September 23, 2008

Albuquerque Journal

Tiny Biology Big at UNM
By Olivier Uyttebrouck, Journal Staff Writer

Larry Sklar has figured out how to perform 4 million tiny biology experiments a year.
       
The University of New Mexico pathologist wants to increase that number to 10 million a year by 2010.
       
The National Institutes of Health recently awarded Sklar a six-year $15 million grant to test chemical compounds that one day could lead to new drugs and diagnostic tools.
       
The ultimate goal is to find new ways to fight enemies such as cancer, diabetes and infectious disease. The work also should help researchers unravel mysteries about how cells work, he said.
       
Sklar's invention, called high throughput flow cytology, allows researchers to screen large numbers of chemical compounds to see how they react with the basic elements of nature, such as proteins.
       
"The screening process allows us to see how these molecules work and see if they have features that will allow them to be useful in the biological world," Sklar said.
       
Sklar heads the New Mexico Molecular Library Screening Center. It is one of nine institutions designated by the NIH as "molecular discovery centers."
       
Sklar's lab at UNM's Health Sciences Center contains a "molecular library" about the size of a small refrigerator that stores about 200,000 chemical compounds at temperatures just above freezing.
       
The machine feeds the compounds into plates that each hold 384 "wells," pinprick-sized holes that contain biological targets such as proteins. Researchers then analyze the results to determine which compounds react with the targets.
       
The UNM center received a $9 million pilot grant in 2005. It tested 30 such targets during the pilot stage. Examples are:
       
• Efflux pumps. Cancer patients often die when their tumors become resistant to chemotherapy. Tumors can develop the ability to protect themselves from chemotherapy by using molecules called efflux pumps to transport the toxins away from the tumor.
       
• Quorum sensing. Bacteria have the ability to signal one another when they reach sufficient numbers to become harmful. Bacteria wait until they have sufficient strength, then switch into a more virulent form.
       
"We found molecules that block quorum sensing in bacteria," Sklar said.
       
During the three-year pilot project, robotics and data processing techniques were used to speed up the screening process, from about 5,000 tests per year to about 4 million. Sklar plans to increase the number to 10 million tests a year.
       
UNM has licensed Sklar's invention to IntelliCyt Corp., an Albuquerque startup firm that sells the equipment and software.
       
Pharmaceutical companies are taking a keen interest in the work, because it could point the way to promising drugs, he said. But Sklar doesn't call his work drug discovery.
       
"There's a long way between the discovery of a molecule with biological activity and use as a drug," he said.