UNMC crystallographer maps protein structures

Gloria Borgstahl, Ph.D., is interested in far more than diamonds.

From her 10th floor lab in the Lied Transplant Center, the petite crystallographer

analyzes crystals, typically the size of a grain of sand, to map the structure

of human proteins. Her goal:  To better understand the structure and

function of proteins involved in DNA repair and to help other scientists

apply structural biology to their science in order to control and treat

a variety of diseases including cancer.

Its similar to fixing a car, said Dr. Borgstahl, an associate professor

in the Eppley Institute for Research in Cancer and Allied Diseases. You

first need to know what the engine looks like. Here, we need to visualize

the molecules.

Crystallography — the study of the atomic structures of proteins by

growing crystals of the protein and then collecting X-ray diffraction data

— has existed for decades. But, Dr. Borgstahl is one of the few X-ray

crystallographers with the background and ability to solve problems relevant

to the interaction of cancer cells with anti-cancer agents.

Its exciting to look at a structure no one has ever seen before,

Dr. Borgstahl said. Its like being an explorer — the discovery process

is most rewarding.

Dr. Borgstahl is a perfect addition to the cancer center and UNMC,

said Ken Cowan, M.D., Ph.D., director of the UNMC Eppley Cancer Center.

She adds specific expertise in X-ray crystallography, which is a critical

addition to our structural biology program.

Understanding the structure of key proteins in cancer is essential in

developing specific therapies for each cancer, Dr. Cowan said. UNMC and

the Eppley Cancer Center research effort are definitely strengthened by

the addition of Dr. Borgstahl, he said.

Dr. Borgstahl, who joined the UNMC faculty in August, also is among

a handful of researchers recently recruited through the tobacco settlement

funds that the Nebraska Legislature allocated to the states four biomedical

research institutions — UNMC, the University of Nebraska-Lincoln, Creighton

University and Boys Town National Research Hospital. In 2001-2002, the

Legislature allocated nearly $5 million to the UNMC Tobacco Settlement

Biomedical Research Development Fund.

This is my ideal job, Dr. Borgstahl said. Its close to home and

research is my first love. This is a perfect fit for me.

A native of Dubuque, Iowa, Dr. Borgstahl attended the University of

Iowa, where she earned degrees in biomedical engineering and biochemistry

and crystallography. She did her post-doctoral work in protein crystallography

at The Scripps Research Institute in La Jolla, Calif., and in molecular

biology at Los Alamos National Laboratory in Los Alamos, N.M.

In 1996, Dr. Borgstahl worked at the University of Toledo department

of chemistry, where she studied the macromolecules essential to the maintenance

and replication of DNA.

While there, she began working with NASA as a ground investigator and

had experiments flown to the International Space Stations Destiny laboratory.

The recent return of the shuttle brought back one of Dr. Borgstahls

experiments growing 133 separate crystallization experiments in space.

Crystals grown in microgravity are larger and physically more perfect than

those on the ground, she said. To invoke the crystallization process in

space, Dr. Borgstahl prepared the purified protein and a second formula

of buffers and salts.

The crystals, which will take several months to evaluate, will be photographed

under a microscope and exposed to X-rays in the Lied Transplant Center.

Then, a complete evaluation of crystal quality, compared to Earth-grown

controls, will be done with a synchotron, which provides a brilliant and

adjustable X-ray beam, called the National Synchrotron Light Source or

NSLS at Brookhaven National Laboratory in Upton, New York.

From the diffraction of the X-ray we can see the proteins structure,

said Dr. Borgstahl, the youngest of seven children. The crystal serves

as an amplifier for the diffraction signal from which the atomic structure

is deduced.

The information, which includes analyzing mathematical equations, helps

Dr. Borgstahl determine the three dimensional layout of the atoms and the

overall shape of the macromolecule.

Outside the lab, she and her husband, Daniel Kramer, enjoy spending

time with their two children, Marguerite and John.

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