Chipping Away at the Gene Code


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Expression of thousands of genes on a single chip
Newly arrived at the Weizmann Institute of Science: DNA chips -- built of the stuff that genes (and research dreams) are made of. Offering greatly improved means for probing the molecular roots of disease and examining fundamental questions in the life sciences, DNA chips are a key addition to the research "toolbox" of Israeli scientists.

The recently inaugurated DNA Chips Unit will serve as a nationwide resource for Israeli scientists and physicians. The unit is operated by the Institute's Crown Human Genome Center, headed by Prof. Doron Lancet, and the Department of Biological Services, headed by Prof. Menachem Rubinstein.

Pioneered by a California-based company called Affymetrix, DNA chips represent a striking interplay between computer science and biology. They look like the integrated circuits found inside a personal computer, but instead of containing tiny semiconductors, the thumbnail-sized glass chips are imprinted with thousands of bits of DNA. These fragments serve as probes, indicating the presence and activity of specific genes within the tissue sample, while operating at a fraction of the time and cost previously required.

"In contrast to former, single-gene evaluations achieved through a lengthy experimental procedure, DNA chips can monitor the expression (meaning the protein production) of thousands of genes at a time," explains Dr. Shirley Horn-Saban, who heads the DNA Chips Unit. They also offer a greatly enhanced method for detecting genetic mutations linked to disease onset, such as the p53 gene, mutated in nearly half of all cancer patients. "The powerful diagnostic capabilities offered by DNA chips will strongly influence medical practice, shifting the emphasis from detection and treatment to disease prevention," says Horn-Saban. Improved treatments may follow, since the technology makes it possible to comprehensively monitor the cell's response to treatment. Indeed, the expanded "perspective" offered by DNA chips should prove vital to changing the focus of genetic research from single gene functions to probing entire cells or tissues, adds Horn-Saban.

The Weizmann Unit is currently working in close collaboration with the Pediatric Oncology and Hematology Department at the Sheba Medical Center to improve the diagnosis and treatment of cancers prevalent in children, including neuroblastoma and leukemia. Additionally, the unit has put the chips to work on a variety of projects aimed at better understanding the genes involved in embryology and in cancer and other genetic disorders, such as Down syndrome. The Institute has recently purchased a complementary technology, called DNA spotting, which enables scientists to create custom-made DNA chips tailored to their specific research needs.

Bioinformatics Highways

Using DNA chips to obtain information about biological systems is only the first step. "The information delivered by the chips is so complex that effective interpretation requires elaborate data analysis and organization," explains Horn-Saban. Researchers at the Institute hope to address this challenge through computer and web-based technologies. They are working to link DNA results to GeneCards, an on-line database and software tool developed at the Institute that provides fast and convenient access to updated genetic information. Once a gene is identified from the DNA chip printout, the novel bioinformatics interface will provide a direct link to relevant information, including the proteins it encodes, cellular functions, diseases caused by its mutations, and other web sites. Another project, led by Dr. Naama Barkai of the Institute's Molecular Genetics Department, is aimed at using mathematics to interpret the function of highly complex gene expression patterns.

So -- the cast and backdrop are set: gene fragments in the thousands, mathematical tools, and bioinformatics highways revolving around a thumbnail-sized platform. These new technologies should dramatically fast-forward the unraveling of how genes influence the way we walk, talk, think, and succumb to disease.

Dr. Shirley Horn-Saban. Heading the Gene Chip Unit