By the third day, the participants were amplifying DNA of the entire yeast genome. Then they took turns actually printing it onto the glass slides and examining the results. "This is cool," said Michael Ryan of the New York State Department of Health as he held up a slide to the light. "It's the first one that printed!"
The rest of the course focused on how to use the new machines. The students designed and carried out several experiments. They washed samples of DNA over the printed spots on the glass slides to see where the DNA would bind; binding indicated that a particular gene was expressed in the cell that provided the samples. They saw that various genes changed their levels of expression in different circumstances. And they learned how to measure and interpret these differences, using a special scanner for measurement and new software developed by Michael Eisen, a bioinformatics expert at Lawrence Berkeley National Laboratory, to identify patterns in the data. Eisen, who had already made his software available to all scientists, had come to Cold Spring Harbor Laboratory specifically to teach the participants how to use it.
The participants had many different reasons for wanting to master these techniques. "At least 20 genes are involved in juvenile diabetes, but for 18 of them we know almost nothingwe know only their general regions on chromosomes," said Michele Marron of the University of Florida immunology department. "Most of these DNA regions are very long and don't contribute a great deal. We hope to identify the genes by comparing levels of gene expression in normal and diabetic mice. We also want to identify the genes' pathways."
Christian Kaltschmidt of the University of Frieburg, Germany, who works on the mechanisms of memory, was eager to hunt for genes that may protect against Alzheimer disease. Matthis Lorenz of the National Cancer Institute in Bethesda, Maryland, is studying breast cancer. Maria Lagerstrom-Fermer of the University of Uppsala, Sweden, will compare gene activity in the cells of patients who have chronic myeloid leukemia during and after treatment.
Bruce Futcher of Cold Spring Harbor Laboratory will use the microarrayer he just built in the course to expand his work on the cell division cycle. In 1998, he collaborated with Paul Spellman, Pat Brown, and David Botstein to locate 800 yeast genes that are regulated by this cycle. Now he wants to study the clusters of genes that are turned on, one after another, during this cycle and to identify the functions of individual genes in the clusters.
In addition to doing their own research, nearly half the program participants intend to set up core facilities that will make and provide arrays for other scientists in their universities, hospitals, or research centers.
Once a microarrayer is set up, "it's so easy and cheap to make these things," says Pat Brown with missionary zeal. "You could print 100,000 arrays per year with four machines! It's so routine.... I wanted them to see it. I wanted to make sure they would not find it intimidating."
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