Researching the
complex chemistry of life

By Kim MacQueen
and Frank Stephenson
FSU Office of Research

It's been called the Star Trek of basic research. The Human Genome Project, launched in 1990 by the National Institutes of Health and the U.S. Department of Energy, is a quest for unprecedented knowledge of the basic elements of human life.

The goal of the $3-billion, 15-year international research campaign is to determine the intricate layout of the chemical building blocks making up every human gene. The task is easily the most daunting genetic scientists have ever faced.

By around 2005, these scientists hope to have a blueprint of the entire human genetic code, a vast assemblage of information detailing the precise order of the chemical units that make each human gene unique. Scientists compare it to determining the sequence of letters making up every book in a large library.

Scientists generally agree that the end of the Human Genome Project will mark the beginning of the really heavy lifting in the long battle to understand how DNA and other molecules do the incredible things they do. With the complete genetic map in hand, the job becomes one of "reading" the vast, newly ordered blueprint and making sense of it. By then the job should be easier, thanks to gains being made in a young field known as structural biology.

Structural biology is now recognized as the key research specialty in a host of high technologies, from bioengineering to gene therapy. Biological-research centers everywhere are beefing up their profiles in the field amid near-daily news accounts of remarkable discoveries made in structural biology labs.

Florida State is no exception. In 1990, the university's Institute of Molecular Biophysics organized a structural-biology program. Jump-started with a $4-million gift from the Lucille P. Markey Charitable Trust in Miami, the program -- with seven full-time faculty researchers -- is now the largest of its kind in the Southeast.

Dr. Lee Makowski, director of the institute, has helped orchestrate its rapid development, guided by FSU's traditional strengths in physics, biology and chemistry. Makowski says the field is increasingly critical in transferring basic research to applications in medicine and industry.

"The driving force behind structural biology is the fact that it is very difficult to understand how a complicated machine works if you can't see a picture of it working," Makowski says. "We can now produce that picture, down to the level of every single atom, and use it to focus on questions that can make a difference in people's lives."

Since proteins are the engines that drive every biological process imaginable, structural biology has focused on the quest to link proteins' shapes and sizes to their myriad functions.

Last year, FSU hired a pioneer who has spent most of his career studying protein structure, and particularly how it figures into the creation of what is arguably mankind's sturdiest foe -- viruses.

Dr. Donald L.D. Caspar, an internationally recognized figure in structural biology, left Brandeis University to join the institute's new Program in Structural Biology. Makowski says Caspar helps put the institute on the scientific map and attracts top-flight researchers. Just this fall, the institute drew to FSU another prominent specialist in determining protein structure, Dr. Kenneth Taylor, formerly of Duke University.

"The NMR (nuclear magnetic resonance) facility here is among the best in the world," says Dr. Tim Logan, who uses it to study how and why proteins fold into various 3-D structures, the most vexing problem in the field. "There's a great core of people there, the support staff is excellent, and they have some of the best machinery in the world."

But for all their power and sophistication, today's tools seem almost crude when one considers the questions posed by even the simplest living organism. How is it that only a few lifeless elements -- mainly oxygen, nitrogen, carbon, hydrogen and phosphorous -- can come together in to create life? How can seemingly lifeless molecules move? Why do identical genes work in some places and not in others?

If nothing else, the rise of applications in biotechnology, a field unheard of 20 years ago, has demonstrated the value of basic research in structural biology. Sick people are being cured today with manmade drugs built an atom at a time, thanks to fundamental knowledge of molecular structure and behavior.

FSU researcher Dr. Michael Chapman is one of many structural biologists today who are intrigued by the idea of using viruses, for example, to fight cancer. He studies the atomic structures of harmless viruses that might carry good copies of damaged genes and deposit them wherever the body needs them. If a virus can be engineered to carry a good copy of BRCA1 -- the gene that predisposes women to breast cancer -- and drop it off at the right chromosome without being attacked by the immune system first, physicians would have a chance of stopping breast cancer before it starts.

"What all of us are trying to do here," he says, "is to use an understanding of molecular structure to improve health."