was so indecisive about my college decisions so I put all my options in a hat and just drew, I drew Mizzou so I just came here.”
Davis came to MU knowing nothing about the campus, programs or any students. And then she stumbled across an opportunity that changed her college experience for her.
“I actually got involved by accident,” Davis said. “I had a class in this building and across from my class was the undergraduate research office. I decided I wanted to do research because it was science out of the classroom.”
From freshman year to now, Davis has found a home away from home in her lab.
“I think of my lab as a family,” Davis said. “We always have something to do all together every semester. It’s very family oriented, it’s very close and tight knit. My boss sometimes even acts like my father.”
Davis didn’t just find a family at Bond LSC, she found her passion. The lab is studying neuronal migration in zebra fish. This study looks at how neurons move into place as the brain and nervous system develops with the hope of learning how the process works and using that information to understand neuro-degenerative disease. In her freshman year when Davis was an intern in the lab, she fed the fish and cleaned the tanks. Now, she analyzes fish behaviors and compares swim patterns between wild and mutated zebra fish.
“By analyzing their behavior, we are able to see if there are neuronal migration patterns, and we see what defects leads to different behaviors,” Davis said.
Davis’s goal for this upcoming year is to have a poster of her research to display to others. Her experience at MU has brought her a family, a passion and no longer a hatred for science.
“I think everything happens for a reason,” Davis said.
A chance encounter brought Katalin Toth to Mizzou.
The postdoctoral fellow, first heard about MU when Gary Stacey visited University of Munich. Toth heard of a position opening up in his lab. She has now been in the Stacey Lab for six years.
“I knew his work was important and well known,” Toth said. “You can almost directly apply what you find on soybeans to agriculture.”
Science has led Toth from the mountains of Slovakia where she did her masters to Hungary for her Ph.D. and Germany for research. Missouri ended up being the next step in her journey.
Being a foreign postdoc in the lab gives Toth a unique perspective. She has seen two different research environments — one in Europe and the other here —that highlight cultural and experimental differences.
“Here you have a facility core and you have to pay for it,” Toth said. “You have to really consider what you are doing and how you design your experiment. It is actually good because you really have to think about how you use your time in your experiment.”
Toth has always been given opportunities in the labs she has worked at, but as a postdoc she now has a chance to express her love for science to others.
“As a postdoc here, I get the opportunity to be involved in tasks not related to the everyday life of a researcher,” Toth said. “From organizing outreach activities to promoting plant science, it is important to me that people understand the importance of science.”
Toth’s love for science sprouts from the exploration of soybean research and how it will affect our world and other cultures. Currently, she is studying soybean association with beneficial soil bacteria that help soybeans to better access nutrients such as nitrogen, vital for a crop’s growth.
“There are different bacteria in the soil and I am looking at how the plant’s immune system is responding to the beneficial bacteria.”
Toth’s travels have also opened up her perspective on different culture’s needs.
“I care about the environment and doing something that is useful like this for agriculture, hopefully will help the environment,” Toth said. “After I saw how local people take care of Amazon while traveling in Peru, for example, I want my research to help improve crops and make an impact on the environment in a different way.”
Toth has done research for 10 years, and doesn’t want to stop anytime soon. From long hours at the lab to even weekends of research, Toth is always eager.
“Everyday there is something more exciting,” Toth said.
As busy as she is, Toth has always found time to enjoy her favorite place: outdoors. However, there is only one slight fall back from her move to Missouri.
“I just do not like the hot summers here,” Toth said.
MARC/IMSD Director Brian Booton poses with the 2018 MARC/IMSD fellows. photo by Roger Meissen | Bond LSC
By Allison Scott | Bond LSC
Research at the undergraduate level offers more than meets the eye. With students from every year of their undergraduate careers working in Bond LSC, it’s a great opportunity to acquire skills and experience.
Linda Blockus, head of the Undergraduate Research office in 150 Bond LSC, advises students to get started early and be proactive.
“I encourage students who are interested in research to talk to people and network,” Blockus said. “Talk to your professors, advisors and other students to find out what is available. Then, pursue those opportunities.”
It isn’t all as intimidating as it might appear. Students have a number of resources available to find out more about research on campus.
“There’s no one way to get involved,” Blockus said. “Students can go directly through our website, undergradresearch.missouri.edu, come to our office or go to their professors.”
That’s exactly what students involved in the Freshman Research in Plant Sciences (FRIPS) program have done. Sarah Unruh, a Ph.D. student who serves as a Graduate Student Coordinator for the program, boasts of the program’s ability to guide research-minded students along their path at Bond LSC.
“They do 10 hours of research in lab,” Unruh said. “We try to give them skills that are helpful moving forward, so things like finding papers and keeping up with a lab notebook.”
Each of the students selected for the program works in a lab they find the most interesting, but the program assists with those relationships to help students adjust to the process.
“Students lead the way in which lab they go to,” Unruh said. “They interview with different faculty, but we facilitate the match-making.”
Those interactions and networking opportunities open doors down the line.
“I think what they get the most out of FRIPS is that they’re actually doing science, so they get an idea of what it looks like,” Unruh said. “They’re making connections on a different level than just the classroom with teaching assistants and professors.”
Jenna Bohler — one of the students involved in FRIPS this year — has benefited from its connection-facilitating.
“Paula McSteen, Norman Best and Jenn Brown have taught me so much this year in particular,” Bohler said. “They’ve been great resources whenever I’ve had questions.”
Bohler is about to finish her FRIPS experience and can attest to the program’s influence on her first year at Mizzou.
“I knew coming into college I wanted to be involved in research, and FRIPS allowed me to get involved really early so I have four years instead of two or three,” Bohler said.
And it’s not only helpful in the lab.
“What I’ve learned from FRIPS has helped with my classes,” Bohler said. “I learn things before I’m taught them in class, which makes them easier to understand.”
Some FRIPS students have even extended their research opportunities beyond their freshman year.
“Students have used their time wisely in the lab and then gone on to do summer research programs,” Unruh said.
For those who aren’t freshman but find themselves interested in research, there are a number of programs available.
The Society of Undergraduate Researchers in Life Sciences (SURLS) is a group of undergraduate researchers who meet twice a month to explore the options they have within their field. It helps participants to network, meet people with similar interests and better understand a number of components of research.
Alec Wilken, a junior bioscience major who works in the Holliday lab in the medical school, served as the vice president and will be the president for his senior year. He’s been part of SURLS since he was a freshman and has seen first-hand how it’s shaped his path in the field of research.
“SURLS helped me find what I was interested in,” Wilken said. “We have professors come in, and we visit labs, which helps undergraduates grasp how interesting research on campus really is.”
SURLS provides students with the opportunity to grow throughout their undergraduate careers.
“I stayed in SURLS after joining my lab because it became a vehicle that helped me be better in my lab,” Wilken said.
The organization’s impact has allowed Wilken to uncover the path he wants his career to take, as he now plans to earn a Ph.D.
“I found a home in research, and SURLS helped me do that,” Wilken said.
For those with plans to pursue a Ph.D. in their future, MU’s Maximizing Access to Research Careers/Initiative for Maximizing Student Diversity (MARC/IMSD) program is the perfect fit.
The grant is funded by the National Institutes of Health (NIH), but at Mizzou there’s the addition of Express to the program’s title. It stands for Exposure to Research for Science Students, which emphasizes the scientific aspect of the program.
Brian Booton, is the undergraduate director for MARC/IMSD-Express at Mizzou, acknowledges the prestige that goes along with being an MARC/IMSD scholar.
“It’s a highly selective grant,” Booton said. “There are only 49 programs in the country.”
With stiff competition for the program at universities across the nation, it’s important to focus on the students’ experiences.
“The ways in which IMSD-Express helps students is more than just research,” Booton said. “We try to expose students to the different pathways where further education can take them.”
Part of that is through the way the weekly meetings breakdown.
“I break programing down into three areas: personal, academic and professional development,” Booton said.
Doing so helps guide students in the right direction because it is set up to further their education by developing skills for success.
But it’s not all lectures and typical meetings. MARC/IMSD-Express offers a peer mentorship program for underclassmen apprentices to be paired with upperclassmen fellows.
“Even if you have a professor you really admire, there’s some distance there,” Booton said. “Someone that’s only two years older than you is more relatable; it’s spending time with your future self.”
The various research opportunities at Mizzou make it possible for students to supplement their classroom learning in a way unlike any other.
“It’s part of your education,” Blockus said. “Taking advantage of research is a great way to set yourself up for the future.”
For more information and to apply for these opportunities, visit:
