CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 384-4638
Release: Feb. 25, 2002
UI and University of Hawaii researchers receive $2 million from the W.
M. Keck Foundation
A luminous squid and a chronic lung infection in a person with cystic fibrosis
(CF) may not seem to have much in common. However, both are examples of persistent
infection of an animal host by a bacterium. Scientists at the University of
Iowa and the University of Hawaii plan to study the parallels between these
The investigation will be funded by a three-year, $2 million grant to the
UI Foundation from the W. M. Keck Foundation and will draw on the unique expertise
of researchers at the UI College of Medicine and the Kewalo Marine Laboratory
at the Pacific Biomedical Research Center (PBRC) of the University of Hawaii.
Studying chronic infections in animals is difficult over the long term because
the animals usually either beat the infections and recover, or succumb and
die. However, University of Hawaii research on the lifelong infection of bobtail
squid by a light-emitting bacterium (Vibrio fischeri) has resulted in an experimentally
useful model of chronic infection. This model will be combined with the UI
expertise in bacterial biofilms and the disease process of CF.
"There are many parallels between chronic infections in humans and the
symbiotic relationship between the bobtail squid and this light-emitting bacterium,"
said E. Peter Greenberg, Ph.D., the Virgil L. and Evalyn Sheppard Professor
of Molecular Pathogenesis and UI professor of microbiology. "The principles
of engagement, as far as we can tell, seem to be the same. We just don't know
what they all are."
Many persistent infections are caused by biofilms, organized groups of bacteria
encased in a self-produced matrix. At the UI, Greenberg and his colleagues
have shown that the bacterium Pseudomonas aeruginosa forms biofilms in the
lungs of individuals with CF. These biofilms are highly resistant to antibiotics
and cause an overactive inflammatory response by the CF patient's immune system.
The researchers hope that an improved understanding of persistent bacterial
infection of animal hosts will lead to the development of drugs to treat chronic
infection and inflammation in humans.
The W. M. Keck Foundation is one of the nation's leading philanthropic organizations.
It funds pioneering research efforts designed to open up new fields of investigation
and lead to breakthrough discoveries and the development of new technologies.
"The W. M. Keck Foundation grant allows us to put together a program
that we couldn't otherwise do with the type of funding usually available even
to well-funded senior faculty," Greenberg said. "It allows us to
try all sorts of novel things."
UI President Mary Sue Coleman and University of Hawaii President Evan S.
Dobelle played key roles in developing this request to the W. M. Keck Foundation.
Coleman presented the proposal to the W. M. Keck Foundation.
"President Dobelle and I are excited about the interdisciplinary research
and collaboration between our institutions made possible by this grant from
the W. M. Keck Foundation," Coleman said. Dobelle stated the grant "will
advance one of the most strategically important priorities of the University
of Hawaii -- expanding research in the biomedical sciences."
A first step in the study will be to sequence the genome of the light-emitting
Vibrio fischeri bacterium. This information will be used to construct a DNA
microarray, or gene chip, containing DNA fragments representing the bacterium's
genes. The researchers will collaborate with Integrated Genomics, a Chicago-based
research firm, to build the microarray.
Greenberg and his colleagues have already used microarrays of Pseudomonas
genes to investigate this bacterium as it exists as a biofilm. However, Greenberg
explained that it can be difficult to obtain funding to make microarrays for
bacteria like V. fischeri, which don't cause human diseases.
"This microarray is exactly the tool we need to draw these parallel
between Pseudomonas and Vibrio fischeri," Greenberg said.
The team also plans to construct a microarray of genes from the squid. These
various microarrays will be used to investigate the molecular and genetic
interactions of the two host-bacteria pairings.
Greenberg's earlier work showed that chemical communication, or signaling,
between individual bacterial cells is a critical step in biofilm development.
The researchers believe that cell-to-cell signaling between a bacterium and
its host also is important and complex.
"The host is detecting the bacteria and responding, and the bacteria
are detecting each other and responding, and detecting the host cells and
responding," Greenberg said. Fellow investigator Margaret McFall-Ngai,
Ph.D., professor of biology, Hawaii, described it as a "whole dialogue
"We want to understand the dialogue because every step is a possible
point of intervention for treatment of chronic infections," Greenberg
A second project in the investigation also stems from an unusual combination
of expertise between researchers at the UI and Hawaii. Michael Apicella, M.D.,
UI professor and head of microbiology, is an expert on how particular bacterial
cell-surface molecules trigger inflammation in humans. Together, the researchers
in Hawaii and Apicella have discovered that the same surface molecules on
the Vibrio bacteria also trigger a reaction in the squid, but in the symbiotic
relationship, the reaction is not harmful.
"Somehow, the bacteria in the squid's light organ are limiting inflammation,"
Greenberg said. "That's a good trick because despite the chronic infection,
the host cells are being told not to be alarmed."
Understanding how this trick works might lead to ways of limiting or preventing
the harmful inflammation that often accompanies chronic infection in humans.
Using the squid model, the team will study the interaction of the host cells
with the bacteria cell surface signaling molecules.
Finally, Greenberg and his colleagues are interested in pursuing indications
of other kinds of group behavior in bacteria. Potentially, these studies could
uncover new types of cell-to-cell signaling between bacteria.
"The Keck grant gives us the opportunity to pursue these novel lines
of investigation and we are the ideal group to do it because of our combined
expertise," Greenberg said. "We plan to open up new areas of research."
In addition to Greenberg and Apicella, the principal scientists at the UI
include Michael J. Welsh, M.D., the Roy J. Carver Chair in Physiology and
Biophysics, professor of internal medicine and physiology and biophysics,
and a Howard Hughes Medical Institute Investigator; and Timothy L. Yahr, Ph.D.,
assistant professor of microbiology.
At the University of Hawaii, the investigation's principal scientists are
Edward G. Ruby, Ph.D., professor of bacteriology, and Margaret McFall-Ngai,
Ph.D., professor of biology. The University of Hawaii Web site can be found
The W. M. Keck Foundation grant is part of a planned comprehensive campaign
to advance the UI's strategic goals for the years 2000-2005. The campaign
is in its early stages and no final dollar goal has been established. It will
be conducted under the guidance of the UI Foundation and will raise funds
to substantially increase the number of UI scholarships and endowed faculty
chairs and professorships; to fund outreach and service programs to benefit
individuals, families and communities throughout the state of Iowa; to support
new educational and research facilities; to build the UI's endowment; and
to launch new initiatives in the arts, sciences, business, health care and
other fields. The UI Foundation is the preferred channel for private contributions
to all areas of the University of Iowa.
University of Iowa Health Care describes the partnership between the
UI College of Medicine and the UI Hospitals and Clinics and the patient care,
medical education and research programs and services they provide. Visit UI
Health Care online at www.uihealthcare.com.