LSI challenging the norm

A different way of doing science. Collaboration across many fields of science and medicine. These have been the promises of the Life Science Institute (LSI) since it first was proposed in 1998. But as researchers have signed on to become part of the institute, and as the space for their collaboration is being occupied this fall, the dream has become reality.

At a media day Oct. 14, LSI Director Alan Saltiel helped reporters understand the concept of multidisciplinary science, using his research in diabetes as case-in-point.

The incidence of diabetes in the United States continues to rise, with somewhere between 8 and 10 percent of the population affected, Saltiel said. Most alarming, he said, is the growing number of children with the disease.

Science has come a long way in being able to identify the genes responsible for a disease such as diabetes, he said, but much more needs to be learned about where our genes start and stop; how they are turned off and on; how the genetic material that relates to a particular disease is regulated in order to express itself symptomatically; and how the gene relates to the manufacture of the proteins which give us our characteristics.

"The biggest challenge is that no one investigator can ask these questions by him- or herself," Saltiel said. This is where the collaboration comes in.

What is known about diabetes is that it is genetic, as partly evidenced by studies showing the disease in 90 percent of identical twins who have an affected sibling, Saltiel said. What geneticists still are trying to determine is if the genes they have identified for diabetes make us susceptible to the disease, or if those genes actually protect us from it, so they conduct experiments where they attempt to manipulate the genes to over-express the disease.

But geneticists can't study the phenotype—visible properties of an organism—themselves, Saltiel said, so they call upon a physiologist, who also can offer an explanation for how sugar is disposed of in cells. Diabetes is characterized by excessive amounts of sugar in the blood and urine.

"Then a cell biologist comes in to talk about how sugar is stored in fat cells," Saltiel said. Cell biology is Saltiel's area of expertise, and he studies how insulin signals the mechanisms that cause fat cells to take sugar out of the blood stream.

A structural biologist could then be consulted to look at the shape of a protein and note any changes in it. The next expert to be brought into the discussion might be a biochemist, Saltiel said, who can study the activity of the protein to see what goes wrong in diabetes.

"Finally, a chemist comes in and finds the chemicals that bind to the protein to change its function. This is the beginning of drug discovery," he said.

"Ultimately to modify a disease state, you have to understand the physiology of the normal state and the pathology of the disease state," Saltiel said.

Senior research scientist Kun-Liang Guan, the first to move his lab into LSI, told reporters he looks forward to the collaboration with other colleagues, and already has identified a researcher on the LSI faculty whom he expects to consult about his study of tuberous sclerosis, a rare genetic neurological disorder primarily characterized by seizures, mental retardation, and skin and eye lesions. Guan has been studying genes that regulate cell size, and his work has crossed paths with some Cincinnati researchers using the drug Rapamycin to suppress the tumors associated with tuberous sclerosis. Guan understood the pathway upstream of where Rapamycin was working, but he hadn't recognized the link to the disorder downstream. Now both research teams know more. Having colleagues from different fields just down the hallway should lead to more such serendipitous co-discoveries, Guan said.

Saltiel said the unique multi-faceted structure of the institute is not for everyone, but he is confident he will be able to recruit 25 men and women who will find excitement in an environment that flies in the face of traditional science.

"We want people to do research where they challenge the dogma," Saltiel said. "We expect an environment of organized chaos—one that requires people to be somewhat disrespectful of traditional ways. This is going to be a different way of doing science."

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