A disordered thermostat  pg. 4

How are scientists able to tease out the elements of this complex network of interactions? Here are some of the ways:

Gene microarrays

The recent sequencing of the human genome (and those of other animals) is just the latest in a series of critical advances during the past quarter century that have enabled scientists to identify specific genes, map their location and determine what they do.

In just the past three or four years, researchers have figured out how to monitor the expression of thousands of genes simultaneously by spreading complementary bits of genetic material across a glass slide, called a microarray. Active genes will bind to the array in a way that can be can be detected by fluorescence and other tagging techniques.

This sequence of images, showing beta cells in an isolated mouse islet becoming more metabolically active in response to glucose, was created using two-photon excitation microscopy. The technique monitors the rise in the autofluorescence of NADH, one of the molecular byproducts of metabolic reactions. The final image in the sequence shows an islet stained with antibodies that attach to the beta cells (green) and the alpha cells (red).
Courtesy of David Piston, Ph.D.
“We’re not after single genes anymore,” explains Leibel, head of the Division of Molecular Genetics and co-director of the Naomi Berrie Diabetes Center at Columbia University. “We’re after the interaction of multiple genes … We’re trying to study the whole biology.”

Thanks to a recent initiative supported by the National Institute of Diabetes and Digestive and Kidney Diseases, researchers at Vanderbilt and elsewhere are creating pancreas-specific microarrays – chips the size of a saltine cracker that contain all of the genes expressed over the life span of the beta cell in mice and humans. This method allows scientists to determine which genes are turned “on” or “off” in pancreatic cells, and it has aided the discovery of previously unidentified genes that play a role in the development of pancreatic islets, Magnuson says.

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