This work builds upon research reported by Young in the journal Science in October 2002, in which he mapped the general locations of approximately half the gene regulators in yeast.
"The results of the Science paper were pretty low-resolution," says Young. "We were only able to identify in a general way regions where these gene regulators landed. In this paper, we've located all 203 regulators in yeast," and using tools developed in Fraenkel's lab have also been able to nail down the exact landing points. As a result, scientists now can begin to understand how genes and their regulators "talk" to each other. According to Fraenkel, knowing these communication patterns ultimately will have a profound influence on our understanding of everything from infectious disease to cloning.
To eavesdrop on these cellular conversations, graduate student Chris Harbison from Young's lab and postdoctoral researcher Ben Gordon from Fraenkel's lab combined the latest biological tools with new computational methods.
Harbison took yeast cells and subjected them all to a dozen nutritional, chemical, and temperature environments. "We tried to come up with different conditions that a yeast cell would encounter in its natural habitat," says Harbison.
Gene regulators come out of hiding and do their job in response to environmental conditions, but they don't all respond to the same kinds of predicaments. Running the cells through a wide spectrum of stimuli was a way of waking up all the regulators--in a sense, shaking the bushes and then nabbing them once they're out.
Next, Harbison placed gene fragments associated with these regulators onto a series of microarrays--small dime-sized silicon or glass chips that contain thousands of pieces of DNA--which allowed him to come up with a list of approximate locations. Gordon and Fraenkel created computer algorithms that fused Harbison's data with data from other yeast species i
Contact: David Cameron
Whitehead Institute for Biomedical Research