Drugs for Genetic Disorders
Johns Hopkins Biomedical Engineer Analyzed
Protein Interactions Within Bug Cells
A Johns Hopkins researcher played a leading role in the creation of a landmark map detailing the way proteins interact within fruit fly cells. The map provides a model for future studies in humans that should lead to a better understanding of genetic disorders and infectious diseases. The research also opens an important new door toward identifying drugs for treatment of such ailments. The paper will be published online by the journal Science at the Science Express web site on Thursday, Nov. 6. (See www.sciencexpress.org and also www.aaas.org.)
Earlier research had provided a list of the 14,000 genes within a fruit fly and the proteins they produce within the insects cells. "That's like having a biological 'parts' list," said Joel S. Bader, an assistant professor in the Department of Biomedical Engineering. "But what we haven't known is how these parts are connected to one another. We haven't had the equivalent of a wiring diagram or an assembly manual. What this new map does is tell us which proteins 'talk' to one another and work together within the cell. We've only had maps like this for single-cell organisms like yeast. This is significant because it's the first large-scale assembly diagram for a multi-cellular organism."
With more than three dozen colleagues, Bader began working on the map several years ago as director of bioinformatics at CuraGen Corp., a biotech firm based in New Haven, Conn., where most of the research was carried out. He continued working on the project after joining the faculty of the Whitaker Biomedical Engineering Institute at Johns Hopkins in August. Bader is one of three lead authors of the Science paper detailing the protein interaction map. He said the map produced for the fruit fly, or Drosophila melanogaster, can serve as a template that can be followed for other species, including human beings.
"This is a milestone because one of the things that's been missing from the advances in genome sequencing is that we haven't known what each gene does," Bader said. "It's not enough to know which parts make up a human cell. You have to know which parts work together to carry out particular functions within the cell. This will lead to a better understanding of genetic diseases, and it will add to our knowledge of basic biology, our understanding of how cells work." The fruit fly has been a favorite model for genetics researchers for almost a century because the insects are small, easily bred and have a generation time of only about two weeks. Fruit flies and humans share developmental similarities, and biological processes are even more similar at the cellular level.
To find out which proteins expressed by fruit flies genes interact with others, Bader and his colleagues employed a technique called the two-hybrid method, in which they "mated" specific types of yeast cells. In each experiment, a yeast cell carrying just one fruit fly protein was mixed with yeast cells carrying about 10,000 other fruit fly proteins. By examining the offspring that survived this "marriage," the researchers could determine which proteins interacted with one another. The experiment had to be repeated 10,000 times to generate enough data to produce the interaction map. The large research team included people who conducted the lab experiments, others who organized the massive amounts of data and still others — including Bader, a specialist in computational biology — who analyzed the data.
The results of the fruit fly protein interaction map research will be stored in databases that will be publicly accessible to other scientists via Web sites. Bader is using the map in a collaboration with infectious disease experts to understand how our cells combat microbial pathogens. Bader believes other researchers will use the data to learn more about the workings of living cells and to locate drug targets that may be useful in the treatment of illnesses that may have a genetic component, including cancer, neurological disorders and diabetes.
Note: Color image of Joel Bader available; Contact Phil Sneiderman.
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