Scripps Research Institute scientist to uncover workings of the immune system

A team led by a scientist at The Scripps Research Institute has received a $22.5 million, five-year project renewal from the National Institutes of Health to uncover the workings of the immune system. This program has received ongoing support from NIH since 2002.

The grant is focused on innovative technologies that will ultimately provide data for improving a wide range of human diseases that include viral and bacterial infections and inherited immune disorders.

"I'm delighted the National Institute of Allergy and Infectious Diseases has decided to continue supporting this important research," said the grant's principal investigator Richard Ulevitch, who is a professor and chairman emeritus at Scripps Research. "Since the initiative began 10 years ago, the consortium has made seminal contributions to the field. Now, thanks to the new funding, there are more discoveries to come."

The project takes an unusual wide-angle "genetic and systems biology" approach to learning how we stay healthy in the face of numerous microbes in our environment. In contrast to traditional hypothesis-driven research, in which a single gene or protein is selected for study based on its proposed function, team members assemble information about multiple genes, proteins, and biochemical pathways without preconceived ideas about function. This data is then integrated and examined from multiple perspectives to understand the immune response as a whole.

In addition to Ulevitch and his group at Scripps Research, the consortium includes the laboratories of Alan Aderem of the Seattle Biomedical Research Institute, Bruce Beutler of University of Texas Southwestern Medical Center, Christopher Goodnow of the Australian National University, and Garry Nolan of Stanford University.

Ulevitch notes that the group is now especially interested in the intersection between innate and adaptive immunity. Innate immunity, our body's first line of defense, can destroy foreign invaders and trigger inflammation that contributes to their demise. If microorganisms make it past this gauntlet, the body calls on adaptive immunity. Here, T cells, B cells, antibodies, and killer cells come into play; the adaptive immune system also stores "memories" of the offending microorganisms to be on the alert for future attacks.

The team is using a genetic approach in mice, known as "forward genetics," to develop a detailed model of innate and adaptive immune responses to infection. "It is now crystal clear that data from mouse genetics provides insights into human disease," Ulevitch said. "When we started there were a lot more unknowns, but now there is a long list of genes identified in the mouse that cause both specific mouse phenotypes and are similarly linked to human disease."