While many students complain about the prospect of enduring hours inside a laboratory, the work done by University researcher Dr. Wladek Minor, a professor of Molecular Physiology and Biological Physics, has caught the attention of fellow scientists around the world. Minor was honored with the distinction of having written the second-most cited research paper of the decade, according to The Scientist magazine.
In his 10 and a half years at the University, Minor has earned increased recognition for his work done in protein crystallography. His research and program development have made him a well-known innovator of the quickly growing field. Aside from traveling to places worldwide such as Brazil and China to teach and speak, most of Minor's work is done in his laboratory in Jordan Hall.
The advanced laboratory is equipped with numerous computers and machines that help the researchers with their work. In the important quest for both efficiency and accuracy, researchers at his laboratory use a complex computer network to organize and retain information. An integral part of this is the innovative use of personal digital assistants for which Minor's laboratory has received recognition in magazines such as Genomics & Proteomics.
Matt Zimmerman, Graduate Arts & Sciences student and researcher at Minor's laboratory, demonstrated the use of the PDA and indicated the advantages of using such a system. The researchers at the laboratory use the PDAs with an interface that helps them to make up solutions of various chemical content. The PDAs are linked to a wireless computer network and can calculate the concentration of the solutions needed and tell the technician exactly how much material to add. The incorporated barcode reader tracks the details of each chemical as it is used and prints out a specific label for each solution made. With this system, many avenues for experimental error are avoided.
"It's just your normal PDA, but we have software on it that allows us to eliminate trying to remember to write down data," Zimmerman said.
Aside from the PDAs and other scientific equipment, the laboratory's bright atmosphere is also equipped with a high-tech coffee machine and fancy Ferre Roche chocolates.
"We do fancy science, so we have fancy chocolate," Minor said.
The "fancy science" done at Minor's lab consists of various steps that researchers in the lab work to put together. Zimmerman said that each person continually tries to make each stop more efficient.
This drive has landed Minor in the second spot in the ranking of top scientific papers published in the last 10 years, according to The Scientist magazine. The paper titled "Processing of X-ray diffraction data collected in oscillation mode" was co-authored by Minor and Dr. Zbyszek Otwinowski, associate professor at the University of Texas Southwestern Medical School and Graduate School of Biomedical Sciences in Dallas. Published in 1997, it has since become the second-most cited scientific paper to be published from 1995 to 2005. Minor said that his paper gets about 250 citations per month.
The paper describes fundamentals of HKL and HKL-2000, programs created by Minor and Otwinowski. Minor said these programs allow for fast and efficient data reduction and analysis, which lead to elucidation of protein structures.
The work done by Minor's laboratory is part of a collaboration called the Midwest Center for Structural Genomics, the leading center of the National Institutes of Health Protein Structure Initiative. Minor said the Center aims to solve close to 1,000 structures by the year 2010 through making the process of protein structure determination faster and more effective.
Thanks to HKL-2000, work in protein crystallography has become significantly more advanced. Zimmerman said that before this new technology, solving a protein structure took, on average, six to seven years and often up to a decade. Without computer graphics, scientists used to map out structures on Plexiglas sheets that were then stacked together one by one to determine the overall structure.
With the HKL-2000, Zimmerman said that what used to take many years can now be done in a few days.
"We were at the Argonne Lab in Chicago on Monday collecting data, and by Thursday we were able to deposit two solved protein structures in the Protein Data Bank," Zimmerman said.
Minor said his lab has mapped over 375 proteins using his program and that it was reported that 78 percent of the protein structures identified in the Protein Data Bank were identified using HKL-2000. He said his program is now used in about 1,500 laboratories worldwide.
The significance of these numbers is due to the growing importance of identification of protein structure in science.
"You can see from the list of top papers that five of the top 10 are about structural biology," Minor said. "This is a very important topic to a lot of scientists."
Identification of protein structure allows for developments in medicine that could make great impacts.
"Right now, you can see how expensive drugs are," Minor said. "Using protein crystallography to look at protein structures and elucidate structure functions will result in an intelligent way to make new drugs that will be much cheaper and more efficient."
So how exactly does Minor's technology fit into protein crystallography, and why is it so popular? Despite the insistence from researchers such as Zimmerman and postdoctoral fellow Maksymillian Chruszcz that the process is much easier than before, the process is anything but simple.
Zimmerman said they start with proteins produced in bacteria such as E. coli. They extract the protein and, over a small reservoir of chemicals, they gradually increase the concentration of protein in precipitate until it drops out of the solution in crystal form. This process is done in varying temperatures of volumes of samples, and requires varied trials.
The crystals are then cooled to liquid nitrogen temperature and put into a strong X-ray beam. The diffraction data taken by this part of the process goes into Minor's computer program.
Unlike the Plexiglas method of old, Chruszcz emphasized the comparative ease with which protein structures could be solved using the program.
"You can solve a protein [structure] in as little as 10 minutes now," Chruszcz said.
He added that he had been working on a protein associated with leukemia and he hoped to identify the protein structure with the aid of the computer program. He hopes that this research will lead to new ways to cure the disease. Using the program, Chruszcz was able to carefully verify the data collected and map out the protein structure.
"You can see that it does this and checks our work very quickly, within a few minutes," Chruszcz said.
The various steps of the program allowed for a final presentation of the structure in the unit cell and the computer created a visual representation of the protein structure within minutes.
"After the computer does the work, we have to go back and check some of it," Chruszcz said. "We go and figure out where each type of atom fits."
The finished product is a three-dimensional representation of the protein structure that shows where atoms such as carbon and oxygen fit.
This meticulous process is done in many steps and the members of the lab collaborate to identify the precise structure. With the aid of the program, it can be done within a few days and the finished product is added into the Protein Data Bank along with other successfully identified protein structures.
The work done by Minor and his group is not contained within the walls of the laboratory and is not limited to the University Health System or the University itself.
"My lab is involved in many things throughout the entire world," Minor said. "Our work goes to many countries and I am always teaching students from all around the world about the latest developments in Virginia."
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