Setting a routine makes everything easier. However, changes to a set routine often leads to complications.
For Maddie Willis, a senior biochemistry major, that change came in the form of working in different labs and learning their unique styles and areas of emphasis. She started in Lori Eggert’s lab freshman year and switched into Frank Schmidt’s lab for the next two years before changing labs a final time for her last year at Mizzou.
“I got involved in research as a freshman [in Eggert’s lab] through the Honors College Discovery Fellows program,” Willis said. “Then when Professor Schmidt retired, he recommended I look into Donald Burke’s lab.”
In Burke’s lab, she works with ribonucleic acid (RNA) aptamers — artificial RNA molecules that bind a particular target. Aptamers can be used for synthetic biology applications, molecular therapies and to investigate origin of life questions.
Willis works on the latter of the three questions and is characterizing features of an RNA aptamer that can discriminate between the two redox states of Flavin adenine dinucleotide (FAD) — a nucleotide cofactor that appears along with many others in modern metabolism. It has been hypothesized that they are holdovers from an RNA world, when RNA catalyzed prebiotic reactions before being replaced by protein enzymes.
“It’s unprecedented that we found an aptamer that can do that, because it’s such a minor change to the molecule,” Willis said. “I’m doing a reselection, allowing mutations to find out what still binds FAD, to find what’s important.”
Willis’ work is more in touch with human nature than anything else. If the aptamer can change the redox potential of bound FAD, it could potentially enable redox chemistry, which is essential for life.
“To an extent, we’re never going to be able to answer what actually happened at a molecular level billions of years ago,” Willis said. “My project, however, helps humanity to learn about where we came from.”
While the project doesn’t have immediate applications, its implications are significant.
“There are huge advances that come from basic research that no one could’ve anticipated, so it’s important to do,” Willis said.
After she graduates in May, Willis is looking to work in industry for a few years before attending graduate school.
“I had an internship last year, and I learned a lot,” Willis said. “I want to get real-world experience before pursuing more education.”
When she’s not in the lab working with RNA, Willis serves as an undergraduate research ambassador for the university.
“We support the office of undergraduate research by talking to students about research opportunities throughout campus,” Willis said.
It’s no secret that Willis has benefited from her time in the lab, so it makes sense she jumped at the opportunity to help others find their place too. In fact, it’s something that has rounded out her college career.
“Research has been the cornerstone of my experience at Mizzou,” Willis said. “Helping people find that is rewarding.”
“#IAmScience because research has really shaped the way I think about things.”
Science isn’t limited to the lab. It’s more of a mindset than a discipline, and Madeline McFarland knows this all too well.
As a senior biochemistry major working in Donald Burke’s lab in Bond LSC, McFarland experiments with ribonucleic acid (RNA) to study the origin of life before DNA and protein served as genetic material and catalyst, respectively.
“I’m interested in the RNA World Hypothesis and how RNA may have played a role in getting life started on our planet,” McFarland said.
This hypothesis suggests early forms of life on Earth may have relied solely on RNA to store genetic information and to catalalyze, or spur, chemical reactions. The theory goes that DNA eventually evolved to take its place due to the instability and ineffectiveness of RNA.
In the lab, McFarland focuses on using a program called systematic evolution of ligands by exponential enrichment (SELEX), which filters the RNA so she can find which strands do what she’s looking for. Specifically, she’s trying to determine if the RNA can make a reaction happen. If McFarland can find this connection, scientists would see that as support for for the RNA World Hypothesis.
“I’m trying to see which RNAs can perform a catalytic function,” McFarland said. “By doing that, we can kind of start to think about how RNA used to function in early earth.”
Her typical day starts at 9 a.m. when she heads to Bond LSC to get her experiments set up for the day.
“I go to class while they’re incubating,” McFarland said. “My science allows me to set stuff up and have a break while it’s running. I’m usually running experiments four days a week.”
McFarland was inspired by the work being done in Bond LSC and the analytical way of thinking about experiments.
“[Research] is kind of nailed into you as soon as you step on campus,” McFarland said. “That was the motivating factor, but I came to love it for a lot of reasons. It’s really shaped the way I think about things.”
When she’s not wearing her lab coat and investigating the origins of life, McFarland spends her time working in environmental efforts at Mizzou.
“I’m really passionate about sustainability in all of its forms: environmental, economic and social,” McFarland said. “I lead the electronic waste drives around campus, and I’m co-directing sustainability week this year.”
McFarland is also a co-president of the biochemistry club.
“In our meetings, we bring in grad students and faculty to talk about career options, so everyone can ask questions,” McFarland said. “We also do fun events. Last night, we had a biochemistry-themed breakout room. They had to balance chemical equations and transcribe and translate a DNA sequence to spell out a word. We have a lot of fun with it.”
All of her work in the lab in combination with her research at Bond LSC has only strengthened her bid for her next endeavor: medical school.
“I’m passionate about communicating science, and I think medicine would allow me to do that,” McFarland said. “I like the idea of radiology because it allows you to look at an image, or data, then think through things on your own, which is a lot like research.”
If she doesn’t end up at medical school, McFarland would like to continue to pursue education. She could see herself attending graduate school.
“I’m interested in a master’s in public health,” McFarland said. “It would allow me to expand my knowledge of science and how it relates to health beyond the scope of the lab.”
Regardless of if she continues to learn through medical or graduate school, though, McFarland credits research for having an immense impact on her career.
“Research has really shaped the way I think about things,” McFarland said.
“#IAmScience because I really enjoy discovering and being around people who cultivate a positive learning environment.”
As a freshman at Mizzou four years ago, Julia Brose knew she had a love for plants. That, however, competed with her fascination with biochemistry.
Luckily, she found and was selected for FRIPS, Freshman Research in Plant Sciences, which allowed her to do both. The program is made up of 10 freshman each year who gain valuable hands-on research experience with plants.
“I started working in Bond LSC, and that’s really where I found my love for research,” Brose said. “Working with plants allowed me to explore that interest, while still majoring in biochemistry. I have the best of both worlds.”
Her degree in biochemistry coupled with her research experience has given her a number of unique opportunities. One of which was being a Cherng Summer Scholar at Bond LSC last summer where she studied plants and their protein makeup.
“I was looking at amino acids, which are the building blocks of proteins in plants,” Brose said. “Specifically, I was looking for the content in seeds within Brassica, a species that includes cauliflower and kale.”
Another unique opportunity Brose earned was in summer of 2016. She worked at Stanford University as part of a fellowship for the American Society of Plant Biologists.
“I studied novel plant defense compounds —how plants protect themselves,” Brose said. “People can move around and gain protection that way, but plants need different chemicals to protect themselves.”
Her background in biochemistry and her experience with plant research at Bond LSC in Chris Pires’ lab provided her with the ability to analyze the defense structures in a unique way. As a result, she uncovered something that others had either ignored or overlooked.
“I found that the chemicals we see in leaves are in roots, too,” Brose said. “No one else had looked there before, so it was cool to be the first.”
Her work at Stanford led them to send her to a conference in Hawaii earlier this year. While there, Brose was able to present a poster on her findings as well as network with a number of successful scientists in a variety of fields.
As she nears graduation this spring, Brose has begun looking into graduate school options. Those are largely based upon the experience she had in Hawaii.
“I was able to make connections that have influenced my plans for the future as far as where I’m applying to graduate school,” Brose said.
Wherever she ends up, Brose hopes to teach.
“I like mentoring students and being around a learning environment,” Brose said. “That is really fostered in a university.”
“#IAmScience because I am fascinated by life on a molecular level and inspired that my research could positively impact medicine.”
As a graduate student in Donald Burke’s lab at Bond LSC, Paige Gruenke explores the role of ribonucleic acid, or RNA. That means her work involves a lot of test tubes. She looks at how specialized RNA molecules, called aptamers, bind tightly and specifically to proteins from HIV to prevent the virus from replicating. Her job is to locate the aptamers that bind to HIV proteins from a very large starting pool of RNA sequences by doing repeated cycles of removing the sequences that don’t bind and keeping the ones that do, until the strong binders dominate the population.
“A lot of the things I do don’t sound very exciting,” said Gruenke. “It’s throwing components into tubes and waiting for things to happen. It might sound mundane, but it’s all for the greater good.”
Gruenke hopes that her research will give scientists a better understanding of HIV, because understanding the virus will lead to better drug treatments and eventually, a cure. She is finishing up her second year as a Ph.D candidate in biochemistry, and plans to graduate by summer 2020. Gruenke has always been interested in the area of molecular medicine, but she has some advice for students who are just getting started.
“On a day to day basis, many experiments fail,” said Gruenke. “You’re always going to be learning something you didn’t know before. So, don’t be disheartened because something didn’t work out — just keep trying. Because whenever you have an ‘Aha!’ moment, it makes it all worthwhile.”
“#IAmScience because of where I come from. If you look at Africa, we have some of the most dangerous infectious diseases in the world…When you see these diseases first-hand and the havoc they cause, you want to solve the problem. People with different perspectives will make a difference in medicine.”
Growing up in Ghana gave Kwaku Tawiah a different outlook on medicine. Tawiah works in Donald Burke’s lab in the Bond LSC, and spends much of his time engineering nucleic acids and analyzing cell cultures. He hopes his research will help with early diagnosis of diseases, and wants to eventually bring it back to Ghana. He has a strong relationship with the other researchers and scientists in the Burke lab.
“In Bond LSC, and especially in my lab, it’s the people that matter,” said Tawiah. “When I came here, I knew nothing. I started with the basics and the people in my lab were patient enough to teach me the tools and skills that I needed. The people here are what keep me going.”
Tawiah said that his parents had a direct influence on both his education and career choices. Both his parents were teachers, so they were able to see his strengths and weaknesses, and saw that he was well suited for science. He completed his undergraduate degree at Lindenwood University in 2012 and is currently in his third year as a Ph.D candidate in biochemistry at MU.
For young scientists just starting off, Tawiah believes that you must be willing to learn and listen to the people around you.
“It doesn’t matter what you know, because if you’re humble you will do all right,” said Tawiah. “It’s not about what you know, but what you’re capable of knowing. If you’re not willing to learn, it’s going to be hard. Having a harmonious relationship with the people around you is key to learning.”
“#IAmScience because I plan to use my career to help develop agricultural innovations for the hard-working farmer.”
Most of Shannon King’s support system – her friends, grandparents, and boyfriend – are all farmers. They’re her inspiration and part of the reason her career goal is to use science to help farmers.
She’s currently a Ph.D candidate in the Biochemistry department at MU and works in Scott Peck’s lab at Bond Life Sciences Center. She’s also part of a $4.2 million grant the MU Interdisciplinary Plant Group received to fund crop research.
“I went into science because I wanted to help farmers,” King said. “With this grant, I get to go out into the field every day and be a ‘fake farmer,’ as I call it. And then I get to go into the lab and look at the science of it all. This grant gives me an everyday reminder of whom I get to help with my research and a whole new appreciation for science.”
The official name of the project is “Physiological Genomics of Maize Nodal Root Growth under Drought.” Its goal is to develop drought-tolerant corn varieties that make efficient use of available water. The project is interdisciplinary in nature and includes individuals from MU’s College of Arts and Science, School of Medicine, College of Agriculture, Food and Natural Resources, and School of Journalism. King said part of the fun of this grant is working with her team when things go wrong.
“None of us are engineers, but we’ve been doing a lot of re-engineering of our system to make things run smoothly. It’s rewarding to have all of us come together and try and make this project work.”
“#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.
“#IAmScience because I have an infinite curiosity and we have some powerful toolsets that I am confident will make a difference, not just in plant biochemistry, but in many scientific arenas.”
What change you would like to see in this world because of your research?
“I’m a technology junkie at heart. We are developing tools that can potentially advance many areas, and not just my own personal research program. I want to continue to build upon these tools and also apply them in a meaningful manner. On the plant side, I want to discover and characterize many new biochemical pathways, and use this information to make stronger, healthier and more productive plants. I also want to apply these cutting-edge tools to an ever expanding set of problems; i.e. cancer, veterinary medicine, nutrition, etc. I’m confident that every day when I get up, by the end of that day, week or month that we are making that difference.” -Lloyd Sumner
“#IAmScience because I want to discover. I want to ‘see’ – by understanding – things that others haven’t ‘seen’ before.”
Every day we make decisions based off on what we encounter in the environment. Plants do the same thing. Scott Peck, a Chicago-area native, is a biochemist who studies how plants translate information they receive about the environment (such as changes in light and temperature) into their own chemical “decisions”, also known as signal transduction. For him, it’s about making biology into a puzzle. Put the right pieces together, and you find ways to create more resistant crops or more effective antibiotics. With today’s technology and Peck’s passion for plant communication, anything could be possible.
It might be strange to say, but in a way the Australian soil led scientist Michael Petris to where he is now.
In certain areas of Australia, soils suffer from extremely low level of copper bioavailability, resulting in poor growth and neurological problems on sheep.
Petris, a Bond LSC investigator and professor of biochemistry who was born in Australia, now spends his time studying how copper, an essential mineral in human body, works in cells to build and maintain essential functions.
Recently published work from his lab focuses on how the ATP7A protein, one of the major proteins, cycles within the cell.
“Copper is solely acquired from diet. The absorption of copper from the intestine in the blood needs ATP7A,” Vinit Shanbhag, a Ph.D. biochemistry student at Petris’ lab and an author of the study, said. “It transports copper to different copper dependent enzymes and exports free copper from the cell to the outside.”
After exporting copper at the cell membrane, ATP7A needs to come back to its steady-state location within the Golgi apparatus of cells – via a process called retrograde trafficking. But one question baffled scientists: what are the key elements that lead ATP7A coming back?
Back in the late 90s, Petris discovered the importance of one single di-leucine in retrograde trafficking of ATP7A. For those of you wondering, leucine is an amino acid that forms the building blocks of proteins like ATP7A, while di-leucine consists of two of them connected via a peptide bond.
His team wished to identify other signals for retrograde trafficking, but one technical hurdle stood in the way— the ATP7A gene is unstable when grown in bacterial plasmids, the traditional way of amplifying genes in the lab.
Commercial DNA synthesis was the answer. This method could create artificial genes in the laboratory.
“We reasoned that if we introduced enough silent mutations into a DNA sequence, we could avoid or change the region of instability in the native sequence without affecting the encoded protein,” Petris said.
To stabilize the gene, they changed more than 1,000 nucleotides within a 3,000 nucleotides segment, and thus solving the problem of instability of the ATP7A gene. In doing so, they subsequently found that in fact multiple di-leucines that are required for retrograde trafficking of ATP7A. This approach could be used by other laboratories whose gene of interest is also unstable.
An overlooked mineral
“If you ask [people], is it important to understand iron nutrition? Is it important to understand calcium nutrition? Most people would say of course! … But, perhaps you would not get the same answer for copper, despite the fact there is a little dispute that copper is important,” Petris said.
As an essential micronutrient, copper performs central functions to develop and maintain human skin, bones, brains and other organs.
“If you don’t have enough copper in your body, you cannot use oxygen to make energy,” Petris said. “If you don’t have copper, you would not survive.”
Pregnant women who carry a mutated ATP7A gene on their X chromosome can pass it on to their children in the form of Menkes disease.
Menkes disease is a genetic disorder that results in poor uptake and distribution of copper to cells. The incidence of this disease is estimated to be one in 100,000 newborns, according to U.S. National Library of Medicine.
Infants with Menkes disease typically begin to develop symptoms during infancy and rarely live past the first few years of life. Abnormally high accumulation of copper in kidneys and low-level accumulation in the liver and brain, cause visible symptoms like sparse hair, loose skin and failure to grow.
Despite copper’s importance, it also can be a potentially toxic nutrient.
“Copper deficiency can be a problem but too much copper is also a problem. There should be a balance,” Shanbhag explained.
The liver normally stores excessive copper and excretes it into bile to release it out of the body. Yet people with genetic disorders that preventing copper excretion might suffer Wilson’s disease, leading to life-threatening organ damage.
Shanbhag said people with Wilson’s disease accumulate toxic amounts of copper in liver and other organs, causing Kayser–Fleischer rings that encircle the pigmented regions of the eye, a hue caused by copper deposits in the cornea.
Its clinical consequences differ from chornic liver failure to neurological sysmptoms like tremors, dystonia, ataxia and cognitive deteriortation.
About one in 30,000 people have Wilson disease, according to National Institute of Diabetes and Digestive and Kidney Diseases.
In 2013, Petris’ lab published the first direct evidence suggesting ATP7A is essential for the dietary absorption of copper. Since then they have dug deeper into this copper transporter, and his lab now sets their sights on a greater enemy of human health — cancer.
Tumor growth requires access to large amounts of nutrients. Without an adequate supply of oxygen and nutrients, tumors fail to grow and survive. Scientists have identified that by preventing access to nutrients—for example by blocking the growth of new blood vessels—they could starve the tumor of nutrients.
Copper is a key nutrient for tumor growth. With the new-introduced system CRISPR-Cas9 — a genome editing tool to knock out specfic genes — his lab has explored how to exploit understanding of copper metabolic pathways to withhold copper from cancer cells.
“Copper starvation might be a good approach as an anti-cancer strategy,” Petris said.
Weapon of the immune system
Currently, four members study in Petris’ lab to tackle the relationship between copper and various diseases. Petris plans to expand his research to another area: the role of copper in innate immunity against bacterial pathogens.
This is the topic of Petris’ next grant. Nutritional immunity, which describes how the mammalian host withholds nutrients from the invading bacteria during infection, is very well-described for iron and zinc.
Yet copper performs differently.
During infection, the level of copper in blood actually goes up instead of going down. The immune system concentrates copper at sites of infection and within regions where the bacteria are engulfed.
“We speculate that copper is being used as weapon by the host to kill the bacteria,” Petris said. “That is the area we are trying to develop further.”