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Scientists get look at genes' defensive playbook<
by: John Pastor
Using a new method to identify networks of infection-fighting genes, scientists writing in a recent online edition of Nature say more than 15 percent of our genes are mobilized to defend against microbial attacks. The body's overwhelming genetic defense, which has implications for the survival of patients who are severely burned or injured, was revealed in a sweeping analysis of gene activity in volunteers who were injected with a bacterial product that temporarily created flu-like symptoms. "During a 24-hour period, the expression of more than 3,700 genes changed in blood leukocytes," said Lyle Moldawer, Ph.D., a UF College of Medicine professor of surgery, part of the national consortium that published the findings. "It was a dramatic reprioritization of genes. But beyond individual genes, we were able to look at networks, or functional modules of different gene clusters, that change in concordance with one another. We have now identified previously unknown relationships among different genes that tell us in greater detail how blood cells respond to an infectious challenge." "This work represents a major step in understanding inflammation in severely injured or burned patients," said Jeremy M. Berg, Ph.D., director of the National Institute of General Medical Sciences, the component of the National Institutes of Health that funded the research. UF Genetics Institute researchers are part of a national group of scientists united by a five-year, $37 million "glue grant" from the NIGMS. Glue grants bring together scientists from diverse fields – in this case, surgery, critical care medicine, genomics, bioinformatics, immunology and computational biology -- to solve problems in biomedical science that no single laboratory could address. Scientists injected healthy volunteers with a microbial product that temporarily causes nausea and fever, triggering natural immune responses. The condition is similar to sepsis, causing "Basically we made the volunteers appear septic for a couple of hours and examined changes in the gene expression from their white blood cells," Moldawer said. "Such genomic analyses give us the ability to simultaneously survey the activity of every gene in the cell, giving us vast lists of genes that change in response to stimulation. It provides us with an unprecedented amount of data." To make sense of the enormous amount of information, researchers plugged their list of nearly 4,000 gene changes into a database of interactions of known human and mouse genes developed by Ingenuity Systems Inc. of Mountain View, Calif. The results identified the networks of genes that helped the body respond to the challenge. "We were able to identify changes in functions that we never would have seen before," Moldawer said. "For example, the ability of the infection-fighting cells to make energy appeared to be down-regulated, as if the cells were shutting down all other functions not required to With that knowledge, scientists may be able to look at new ways to re-establish stability within the cells and avert the negative consequences of infection fighting. "The apparent repression of genes that occurs has never been fully appreciated," said Henry Baker, Ph.D., associate director of the UF Genetics Institute and director of the UF lab that performs genomic analyses for the consortium. "Initially, more than half of the genes became less active, but over th< |
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