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At the Crossroads of Chemistry and Biology

by Alicia Gregory

Every living thing can be reduced to chemicals. Carbon, hydrogen, nitrogen—these chemical elements are the foundation for molecules that form the intricate, three-dimensional structures we know as DNA. Scientists at the University of Kentucky are focusing on the chemical roots of life in a new program designed to solve biological problems through chemistry.

Photo of Boyd HaleyBoyd Haley was one of the first scientists hired at the UK Markey Cancer Center and was a faculty member in the College of Pharmacy from 1985 to 1997.

While federal funds have dried up for traditional chemistry areas like weapons research, federal agencies and pharmaceutical firms are eager to fund biological chemistry, says Boyd Haley, chair of the chemistry department at UK. "The Cold War is over. We've lost federal funding to develop better war materials, so the focus of chemical researchers has switched to things like environmental toxins that affect biological systems, and sensors for medical diagnostics.

"What we're setting up right now is an undergraduate degree program—a degree in chemistry with an emphasis in biological chemistry," Haley says. "If you're a smart student, you'll realize that getting an undergraduate degree in biological chemistry will increase your chances of getting into and surviving medical, dental or veterinary school, because it just so happens that in those professional schools the major flunk-out course is biochemistry."

It's clear that this is a hot job market, Haley says. "Take a look at the number of want ads in the back of Science, the major magazine where companies advertise for research people. The majority of these jobs require biological chemistry expertise."

Before this program began in the chemistry department, the closest thing on the UK campus was a Ph.D. program in biochemistry through the College of Medicine. "The university needs all of these—undergraduate and graduate programs—to provide a top-notch education," Haley says. "In the Ph.D. program they zero in on medical applications, while we are doing a wide range of basic research. If you look at top 20 universities, they all have a biochemistry department and a chemistry department with a biological emphasis.

"Biological chemistry varies from biochemistry in that it usually involves application of 'heavy-duty' chemical techniques to biological problems such as using mass spectrometry and nuclear magnetic resonance," says Haley. He adds that an understanding of the various areas of chemistry, such as physical chemistry, and their application to biological problems is more heavily emphasized.

Biological chemistry was one of 11 strong research areas identified by UK as part of the Research Challenge Trust Fund (RCTF) initiative. Established by the 1997 Kentucky Postsecondary Education Act, one phase of RCTF includes $16 million to support new faculty, graduate students and staff in the selected areas.

The biological chemistry program received $3 million to renovate lab space and hire four research faculty and eight research assistants. The four new faculty, in addition to "five outstanding UK faculty" who have been conducting research in biological chemistry, are shaping a solid research and education enterprise, Haley says.

"Obviously, when you launch a new program, you hire new faculty to teach the courses," Haley says. In addition to teaching undergraduate courses in biological chemistry, each new faculty member will be responsible for developing one graduate-level course in his or her area of expertise.

Haley was one of the first scientists hired at the UK Markey Cancer Center and was a faculty member in the College of Pharmacy from 1985 to 1997. He joined the Department of Chemistry the following year as professor and chair. "I came to the chemistry department because I wanted to teach graduate students," Haley says. "The level of work I do requires people who know a lot of chemistry."

Haley says today's booming biological chemistry market is one result of the Bayh-Dole Act of 1980, which enabled small businesses and not-for-profit organizations to retain title to innovations made under federally funded research programs. As a result, there was an explosion in the number of start-up biotech companies. "All of a sudden I can invent something, have the university patent it, and I'm allowed to take it and convert the new intellectual property into a business that will make money, create jobs and serve the public," Haley says.

"A large number of jobs available today are with companies that started out very small and are now large and have actually overtaken the old-fashioned pharmaceutical firms," he says. "It doesn't take a lot of money to start one of these companies—you find a protein that causes a disease, make an antibody to it, develop a simple Western blot test, and start selling your technology to the world."

Haley himself has transformed a technology developed in his lab into a thriving biotech company named Affinity Labeling Technologies Inc. (ALT). He co-founded ALT in 1998 with Curt Pendergrass, who received his Ph.D. in toxicology from UK in 1995 and worked as a postdoctoral fellow in Haley's lab for nearly four years.

Located on the UK campus in the Advanced Science and Technology Commercialization Center, known as ASTeCC, ALT develops, manufactures and markets nucleotide photoaffinity probes—radioactive compounds used in research and diagnosis of disease. When these photoprobes are exposed to ultraviolet light, they bind to the active site of the protein, allowing it to be permanently tagged for identification. ALT uses photoprobes to diagnose periodontal disease and test toxicity levels before and after tooth extraction, and is selling this technology to a worldwide market.

And just recently, German scientists at the University of Göttingen confirmed findings that Haley published in 1992 in the proceedings of the National Academy of Sciences that proposed a diagnostic test for Alzheimer's disease. "UK owns a patent on this, and I hope to be able to make the test available as an aid for early Alzheimer's diagnosis," he says.

"In terms of cutting-edge research, I'd say chemists at UK are very close to the front of the pack in many areas, despite the fact that we just don't have the number of researchers other universities have," says Haley. "There isn't a better biosensor group in the country than the one here led by Leonidas Bachas and Sylvia Daunert. They have organized a major NSF graduate training grant in the biosensor area in addition to their personal grants, which are extensive. We have an excellent materials research center with Robert Haddon, and Allan Butterfield's research in protein oxidation in neurological disease is known around the world," Haley says.

"And add to these great strengths our new biological chemistry faculty. Tae Ji is absolutely the king of his area. Anne-Frances Miller is an outstanding protein NMR researcher—in the front of her field. Edward DeMoll's research is first-rate, and he is collaborating with outstanding researchers across the country. Stephen Testa is just beginning, but his ideas are outstanding.

"Our new faculty alone brought in over $1 million this year and a huge amount of free research equipment from their established laboratories. We're well on our way to paying back that $3 million investment in the program."

The chemistry of reproduction
Boyd Haley and Tae Ji (pronounced "Gee") are longtime friends. As colleagues at the University of Wyoming for almost a decade, they changed the face of biological chemistry. "Boyd and I were instrumental in drawing international attention to the biological chemistry center at Wyoming in the particular area of research called photoaffinity labeling," says Ji, who spent 30 years as a professor at Wyoming.

Photo of Tae JiBefore the UK offer, Tae Ji says he was concerned about reestablishing his reputation at another university, but because he already knew Haley, he could continue to focus on his research here.

"Scientists from all over the world came to that center, and we traveled all around the world giving lectures," says Ji, a native of Korea, who did his doctoral work at the University of California at San Diego. "Boyd and I have been very competitive over the years, but our relationship is built on mutual respect of our science. I was very sorry when he left the University of Wyoming."

Haley played a major role in getting him to come to Kentucky, says Ji. "I had been getting offers from other universities, but I didn't go."

So what convinced Ji to come to the Bluegrass? "I knew I could trust Boyd, but there's more to the story than friendship. Before the UK offer, I knew that if I moved to a new university, I'd have to reestablish my reputation, starting from ground zero. But at UK I didn't have to do that because the chair of the department knew me. I could continue to concentrate on my research—that was a major factor," says Ji. "Boyd's vision of creating a new group of scientists in the chemistry department emphasizing chemical approaches to biological problems struck me as an approach that would work very, very well."

Ji says the reason chemical approaches are so attractive today is the advent of molecular biology. "Chemical approaches were very popular and effective about 30 years ago, but in the meantime molecular biology rose to prominence. Now that the molecular biological approach has been fully utilized and chemical tools have become much more advanced, we are using chemical approaches on top of our molecular technology, and this combination has become a new, powerful method of solving biological problems," he says.

Ji was the last scientist of the four RCTF faculty Haley was trying to recruit, and Ji says that when Haley showed him the new faculty members' vitas he was very impressed. "I thought I could fit in with the rest and we could really create some powerful teams," he says. "The existing faculty have outstanding backgrounds in chemistry—in particular, analytical, inorganic, organic, physical and radio chemistry. Being able to tap into such expertise is an opportunity you don't get too often."

Ji's research focuses on three hormones, LH (luteinzing hormone), FSH (follicle stimulating hormone), and HCG (human chorionic gonadotropin). LH and FSH are involved in the development of gonads in both sexes and the control of sexual cycles in women. "These are the crucial hormones in regulating ovulation cycles," Ji says. "They have to come in at the right time, in the right sequence for ovulation. Obviously, these hormones are important for succession of the species, but in addition they are keys to solving infertility, making better contraceptives, and treating menopause."

Sixteen percent of families in the world face infertility, Ji says. "Infertility is a problem for both sexes. We know a lot less about problems with sperm production than we know about infertility in women, but the same hormones are at work," Ji says.

"The contraceptive pills that have been used for the last 40 years or so are steroid hormones, and those hormones go into every cell in the body and affect cell function regardless of what that cell controls. When the pill first came out about 50 years ago, the dose was 50 times higher than the current dose, and we saw tremendous side effects—cancers, gene disruption—and researchers said the maximum time period you could take the pill without major effects was five to 10 years," he says. "Future contraceptive pills will use non-steroid hormones that will target only the ovary and will eliminate side effects."

FSH also plays an important role in the acute phase of prostate cancer. "We recently, in collaboration with other groups, have found that prostate cancer cells start producing FSH and its receptor molecules simultaneously. We think the reason the cancer cells proliferate and the patient dies is because FSH stimulates cell growth and division," Ji says.

The third hormone, HCG, is key in protecting fertilized eggs. "When an egg is fertilized, the first thing it does is go to the mother's womb. As it starts developing, it produces HCG, which blocks the initiation of menstruation." Without HCG, the egg will be flushed from the womb when the woman menstruates and she will have a miscarriage. This hormone is critical in the first three months of fetal development, Ji says. "All pregnancy tests test for HCG."

This hormone may also hold the key to early diagnosis of some cases of ovarian cancer. "Most of the time when we find this cancer, it's too late," Ji says. "Some ovarian cancer cells produce HCG, and there is a group of scientists right now trying to find out why that occurs so that they can work to develop diagnostic tools to detect HCG in these cells."

HCG, LH and FSH have high specificity, which means they bind only to certain molecules called receptors. Once these hormones bind to the receptor, it generates a signal. "The focus of my research has been to learn how the hormone and receptor interact and how occupied receptors generate hormonal signals," says Ji. "If we can identify the precise mechanisms, we will be able to generate the hormonal signals without having the particular hormone present." So instead of taking hormonal pills, Ji says, you could spray something into your nose with a chemical that simulates a specific hormone to fool the receptor into generating the desired signal.

In addition to the array of medical applications in humans, Ji says his research may also impact animal breeding. "Veterinary science labs and biotech companies are using these hormones to regulate cycles in cattle, and that's a huge market. These hormones will impact horse breeding and in-vitro fertilization in all kinds of animals and in humans," says Ji. "For in-vitro fertilization you need lots of eggs and the way to make them is to use these hormones."

Changing the shape of chemistry
You could say Stephen Testa has gone "where no man has gone before" in the chemical world. Armed with a Ph.D. in biochemistry and molecular biology from Purdue in 1994, Testa went to the University of Rochester in New York to "start something new." A half year later he had generated enough preliminary data to apply for an NIH postdoctoral fellowship, which he was awarded.

Photo of Stephen TestaStephen Testa: "It's exciting to get in on the ground floor of something like this, especially as a junior faculty member."

"The essence of this new area is creating a better way to develop therapeutics from small portions of DNA," Testa says. "We know that certain regions of DNA are important for certain diseases, and we know we can target them by simply making DNA that will bind to these targets. The buzzword for the way this is currently done is 'antisense.'

"Antisense simply means you target the linear sequence of a gene. All genes are made up of adenine (A), thymine (T), guanine (G), and cytosine (C). Because we know that A pairs with T, and G pairs with C, we can easily design a complementary molecule that will bind tightly to the region we're targeting, shutting it off and potentially stopping the disease."

The problem is that these molecules are relatively long, resulting in non-specific binding to the DNA, Testa says. Essentially, this long strand sticks to other regions in the DNA that have a sequence similar to the target site. "So the idea that Doug Turner—my postdoctoral advisor at Rochester—and I came up with was to find a way to make these molecules shorter. And the way we do that is to exploit the fact that RNA can fold into three-dimensional, biologically active structures. Up until now it has been widely appreciated that only proteins can be exploited for drug design in this manner," he says. "What we did was show that RNA does form these structures, and that you can target them with small molecules and potentially affect biological activity."

In addition to this method of creating DNA that fits like a puzzle piece into a specific spot on the RNA chain, Testa is working on an experimental tool to test potential therapeutics. This new and powerful "combinatorial method," as he calls it, will allow him to test billions of these small molecules simultaneously and single out the ones that work best.

"For example, if you want a therapeutic that is 16 bases long, there are billions of possible different sequences. If I were able to test even a thousand a day with current methods, it would take over 10,000 years to test them all. I'm developing a method where we can test all of them in about a week.

"There are certainly important advantages to using such technology for drug development, not just to save time but also to reduce cost. This technology will give us the ability to learn about disease targets we currently know nothing about," Testa says.

As scientists identify more and more genes responsible for disease, the opportunity to develop specific therapeutic molecules grows. "There's no better time than now to start thinking about how we can use biological chemistry principles to design therapeutics against specific diseases," he says.

"In the project where I'm developing the combinatorial method, the model target is a potentially lethal fungus that causes pneumonia in AIDS and cancer patients. I'm also working with DNA that causes a type of muscular dystrophy called myotonic dystrophy," he says. "We've known for nearly 10 years what happens to your DNA and RNA when you have this disease—certain regions grow longer, or expand. What I'm working on is a novel method to cut the expansion out, which will essentially fix the RNA and/or DNA. Because we know an essential step in this disease, there's absolutely no reason why we can't start developing therapeutics that will make a big difference in people's lives."

If he succeeds in cutting out that expansion, Testa says the method will be applicable to a wide range of diseases, including AIDS and cancer.

While the reasons why this expansion occurs are still a mystery, Testa says in the past year alone scientists have made breakthrough discoveries about why this expanded region causes the effects you see in myotonic dystrophy patients. "I'm certainly not the first person to think about developing a therapeutic for this," says Testa, "but very few scientists have tried to target this disease at its fundamental source.

"There's an important reason I'm in the chemistry department despite the fact that most of my training has been in biochemistry and biophysics. All biomolecules are simply chemicals. There are no magical properties at work here; these biomolecules follow all the rules we learn in basic chemistry, and it's precisely this kind of information that we want to exploit for designing new therapeutics.

"Here at UK there is a lot of opportunity to form interdisciplinary collaborations, not just within the chemistry department but throughout the entire campus. It's exciting to get in on the ground floor of something like this, especially as a junior faculty member."

An anaerobic way of life
Edward DeMoll was right under Boyd Haley's nose, but it took a phone call to NSF to find him. "Dr. DeMoll, who we got from the UK medical center, I found by talking to a program administrator at the National Science Foundation," says Haley. "I asked for leads on good, young faculty in biological chemistry that I might attract to UK, and he said, 'Well, you've got one right in your back yard. You should go after Eddie DeMoll.' So I met him at an American Society for Biochemistry and Molecular Biology conference in San Francisco. I just walked up to him during his poster presentation and introduced myself."

DeMoll now has dual appointments, a primary appointment as an associate professor in chemistry and another in microbiology and immunology in the College of Medicine. "In mixing disciplines you find you're doing research a lot of people don?t think about doing because you've got two different viewpoints on things," he says.

Photo of Edward DeMollTo do his research, Edward DeMoll uses "glove bags" because he has to work in the absence of air. "Before these tools were developed, we had to work in a room filled with nitrogen. We had to wear breathing equipment and work in pairs because of the danger. It was pretty eerie, because all you could hear was your own breathing."

Methanogens, organisms that produce methane gas, have been DeMoll's research focus since he was a postdoc. "All forms of life are either bacteria, archaea or eucharyotes," he says.

He explains that archaea are of three different types: methanogens, extreme halophiles (they live in very high-salt environments), and extreme thermophiles (they live at very high temperatures). Extreme thermophiles include organisms that live on the ocean floor near hot thermal vents and in the hot springs in Yellowstone National Park. DeMoll says there is some overlap between these three groups of archaea. "Some of the methanogens are also extreme thermophiles. I work with one that we grow at 75 degrees Celsius. Also, extreme thermophiles and methanogens are all anaerobic (they live in the absence of oxygen)."

Scientists didn't really establish that archaea was a separate group until the mid-'80s, with the advent of molecular biology, he says. "Originally, I think the guy used the term 'archaea' because he was thinking these were ancient-type bacteria, but actually the ones we see today are pretty modern organisms. They have their own niche—the ability to live in extreme environments. Molecularly and genetically they are unique and because a lot of archaea haven't been isolated until recently, there's a whole big area, a whole brand-new biochemistry, out there to be studied."

DeMoll says one application for extreme thermophiles is in polymerase chain reaction (PCR), a common laboratory technique for reproducing specific DNA sequences. PCR can produce millions or billions of copies of a piece of DNA in a few hours. "There's one step in PCR where you need to heat up the sample, so it's convenient to have an enzyme that's not killed by the heat," he says.

"Methanogens live in swamps, in your gut, in digestive systems of different species—but in all of these environments methanogens are anaerobic and produce methane to get their energy," DeMoll says. "The main reason I started looking at methanogens was my postdoc mentor at NIH, Thressa Stadtman. She was one of the first people to actually study these in the late 1940s."

DeMoll recalls that when he began his research in the early '80s, not much time had passed since the OPEC boycott caused fuel prices to skyrocket. "The Department of Energy was created, and one of their focus areas was basic energy sciences. It included a little group called energy biosciences, which was interested in funding research on energy production through biological means," he says. "Since methane is natural gas, I thought, 'Heavens, I've been looking at the biochemistry of methanogens for four-and-a-half years.' The energy biosciences group funded that work."

Many methanogens grow on a single carbon source like carbon dioxide, DeMoll says, and his goal is to explore the enzyme that facilitates the synthesis of one-carbon compounds into a two-carbon compound. "They need a source of electrons, too, so a lot of methanogens take carbon dioxide and hydrogen and make methane out of it. The enzyme complex involved here fixes carbon dioxide through a unique mechanism that doesn't evolve oxygen, and this is something we haven't found in the rest of the world."

This enzyme complex is also involved in the reverse reaction—breaking down two-carbon compounds into single-carbon compounds to produce methane. DeMoll says of the five proteins in this enzyme complex, three have novel catalytic activities. His current research is focused on revealing the structure and mechanisms by which these proteins work.

"To do this research we use 'glove bags' because we have to work in the absence of air," DeMoll says. "Before these tools were developed, we had to work in a room filled with nitrogen. We had to wear breathing equipment and work in pairs because of the danger. It was pretty eerie, because all you could hear was your own breathing."

DeMoll has been collaborating for the past three years with a number of other researchers, including fellow UK scientist Robert Perry in microbiology and immunology and Christopher Walsh, a biological chemistry and molecular pharmacology researcher at Harvard Medical School. Walsh's work is focused in the same area as Perry's and DeMoll's, so he wanted to come to Lexington to meet up with them. "Just coincidentally, Chris's sister lives in Lexington, too—in the same neighborhood where Bob and I live—so Chris has both professional and personal reasons to come to town," DeMoll says. The three researchers are currently involved in a project based on Perry's findings about the organism that causes bubonic plague.

"Iron is not very widely available in the environment, so many of the bacteria that cause disease have to scavenge for iron once they get into the body. They make these little compounds that go out and steal iron from various parts of our body and bring it back to the bug. Bob found out that by the natural route of infection the organism that causes bubonic plague wasn't virulent—when he mutated the genes responsible for a certain kind of iron uptake, it did not cause disease. The National Institutes of Health was very interested in this," says DeMoll.

"Though we don't have a bubonic plague problem in the United States, it's a good model of disease so that's why we study it. The Army is interested in it because a lot of places they go, they have to worry about plague."

DeMoll says his role in this project is to explore the fundamental catalytic mechanisms—the way enzymes stimulate reactions—when the bubonic plague organism enters the body.

He sums up his research in three goals: 1) learn about new types of catalysis and uncover new chemistry to create and break down carbon compounds, 2) improve methane for heating applications (manure ferments and produces methane that farmers can use for small-scale heating), and 3) reveal the mechanics of each step in enzyme reactions.

DeMoll points to the research project he did in his senior year at the University of Texas at Austin as the experience which led him to his current career. "One of the most important things a student can do is undergraduate research," DeMoll says. "My research project was really the first exposure I got, and it proved to me that science was a lot of fun."

Problem-solving through enzyme engineering
She came to the University of Kentucky to solve a "two-body problem," says Anne-Frances Miller, an associate professor who spent almost seven years at Johns Hopkins University.

"My husband had been promoted at Boston University, and I'd been promoted at Hopkins, but I couldn't get a job in Boston and he couldn't get a job near Baltimore. So the University of Kentucky was able to come up with two tenured positions and the apparatus I needed," Miller says. "This is a really smart thing for a place like UK to do—exploit the fact that they have more than one position open to get two people at once. You'll get people you might not otherwise get, and moreover once you've got them, you're less likely to lose them because neither one will leave without the other. More institutions should clue into this." Miller and her husband Ganpathy Murthy, an associate professor of physics, came to UK last summer.

"UK is very attractive in terms of colleagues, and the equipment and research support was crucial. It's suicide to go somewhere that won't give you support," she says.

Miller praises Boyd Haley for what she calls energetic and forward-thinking leadership. "His willingness to shake the system into trying something new is very important because institutions that aren't prepared to toss out the old as soon as it is outdated, if not before, will go the way of the dinosaurs. They may persist as teaching institutions, but they will not succeed as research institutions. You need gutsy people in the higher offices, people who are willing to evaluate risk after risk instead of retreating to the comfort of what has been done before," says Miller, who earned her Ph.D. in biophysical chemistry from Yale and conducted postdoctoral research at MIT.

Photo of Joseph Walsh, Ronald Keder, Emine Yikilmaz, and Anne-Frances Miller(Left to right) Graduate students Joseph Walsh, Ronald Keder and Emine Yikilmaz followed their professor Anne-Frances Miller (foreground) to the University of Kentucky from Johns Hopkins. In the background is one of several state-of-the art nuclear magnetic resonance instruments in the chemistry department's NMR lab.

Through grants from the American Cancer Society, NSF, NIH, and the Petroleum Research Foundation totaling more than $1 million since 1993, Miller has been utilizing nuclear magnetic resonance (NMR) to study enzymes.

"NMR reveals chemical functionality," she explains. "We take advantage of the fact that the nuclei of naturally occurring atoms emit very weak but extremely informative signals. In the example of my own research, the enzyme superoxide dismutase has 2,000 hydrogen atoms in it, with 2,000 separate protons—each with its own signal, each one giving you information about what a corner of the molecule is doing. It's very rich information and, moreover, it's site specific. You can map what each individual proton is experiencing."

In the simplest terms, Miller's work focuses on the movement of electrons. "Electrons are minute, fundamental particles. Enzymes, which are great big proteins by comparison, are able to manipulate exactly where electrons go, and how much energy is involved in these transactions.

"The amount of energy the protein itself can leverage on these electron movements is something, as chemists, we call the 'redox potential,'" she says. "Superoxide dismutase gives and takes electrons onto the metal ions in the enzyme. The higher the redox potential of that ion, the more avid an electron receptor that ion will be." In a lot of cases, says Miller, she wants to reverse this process so that instead of accepting electrons a metal ion will act as a donor.

"We can go in and modify the protein slightly and dramatically alter the chemistry that the enzyme will execute." The goal, she says, is to engineer enzymes to do novel chemical reactions through very minor changes to the original proteins.

"We've been able to take an enzyme that normally activates manganese, make a single change, and now it activates iron. The reverse change," she says, "is perhaps the more clinically useful one. Iron is a little bit toxic, and manganese isn't, so you would take an enzyme that uses iron and have it use manganese instead.

"The enzyme's job is to focus the metal ion on one particular reaction—and this is really the hallmark of enzymes as catalysts, they are very specific," Miller says. "There are a lot of catalysts that do a perfectly decent job accelerating a reaction; frankly iron alone without the whole protein accelerates the reaction very, very well. But most metal ions catalyze many reactions.

"A cell has a thousand reactions going at once, and they need to occur in synchrony and harmony—you can never afford to build up one compound and not have enough of another, so reactions have to be tightly controlled and highly specific. You can"t have iron running around doing a dozen reactions willy nilly. Control is what the protein brings to you," Miller says. "Because protein enzymes like superoxide dismutase are exquisitely specific, it?s safe to administer a fair amount of this stuff to a patient. You don't need to worry about by-products, side reactions, or other unintended activity."

Miller says she is focusing on superoxide dismutase because it is the little cousin of a number of other more complex enzymes that catalyze clinically, environmentally and industrially important chemical reactions. "What we'd really like is the option to choose the metal that is most useful and adapt the protein to do whatever chemistry we desire. Superoxide dismutase is a great model for learning exactly how we can go about doing that."

This research has sweeping applications. "Pain relief, inflammation, arthritis, auto-immune disorders, spinal cord damage—the possibilities go on and on," Miller says. "A lot of people are already looking at oxygen free-radical damage. The loss of function after spinal cord injury is largely related to damage after the injury, not during the injury itself, and often that damage is the result of uncontrolled oxidative reactions." Oxidation simply refers to any chemical process that removes electrons from a molecule.

"Many, many diseases have an oxidative damage component," she says. "Superoxide dismutase can prevent all that. UK has a lot of strength in this area."

Miller's research also reaches into the area of waste detoxification, breaking down toxic pesticides, herbicides and PCBs. "We work very hard in my lab to not get pigeonholed into something too specific," she says. "I don't need to be the world's expert on some itty bitty corner of something virtually irrelevant. I want my work to be of interest and of use to as big a community as possible."

Miller says the public needs to be well educated about biological chemistry and biotechnology. "We're seeing the fruits of these technologies on a day-to-day basis," she says. "Genetically engineered crops and animals, genetic therapies for congenital diseases, genetic production of drugs—decisions we make every day should be based on a good education in these areas.

"The rampant fear of genetic engineering is dangerous. It produces inappropriate action, knee-jerk responses, to a technology that has enormously powerful possibilities. This sort of blind fear is completely unnecessary—biotechnology is extremely exciting, and it's not inaccessible to the public. We all stand to benefit a lot as long as we inform ourselves to make wise decisions," says Miller. "There are people who don't want to touch genetically engineered food in the grocery store, but they'll happily pour Drano into their toilet. It's a completely ill-founded comfort level, and it's a fault of our education system that this kind of misunderstanding persists."

Miller says UK students in the new biological chemistry program will be well prepared for the new world of biotechnology. "We've given some serious thought to trying to put together a group of courses that will give an advanced undergraduate or entering graduate student a solid foundation. Our students should come out with a working knowledge, a working comfort, and an aggressive excitement, because biological chemistry will be a real part of their future," Miller says.

"If they're ready to step in with confidence and a good understanding, they'll have a lot more options available to them and they'll be more sought-after. My own students are getting into law firms, the patent-trademark office and industry at a number of levels because of the comfort and familiarity they have with this new area."