Scripps Research Wins $51 Million Contract to Study Critical Immune Response Mechanisms

By Eric Sauter

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has awarded a $51 million five-year contract to The Scripps Research Institute to study innate and adaptive immune responses to a number of pathogens, including the influenza virus.

Richard Ulevitch, Scripps Research professor and chairman of the Department of Immunology, will lead the project as principal investigator.

The project's long-term goal is to develop innovative approaches to improving vaccines and immunotherapeutics that can be used against a wide range of diseases, particularly emerging or reemerging infectious diseases.

"This represents a significant investment in an absolutely critical area of research," Ulevitch said. "Understanding immunity at this level is the key to treating human inflammatory and infectious diseases."

Consortium members sharing in the multi-year contract are the Institute for Systems Biology (Seattle, WA), the Australian National University (Canberra, AU), and Stanford University (Palo Alto, CA).

The new contract builds on a previous five-year program to develop a comprehensive and detailed picture of innate immunity, the body's first line of defense against infectious diseases. That program was awarded a $24 million grant by NIAID in 2003.

"The complexity of the underlying biology requires an experienced scientific team with an advanced understanding of innate and adaptive immunity to infection," Ulevitch said. "We have that team in place. More importantly, we have a well-established record of close collaboration, and a history of important scientific discoveries."

Toward an Overarching Understanding

Using microbial pathogens, the consortium will develop a detailed model of innate and adaptive immune responses to infection in animal models, and confirm that similar pathways function in primary human immune cells.

With the new contract, Ulevitch noted, the scope of the project has expanded significantly and the group has increased resources by adding a second Forward Genetics group, which will screen mice mutants for defects in innate and adaptive immune responses, and a Signaling Core, which will elucidate gene regulatory and signaling networks that control the immune response to pathogens. 

The new research will apply a systems biology approach to identify the complex cast of characters that make up the innate and adaptive immune system. Systems biology is a relatively new field that blends genomics and proteomics with mathematics and computer modeling to gain an overarching understanding of the entire biological system.

In contrast to traditional hypothesis-driven research, in which a single gene or protein is selected for study, the consortium scientists will first gather information about multiple genes, proteins, and biochemical reactions without regard for function—and then examine this data from multiple perspectives to understand how the full system functions. Using a range of analytic tools, including mass spectrometry and transcriptome profiling, they will determine the biological role of these regulators.

The systems biology-driven program of gene discovery and network analysis will be implemented by groups at the Institute for Systems Biology in Seattle and at Stanford University.

"The resources of the Institute for Systems Biology are absolutely critical in implementing this complex approach," Ulevitch said. "Through its resources, and those of Stanford University and Australian National University, we have the large-scale analytical tools and computational approaches to facilitate gene discovery."

The studies will also include state-of-the art analysis that determines the relevance of these genes to human immune responses. "We understand that translating the findings from mouse models to human cells is a complex challenge, one without a single solution," Ulevitch said. "As a result, we're taking a multi-track approach to the problem that we believe will allow us to demonstrate the potential usefulness of these newly discovered immune mechanisms to treating infectious diseases in humans."

As the research progresses, the consortium will provide a Web-based data portal to enable the scientific community at large to access the findings without specialized training in informatics or computational analysis.

In addition to Ulevitch, the consortium includes: Alan Aderem, co-founder and director of the Institute for Systems Biology; Bruce Beutler, chair of the Department of Genetics at Scripps Research; Christopher Goodnow, director of the Australian Phenomics and Immunogenomics Laboratories at the Australian National University; Garry Nolan, director of the Stanford National Heart, Lung, and Blood Institute Proteomics Center; Ilya Shmulevich, director of Computational Biology the Institute for Systems Biology, and Luc Teyton, professor in the Department of Immunology at Scripps Research.

Send comments to: mikaono[at]scripps.edu

The $51 million National Institutes of Health contract, led by Scripps Research Professor and Immunology Chair Richard Ulevitch, will fund research on innate and adaptive immune responses to a number of pathogens, including the influenza virus (above).