$24-Million Grant Funds Creation of Encyclopedia of the
Innate Immune System
By Jason Socrates
The National Institute of Allergy and Infectious Diseases
(NIAID) has awarded a multi-year, $24-million grant to a group
of researchers at The Scripps Research Institute (TSRI), the
Institute for Systems Biology (ISB) in Seattle, Washington,
and The Rockefeller University in New York, New York.
The group's task is to create an "encyclopedia" of innate
immunitya comprehensive and detailed picture of this
ancient, essential first line of defense against bacterial
and fungal diseases that is mustered by humans, fruit flies,
and all creatures in between.
"There are lots of questions we would like to ask about
gene expression and protein expression in innate immunity,"
says TSRI Professor and Chair of Immunology Richard J. Ulevitch,
the project's principal investigator. "But to accomplish this
in the broadest terms we need to define gene and protein expression
patterns when the innate immune system is triggered by invading
The funds will go towards discovering new ways to study
the immune system in living tissue in real time and to provide
materials and information to the scientific community at large.
Knowledge generated could help scientists develop treatments
for septic shock, certain autoimmune disorders, and diseases
caused by potential agents of bioterrorism.
A Systems Approach to Innate Immunity
Innate immunity is essential for survival in a world filled
with microbial pathogens. Cells of the innate immune system
are the body's first responders, arriving soon after foreign
elements are detected. Some innate cells find and engulf microorganisms,
while others release chemicals that kill the organism directly.
Still other cells begin recruiting other specialized immune
components to the region.
Severe defects in the innate immune system make humans highly
susceptible to normally benign infections, which can then
become life threatening. For instance, babies born without
functional neutrophilsone of the primary cell types
of the innate immune systemdo not live more than a few
days due to the effects of infection.
While the adaptive immune system, which forms the other
half of the human immune system, has been studied since the
dawn of immunology, it is only in the last few years that
researchers have begun to understand the innate immune system
in detail, Ulevitch says. The innate immune system has turned
out to be much more complex than anybody had imagined.
Ulevitch and his co-investigators face a daunting taskidentifying
the thousands of tiny molecular and biochemical changes that
are triggered by encounters between innate immune system cells
and infectious agents. Unlike the highly specific antibodies
of the adaptive immune response, 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 bacteria.
The grant investigators aim to identify and study the key
players of innate immunity on both sides of the battle. Investigators
are interested in the bacterial and fungal "ligands"the
molecules found in the cell walls of bacteria and other substances
that are recognized by innate immune cells, as well as the
"receptor" molecules on the immune cells that recognize the
ligands. A multiplicity of different ligands are recognized
by 10 or more different receptors in the innate immune system.
The investigators are also interested in discovering the "signal
transduction" pathways through which this immune recognition
triggers the innate immune response.
The researchers will take a "systems biology" approach to
identifying all these players. Dubbed "21st-century biology,"
the relatively new field of systems biology melds mathematics,
computer modeling, and the new techniques of genomics and
proteomics in an effort to gain a wide-angle view of biological
In contrast to traditional hypothesis-driven research, in
which a single gene or protein is selected for study based
on its proposed function, the TSRI, ISB, and Rockefeller University
approach will assemble information about multiple genes, proteins,
and biochemical reactions without regard for function. The
idea is that this data can then be integrated and examined
from multiple perspectives to learn how the system as a whole
behavesinformation that will later form the basis for
A large portion of the funding will be dedicated to setting
up certain shared core facilities at TSRI and ISB that will
centralize and enhance some of the tasks common to the dozens
of researchers with independently funded research projects
at the institutions. The grant will help generate information
and materials for the research community at large by funding
a large database with free data access. Bi-monthly video conferences
will bring participating scientists together on a regular
"[We aim] to leverage the existing expertise in biology
and high-throughput technology platforms at these institutions,"
says Ulevitch. "We appreciate the NIAID's vision in funding
the huge project. Individual grants can only address individual
questionswe are throwing out a huge net, and this would
not be possible without the support of the NIAID."