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A closer look at MU research: Discovery science at the cellular level

Posted on 26 April 2011 by Melanie Pawlyszyn

Marquette professors honored for their research

Four Marquette University professors were recognized for their ongoing research on Monday, March 7 at the annual Distinguished Scholars Reception. Dr. Rosemary Stuart, a professor of biological sciences received the Lawrence G. Haggerty Award for Research Excellence. Dr. SuJean Choi, an assistant professor of biomedical sciences, and Dr. Martin St. Maurice, an assistant professor of biological sciences, both received the Young Scholar Award. Dr. Sebastian Luft, an associate professor of philosophy received the Way Klingler Fellowship Award.

Dr. Rosemary Stuart

Yeast. When you hear this word, what first comes to mind? Beer? Brewing? Fermentation?

Yes, yeast can carry out fermentation, the process used in making alcohol, but it can also be used in biological research at the cellular level.

Rosemary Stuart, Ph.D., a professor of biological sciences, has been using yeast cells in her lab in the Wehr Life Sciences building with graduate and undergraduate students since she came to Marquette in 1999.

With her soft Irish accent, Stuart began explaining and simplifying science that could take a lifetime to understand: “We are made of hundreds of thousands of millions of cells…”

Each of these cells has a mitochondria, its powerhouse, that makes energy, also known as ATP. The process in which energy is created in the mitochondria is called oxidative phosphorylation. This process requires a number of enzymes to work together in a specific way.

“An enzyme is a protein molecule in the cell,” Stuart said. “Basically it’s a catalyst – acts to speed up a reaction, how fast a reaction can go from start to finish.”

Stuart’s lab studies how enzymes are assembled in the mitochondria, how they function and are regulated, and how they work with proteins to create ATP.

“There are many diseases that exist that are known to have their primary defect in mitochondrial function,” she said. “And, so, if the energy production is not optimal, then the muscles, for example, won’t be getting enough ATP. So there’re many neuromuscular diseases that are about, cardiac diseases that have primary defects in the mitochondria, many different diseases.”

One of the proteins Stuart looks at is called the ADP-ATP transporter. This protein is involved with a disease called ADPEO, which affects eye muscles. A defect in ATP production causes muscle dysfunction that leads to droopy eyelids and eyeballs that cannot move left and right.

“Many patients that have this disease will have a primary defect in this transporter protein,” Stuart said.

In this case, and in with all her research, Stuart uses yeast cells to replicate the cell’s mutation as a model for the disease.

“We can look at mitochondrial mutants, so in other words, cells that are defective in ATP production in yeast, because they’re still viable,” Stuart said.

Dr. SuJean Choi

According to the Centers for Disease Control and Prevention, a 2007-2008 survey showed an estimated 34.2 percent of U.S. adults aged 20 years and over are overweight (BMI 25-29.9), 33.8 percent are obese (BMI > or = 30) and 5.7 percent are extremely obese (BMI > OR = 40).

Evolutionarily, fat stores in the body were important energy sources for survival. When people confronted famine, periods of fasting or could not get to the mastodon right away, they could always turn to their fat stores to get calories in a small amount of time and space.

Unfortunately, our instincts to eat foods with high amounts of fat, sugar and calories have stuck with us over the centuries. In a culture where food is inexpensive, calorically dense and easily accessible, obesity has become a huge problem and can lead to many negative consequences. These include hypertension, risk of heart attack, stroke, atherosclerosis (clogging of the arteries) and most importantly, type II diabetes, where the body cannot regulate its own blood sugar.

Why do we eat so much? How does the brain tell us when to eat and when not to eat? What allows the brain to supersede signals that tell us to stop?

These are questions that SuJean Choi, Ph.D., an assistant professor of biomedical sciences, has been trying to answer since she was a postdoctoral fellow at the University of California – San Francisco twelve to thirteen years ago. She joined the faculty at Marquette in October of 2007 and now works with two technicians, a graduate student, a postdoctoral fellow and six undergraduate students in her lab in the Schroeder Complex.

Choi said: “The goal that I have for my research is I hope it contributes down the road to two things: understanding how the brain works, just adding to the basic knowledge that we have, and two, enabling others to sort of design better approaches, design better means and drugs to address issues like eating disorders and obesity.”

Research Projects

Choi’s lab is working on two main projects. The first looks at commonly used appetite suppressants called SSRIs, or Serotonin Specific Reuptake Inhibitors. These drugs improve and increase the amount of serotonin in the brain, a neurotransmitter that causes a decrease in appetite.

SSRIs curb people’s appetites at first, but they start to lose their effects after three to six months, Choi said. This is obviously a problem because it takes an obese person more than three to six months to lose significant amounts of weight.

Choi said she sees this happening to rats in her lab at a much quicker rate. After injecting little shots of the SSRI into rats’ brains, the rats do not want to eat anything. About five days later, the drug becomes ineffective and the rats look just like the control rats that were not drugged.

Her lab observes which genes are expressed and not expressed during this whole process. Choi is working to understand the brain signals that lead to eating disorders, obesity or other metabolic disorders that keep energy off balance. Finding these answers could help scientists design effective weight loss treatments.

“We’re trying to understand how the brain receives information from the body,” Choi said. “How does it know how much fat, how much protein you have in your muscles and your fat stores? How does it know what’s out there? And what does it do when it gets those signals, and how does it curb your appetite?”

The second project in Choi’s lab looks at PACAP, a protein that plays a role in feeding. Scientists do not yet know what that role is. The protein is located in the feeding area of the hypothalamus, a little region in the brain that controls housekeeping functions, like feeding drive, sex drive, thirst, sleep and wake cycles and heat regulation.

“We started giving animals PACAP, and we find that when we give it to them, they shed a lot of weight,” Choi said. “They stop eating right away, and their temperature goes up, so they’re burning a lot of calories. And they tend to be very active, so they’re showing locomotive behavior. We can measure all these things.”

Dr. Martin St. Maurice

Martin St. Maurice, Ph.D., an assistant professor of biological sciences in the Wehr Life Sciences building, studies how proteins function to carry out chemical reactions that are essential for our survival.

He has been working on this research since he came to Marquette in September of 2008. St. Maurice currently works with two graduate students, one Ph.D. research scientist and four undergraduate students in the lab. He worked on similar research as a postdoctoral fellow at UW-Madison one to two years prior to coming to Marquette.

Research Projects

Imagine a car assembly line, where parts are systematically assembled to create functional vehicles. If DNA is like a car’s blueprint, the car is a protein. DNA is the hereditary information of life that gives proteins instructions for all chemical reactions in the body. When all the parts of the car are assembled properly, the car can go out on the road to drive. And like cars, proteins come in all shapes and sizes, ranging from smart cars to hummers.

“Simply from the way there’re folded up, there is an inherent, very specific function to them,” said St. Maurice. “Every protein, based on the way it is encoded, the instructions for its synthesis, is different and unique in the way that it’s folded, in the way that its molecules are oriented to catalyze a particular reaction or to carry out a specific task.”

In order to find out how proteins work together to carry out those tasks, structural biologists like St. Maurice must make pictures of the proteins.

A reel of film runs at about 24 frames per second. That means that a 2-hour movie has about 200,000 frames. You cannot possibly understand the story from any one single frame that shows only a snippet of action from the whole.

This is how pictures of proteins in the lab work too. And the more structurally complicated the protein, the more frames that are needed to tell the story. The question is, ‘How many pictures does it take to tell it? Dozens? Hundreds? Thousands?’

“Most of the time, these proteins are black boxes,” St. Maurice said. “We have no idea how they are structured. And since we have no idea how they’re structured, we have a difficult time understanding the intricacies of how they work. So the minute you get a photo of something, you all of a sudden have vastly improved insights into how something works.”

St. Maurice uses a technique called X-ray crystallography to take pictures of proteins. In this process, he grows protein crystals and uses a machine called an X-ray diffractometer to shoot X-ray beams at them. From there, he works to find the structure of the proteins. The entire process takes over a year if things go well, he said.

One of the proteins that St. Maurice is looking at has a critical role in the release of insulin in the pancreas in response to elevated glucose levels. So it keeps blood sugar levels from getting too high. This same protein is also important for making glucose in the liver and kidneys when blood sugar is too low.

Understanding the structural information in the protein can help show how this process works, though it is difficult to pinpoint change, St. Maurice said.

St. Maurice said: “One of applied goals of research is to try to understand to hope to someday to be able to manipulate the system a little bit. Maybe this enzyme is a reasonable target for people who are suffering from type II diabetes.” Scientists have not looked at this protein too much in the past, he said.

Working in a Lab – Struggles and Strides

Research discoveries involve a combination of hard work, intelligence, skill and even a little bit of luck. Scientists are constantly building a body of knowledge, interpreting results and asking more and more questions along the way. They need much patience to tackle questions that develop over a lifetime.

Stuart said lab work can get frustrating at times. “You’re opening one door and then you find out there’s many more there. So you’re answering one question, but through the course of answering that question, you’ve actually opened up some more questions that you then go on and pursue,” she said.

Choi said: “The hardest part in the lab is just keeping that in mind that, you know, for every ten failures, we get one success, and that’s how all the science labs work. It’s just always a little saddening when you come across that, but you gotta kind of keep marching on. Eventually, you have some really cool result, and it just makes your day.”

Collecting new information and asking questions is how discovery science evolves. In fact, Stuart said the reason she ended up studying certain enzymes came by surprise.

“We hadn’t planned on studying it,” said Stuart, “but we had one or two observations that kind of drew us in that direction and the pieces of the puzzle all fit together. And it’s like ‘Ah!’ you have that eureka moment, ‘This must be what’s going on!’”

St. Maurice said the thrill of discovery motivates him and drives his research forward.

“I think it’s true that in research 90 percent of the time things fail,” he said. “It sort of feels a little bit like you’re constantly beating your head against the wall. And it hurts after a while, right? But it’s worth it for that five to 10 percent of the time when something does work and suddenly you’re seeing something that nobody else has ever seen before.”

Teacher-Scholar Model

Unique from other university professors, all Marquette professors of biological sciences follow a teacher-scholar model that allows them to conduct research along with teaching undergraduate and graduate classes. This is what attracted Choi, Stuart and St. Maurice to this university.

Professors encourage as many undergraduate students as possible to get involved with their labs and do independent research, Stuart said. St. Maurice pointed out that at least one undergraduate student works in each lab on campus.

“You can learn so much from a textbook,” said Stuart, “but actually coming in as a biology major and working in somebody’s lab and generating data, analyzing the data and discovering something new teaches you so much that you’re not going to get from a textbook… We have the best of both worlds.”

Equally or even more rewarding than the feeling of discovery, said Choi, Stuart and St. Maurice, is seeing the same kind of excitement in the students working in their labs.

“It’s unparallel, the excitement feel that you get when something works for the first time,” said Stuart, “but also just the fun you have of mentoring and working together alongside young people and mentoring them and guiding them and seeing them have fun discovering is wonderful.”

Choi said: “One of my favorite kinds of experiences is that when I see that in my students, when they get excited and see that all that hard work and all those little failures that we went through, that, all of a sudden, they’re kind of jumping up and down, and saying, ‘That’s really cool.’”

Helping students become independent in their research is rewarding, St. Maurice said. “To feel like you’ve been able to have some small part in their experience and their adventures is pretty awesome,” he said. “It’s a great part of the job.”

St. Maurice said: “I think Marquette both fosters and attracts teacher scholars who… are interested in their scholarship and it’s what brought them to this point in their careers, but they’re also very interested in sharing that with students. To be able to share that thrill is really important, I think, to a lot of people here.”

Bringing Science Home

Running laboratory research is an around-the-clock effort that constantly changes. As scientists find new information, many new questions arise. Scientists must keep their brains on overtime to keep up with the exciting, quick flow of new information, hypotheses, methodologies and interpretations. This includes keeping up with the findings of other scientific research to shed light on their own.

Research is a lifetime endeavor. So when do scientists find time to live normal, sociable lives?  How do they cope with constantly processing new information?

Choi said she likes to keep her science and home lives completely separate. The self-described “crazy Frisbee lady” plays ultimate Frisbee with the Milwaukee Ultimate Club city league.

“I usually try to get the Valley Fields during the summer,” said Choi, “and I try to organize a pick-up, so anybody can come and play down there during the summer, and so I get half my faculty department to come down there, and I get a lot of our students. And it’s almost a requirement to be in my lab that you have to play ultimate.”

Stuart said there are days when she goes home and constantly thinks about her lab work. She likes to read scientific literature especially when she is eager to find out what a result from the lab might mean. She said when she relaxes at home, for example: “I’m not really watching TV, although I’m thinking I’m watching TV.”

To release her mind from the constant wheels of scientific thought, Stuart likes to take walks, a lot of walks. She also enjoys photographing nature with her Canon 40D.

St. Maurice said having a job that is flexible and free has its advantages and disadvantages. “You don’t have to ever turn off,” he said. “You’re always thinking about what’s going on [and] worried about what’s not working.”

For fun, he plays the fiddle with a community orchestra once a week. He said, “It’s remarkable that while I’m in those rehearsals for three and a half hours, I don’t think for a second think about everything that’s going on in the lab.”

by Melanie Pawlyszyn
[email protected]

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