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	Microarray "Heat Map" This diagram (top right) indicates which genes are active and which are passive in response to experimental stimuli. Red indicates strong activity (upregulated) and Green indicates reduced activity (downregulated). Microarray Chip Chips such as this can probe more than 6 million unique gene sequences. (bottom center) A microarray scanner. (bottom left)		ISB RESEARCHERS DEVELOP NEW METHOD FOR UNDERSTANDING WHEN AND HOW IMMUNE SYSTEMS PROTECT AGAINST INFECTION      Researchers at the Institute for Systems Biology have developed a new computational framework that helps them better understand the molecular "sequence of events" triggered when an immune cell detects a virus or bacterium.      Understanding that sequence of events is critical if researchers are to identify points in the process that can be targeted with new and better drugs designed to address immune-related diseases. In addition, understanding how an immune cell responds to a virus or bacterium could lead to improved vaccine designs. A paper describing this computational framework was published on March 21 in PLoS Computational Biology.      "This research involved integrating many different types of biological data, and in particular time-course gene expression measurements, using an approach that is unique in the context of primary innate immune cells in mammals," said Stephen Ramsey, PhD, a senior research scientist at ISB and an author of the PLoS article.      Much of mammalian systems biology research is conducted using cloned cell lines, rather than "primary" cells. Primary cells more closely reflect cellular conditions found in live organisms, but they are more challenging to use from a research perspective.		This research effort is part of a $50 million contract from the National Institute of Allergy and Infectious Diseases to conduct the first ever systems biology study of the innate immune system. This component of the research involved developing and using new computational methods for predicting the correlation between transcription factors (proteins which cause certain genes to turn on or off) and gene activation within the macrophage (a cell in the innate immune system that attacks pathogens and recruits a variety of immune cells) in response to a foreign threat. Which genes are turned on or off determines the physiological action taken by the macrophage. Researchers then validated the predictions using a different molecular measurement technology.      The newly developed framework is a useful tool for obtaining new and important information regarding innate immune molecular processes, which can then be validated using targeted experiments, according to Ramsey.      "The development of this framework directly demonstrates the value of a systems approach to biological research," said ISB Associate Professor Ilya Shmulevich. "Mathematicians, cell biologists, geneticists, engineers and more worked together to generate findings that would not have been possible without interdisciplinary collaboration that serves as the foundation of ISB."
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