biochemistry

Paige Gruenke #IAmScience

Paige Gruenke

Paige Gruenke, a Ph.D candidate in Dr. Donald Burke’s lab in Bond LSC. | Photo by Mary Jane Rogers, Bond LSC

By Mary Jane Rogers | Bond LSC

“#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.”

Kwaku Tawiah #IAmScience

Kwaku Tawiah

Kwaku Tawiah, a Ph. D candidate in biochemistry at MU, stands near his lab station in the Burke Lab in Bond LSC. | photo by Mary Jane Rogers, Bond LSC

By Mary Jane Rogers | Bond LSC

“#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.”

Shannon King #IAmScience

Shannon King

Shannon King, a Ph.D candidate in the Biochemistry department at MU. She works in Scott Peck’s lab at Bond LSC. | Photo by Mary Jane Rogers, Bond LSC.

By Mary Jane Rogers | Bond LSC

“#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.”

Erica Majumder #IAmScience

Erica Majumder

Erica Majumder, a biochemistry Ph.D candidate. | photo by Morgan McOlash, 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.

Lloyd Sumner #IAmScience

Lloyd Sumner

Lloyd Sumner, biochemistry professor and Director of the Metabolomics Center at Bond LSC. | photo by Morgan McOlash, Bond LSC

By Mary Jane Rogers | Bond LSC

“#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

Scott Peck #IAmScience

Scott Peck

Scott Peck, a biochemistry professor at Bond LSC. | photo by Morgan McOlash, Bond LSC

By Mary Jane Rogers | Bond LSC

“#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.

Art of balance

Jinghong Chen | Bond Life Sciences Center

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Vinit Shanbhag mixes the CRISPR plasmid DNA with cells. The lab will test whether the gene of interest has been knocked out of the cells later. | photo by Jinghong Chen, Bond LSC

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.

Starving tumors

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Vinit Shanbhag mixes the CRISPR DNA with mammalian cells to specifically delete a gene in these cells in lab hood. | photo by Jinghong Chen, Bond LSC

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

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Michael Petris, a professor of biochemistry at MU, stands with his lab. From left to right: Vinit Shanbhag, Nikita Gudekar, Michael Petris, Kimberly Jasmer-McDonald, Aslam Khan. | photo by Jinghong Chen, Bond LSC

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.”

 

Michael Petris is a Bond LSC investigator and a professor of biochemistry. The study “Multiple di-leucines in the ATP7A copper transporter are required for retrograde trafficking to the trans-Golgi network” was published by The Royal Society of Chemistry in September 2016.

 

 

The Curious Case of Inflammation: One Lab’s Mission to Put the Pieces Together

White coat, dark room. Jean Camden, a senior technician in the Weisman lab, reviews salivary gland and brain tissue samples for research on inflammation. | Photo by Paige Blankenbuehler, Bond LSC

White coat, dark room. Jean Camden, a senior technician in the Weisman lab, reviews salivary gland and brain tissue samples for research on inflammation. | Photo by Paige Blankenbuehler, Bond LSC

By Paige Blankenbuehler | MU Bond Life Sciences Center

There’s a criminal on the loose, striking every day. Millions fall victim, but there’s still no way to stop it. And, in all likelihood, you have been hurt by it.

If inflammation is an unsolved criminal case of the last three decades, then Gary Weisman has been the detective. He’s certain there’s an accomplice — perhaps many — that may be triggering the discomfort.

The Bond Life Sciences Center investigator is slowly revealing what makes inflammation tick and what makes it strike. Each epiphany brings another question. He’s certain there’s a way to prevent negative effects of unsolved inflammation.

Bond LSC investigator and MU professor of biochemistry, has been studying the ins-and-outs of inflammation for the last 30 years. | Photo by Paige Blankenbuehler, Bond LSC

Bond LSC investigator and MU professor of biochemistry, has been studying the ins-and-outs of inflammation for the last 30 years. | Photo by Paige Blankenbuehler, Bond LSC

Weisman has dedicated his career to understanding the micro-processes behind inflammation. He’s become so specialized that his techniques can be as hard to crack as the case itself.

“I would not ask anyone to explain what I do,” Weisman says. Nonetheless, he’s been able to divide the process of inflammation into two categories: components that repair the body and components that lead to its destruction. This will help find inflammation’s many accomplices to figure out why humans work, and what their bodies do when they don’t work so well.

“I am interested in the meaning of life,” Weisman says. “Life has become simpler for me because the scientific method carries everywhere. I’ve become aware of how simple we are as a machine.”

 

Criminal or just misunderstood?

Most criminals adopt patterns, but inflammation stands as a signpost for mysterious, underlying problems.

Its effects are usually localized: an arm, a joint, the brain or a gland. You feel a temperature spike then the skin reddens in a part of your body. Later still, the skin tightens and pain comes at a snail’s pace.

Not even cells are safe. Inflammation even strikes on the molecular level.

But really, inflammation can be a good thing. It’s part of the immune system’s bag of tricks to signal the body to bring in reinforcements to fight off the invasion. Normally, inflammation corrects a physical problem, but if it is not successful in repairing a problem, inflammation can become chronic and accelerate tissue destruction.

Just like in an episode of CSI, Weisman puts the pieces of the inflammation puzzle together in his office by applying the expertise of Laurie Erb, Jean Camden and Lucas Woods — all donned in white lab coats, eyes pressed to the microscope examining evidence and building molecular evidence in the case.

The MU associate professor of biochemistry and his team have become a sort of grant-wielding wizards to sustain his pursuit of inflammation triggers. National Institutes of Health grant awards have sustained his lab for decades. The funding has come from varied sources such as the MU Food for the 21st Century Program, the Bond LSC, the Bright Focus Foundation, the American Heart Association and the Cystic Fibrosis Foundation. In recent years, research funding for Alzheimer’s disease and Sjogren’s syndrome (a disease of the salivary gland that causes dryness) have contributed, too.

But the funding source doesn’t matter because inflammation is the tie that binds.

Jean Camden processes samples under the Weisman lab's microscope. | Photo by Paige Blankenbuehler, Bond LSC

Jean Camden processes samples under the Weisman lab’s microscope. | Photo by Paige Blankenbuehler, Bond LSC

Advancements, like recent mapping of the human genome, have moved his work forward to understand inflammation’s complexity. Each experiment he completes fills in another blank slate in the “human owner’s manual.”

“As humans, we’re so intent on the fact that we’re superior to all, but really we’re not,” Weisman says. “With the Human Genome project, we’ve come to understand that all living things have similar designs … we are on the verge of finding revolutionary solutions to preventing or reversing human diseases.”

 

A receptor all our own

One specific player in the body’s immune system has kept Weisman’s attention for most of his career. The P2Y2 protein is a nucleotide receptor, and his lab team members affectionately refer to it as “our receptor.”

Nucleotide receptors are regulatory molecules in red blood cells. What they regulate is nuanced, mostly undetermined and of great interest to scientists. Answering that question has become Weisman’s wheelhouse.

The body manufactures 15 different types of nucleotide receptors, all similar in construction, but each are believed to have subtly different functional roles. It’s as if Weisman and his lab is on the case of a highly organized crime ring.

“Our receptor is mainly present when inflammation occurs, and we’re trying to figure out its role in a variety of diseases,” Weisman says.

The P2Y2 receptor has been observed in Alzheimer’s patients, along with a plaque build-up in the brain, and the receptor was suspected of playing a role in the disease’s progression.

Weisman and his colleagues found that the deletion of the P2Y2 receptor in a mouse model of Alzheimer’s disease accelerates progression of plaque build-up, neurological symptoms and death. This suggests that the receptor has anti-inflammatory effects rather than being “guilty by association” with the tissue-destructive aspects of inflammation.

“It’s like I have this 30,000-piece jigsaw puzzle in front of me that I have to put together,” Weisman says. “What’s the difference between you and me? As a machine, surprisingly very little.”

This simplicity drives Weisman to continue solving the mysteries of inflammation and search for its underlying chemical processes. By understanding the body’s chemical reactions, he believes treatments can be developed to focus the immune system on repairing damaged tissues.

Through studying his receptor, Weisman is breaking up inflammation’s crime ring.