A comprehensive and detailed picture of innate immunity the human
body's first line of defense against disease is the goal of scientists
funded by a recently awarded five-year, $24-million grant from the
National Institute of Allergy and Infectious Diseases (NIAID).
Researchers at The Scripps Research Institute (TSRI) in La Jolla, CA, the
Institute for Systems Biology (ISB) in Seattle, and Rockefeller University
in New York are using techniques that straddle the divide between biology
and information science to fathom the workings of innate immunity. Knowledge
generated could help scientists develop treatments for septic shock, certain
autoimmune disorders and diseases caused by potential agents of bioterrorism.
Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology
and Transplantation, notes, "The collaborators at TSRI, ISB and Rockefeller
University have complementary expertise that is most impressive."
"Our goal is to develop an encyclopedia of innate immune system activity,"
says Richard J. Ulevitch, Ph.D., head of TSRI's immunology department and
the project's principal investigator.
As its name indicates, innate immunity is inborn and provides an all-purpose
defense against invasion. Innate immune system cells, including certain skin
cells called Langerhans cells, arrive soon after foreign elements are detected.
Some system components, called macrophages, find and engulf microorganisms,
while others release chemicals that kill the organism directly. Still other
cells begin recruiting specialized immune cells to the region.
Dr. Ulevitch and his co-investigators face a daunting task identifying
the thousands of genetic changes, proteins generated and biochemical pathways
triggered by encounters between innate immune system cells and infectious
agents. Unlike the highly specific antibodies, which are produced in almost
infinite variety and which match a particular disease organism like a key
in a lock, cells of the innate immune system react generically to a wide range
of substances, including molecules found in the cell walls of many kinds of
An encyclopedic account of these complex and interwoven processes requires
a systems biology approach, says Dr. Ulevitch. Dubbed "21st-century
biology," the relatively new field of systems biology melds mathematics,
computer modeling, and new techniques of gene and protein analysis in an effort
to gain a wide-angle view of biological systems.
Unlike traditional, hypothesis-driven biology in which a single gene or protein
is selected for study based on its proposed function, systems biology assembles
information about many genes, proteins and biochemical reactions at once without
regard for function. These enormous amounts of data are then integrated and
examined from multiple perspectives to learn how the system as a whole behaves.
Scientists at TSRI, ISB and Rockefeller University will focus on human innate
immune system genes that are turned either off or on when a cell meets an
infectious organism. Due to the high degree of similarity in the innate immune
systems in all animals, the scientists can employ mice to quickly determine
which gene groups deserve further exploration. Both the human and mouse genes,
for example, encode proteins involved in inflammation, a generic first response
to invasion by foreign organisms or to trauma. Uncontrolled inflammation can
cause extensive cell damage and even death. Better understanding of proteins
involved in the initiation and control of inflammation could help scientists
find targets for new drugs that can precisely modify the inflammatory response.
NIAID also recently awarded two contracts to support research in a key area
of systems biology, bioinformatics. Bioinformatics is the computational analysis
and organization of biological data such as gene sequences and protein structure.
The contract awardees, Research Triangle Institute in Research Triangle Park,
NC, and Northrop Grumman in Herndon, VA, will first assess the bioinformatics
needs of scientists working in such areas as transplant biology and autoimmune
diseases. The contractors will also develop and test a prototype system that
reliably and simply collects, stores and analyzes many forms of biological
data generated by multiple laboratories.
"The new grant, along with these new bioinformatics contracts, signals
NIAID's interest in advancing bioinformatics resources to support both basic
and clinical research on immune-mediated diseases," NIAID's Dr. Rotrosen
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.
NIAID is a component of the National Institutes of Health, an agency of
the Department of Health and Human Services. NIAID supports basic and applied
research to prevent, diagnose, and treat infectious and immune-mediated illnesses,
including HIV/AIDS and other sexually transmitted diseases, illness from potential
agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma