Robots Eavesdrop On Cellular Discussions

Using robots to monitor the goings-on of thousands of individual baker's yeast cells growing on a small plastic grid, scientists supported by the National Institutes of Health, in collaboration with CuraGen Corporation of New Haven, Connecticut, have accomplished a biological milestone in determining which molecules in a cell "talk" to others by making physical contact.

Without an automated approach, the job of looking -- one by one -- for all the physical contacts among the protein products of the thousands of genes in a yeast cell would be a painstakingly slow process.

Even though the researchers detected only a fraction -- roughly a thousand -- of such physical contacts, the impact of the new approach is expected to be significant.

"Scientists all over the world working in yeast will be able to use this information," said Dr. Stanley Fields of the University of Washington, one of the paper's senior authors. The work appears in the February 10 issue of Nature, and is featured on the cover of the journal.

Baker's yeast -- known to researchers as Saccharomyces cerevisiae -- is a laboratory darling to thousands of scientists who probe mysteries of biology, a large number of which are germane to understanding human health and disease. Though primitive, yeast cells share an extraordinary number of important similarities with more highly evolved species, including humans.

"Listening in" on which proteins physically talk to other proteins is a critical task for researchers, since all cells rely on extensive and ongoing molecular discussions to carry out life's functions -- everything from breathing to memory.

Other scientists have developed powerful approaches to determine which of the thousands of genes are "turned on" in a particular cell, but they haven't had a "guide book" to tell them which gene products likely touch each other.

"Now they have one," said Dr. James Anderson, a molecular biologist at the National Institute of General Medical Sciences, one of the NIH components that funded the study. "Dr. Fields' work adds an essential piece to the puzzle posed by genetic information that appears to be an enormous jumble of letters and words," he added.

Imagine, for instance, visiting a library full of books that you couldn't read. In a sense, this is the scientific dilemma facing biologists across the globe. Researchers have in hand boatloads of genetic information--billions of DNA letters that spell out the instructions for life in organisms as diverse as yeast, worms, flies, and humans. The problem is that, to a great degree, no one knows what all these genes do. And even in the cases where scientists do know, even more puzzling is how cell parts communicate with each other, often through physical contact.

Dr. Fields' team and their CuraGen colleagues accomplished the work by automating state-of-the-art, but commonly used, molecular biological techniques. The researchers used two separate approaches to attack the problem. Each was an automated strategy in which a test cell only survives if it contains proteins that touch each other.

According to Dr. Fields, the key element underpinning their current research tour de force was the availability of the entire DNA sequence of the genome of baker's yeast and the ability to recognize the genes. When the complete sequence of the human genome is available to researchers in the next couple of years, Dr. Fields predicts, a similar strategy will be possible using human cells.

"It's just a matter of scaling up," he said.

In addition to NIGMS, NIH's National Center for Research Resources (NCRR) also provided funding for the work, along with the Howard Hughes Medical Institute and the Merck Genome Research Institute.