NIAID Funds $51 Million Contract to Create Comprehensive Model of Immune Responses

A team of scientists is expanding efforts to develop a detailed picture of immune system function with a new $51 million, five-year contract from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The research builds on a project originally funded by NIAID in 2003, and will continue to be led by Richard Ulevitch, PhD, of the Scripps Research Institute in La Jolla, Calif. The contract will also involve scientists from the Institute for Systems Biology in Seattle; StanfordUniversity in Palo Alto, Calif.; and the AustralianNationalUniversity, Canberra.

"The collaborators on this project have previously made significant contributions to our understanding of innate immunity, the body's first line of defense against infection," says NIAID director Anthony S. Fauci, MD. "They are well-positioned to generate knowledge that will advance the development of new treatments, diagnostics and vaccines for infectious diseases that occur naturally or are deliberately introduced into a population."

According to Ulevitch, the researchers will use a systems biology approach to build a comprehensive model of the immune system's response to several disease-causing agents. Systems biology melds established life sciences with informatics, computer modeling and new techniques of gene and protein analysis to generate a wide-angle view of entire biological systems. To date, the team focused on developing an encyclopedic account of innate immunity. Now, the project's scope will broaden to encompass components of adaptive immunity, which includes antibodies and a diverse class of immune system cells called T cells.

Ulevitch and his collaborators will create mutant mice and then screen them to find defects in the animals' innate and adaptive immune reactions to viruses, including influenza, mousepox and mouse cytomegalovirus, and to several bacteria, including Salmonella and Listeria. Next, the group will conduct a systems-level analysis of the multiple immune system signaling pathways triggered by infection. The expanded project also will include studies aimed at determining the relevance to humans of genes and pathways discovered in mouse models.

"We recognize that translating findings made with mouse models to their counterparts in the human immune system is a formidable challenge," says Ulevitch. "But we have in place a multi-pronged approach that we believe will allow us to validate our mouse findings in human cells."

Finally, notes Ulevitch, the consortium will develop a Web-based data portal that will give the wider scientific community access to the data, animal models, antibodies and other scientific tools expected to be generated over the course of the contract. The scientific community at large will be able to use the Web resources without any specialized training in informatics or computational analysis, he notes.

Source: National Institutes of Health

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