Joint research projects aim to lay foundation for new medical treatments,
diagnostics
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ARGONNE, Ill. (Feb. 27, 2007) — Better treatment for infections, breast
and prostate cancer, and certain brain injuries, as well as improved detection
developing tumors, are the focus of new joint research by the U.S. Department
of Energy's Argonne National Laboratory and the University of Chicago.
The programs are funded through the Seed Fund Program of the Research Advisory
Committee of the university's Division
of Biological Sciences and Argonne National Laboratory.
Revolutionary changes in approaches and technologies are highlighting the
need for multidisciplinary efforts in biomedical science. Consequently, funding
agencies are focusing a greater proportion of their research investments on
team science that employs novel tactics, technologies and collaborations. In
light of these changes, the Research Advisory Committee's goal is to increase
the university's competitiveness for these types of interdisciplinary funding
opportunities.
One way the committee is doing this is through the seed fund program, which
provides pilot funding to interdisciplinary teams of researchers from the university's
division of Biological Sciences and Physical Sciences and Argonne. Projects
funded through this program are expected to form the basis of subsequent proposals
submitted to external funding agencies.
New projects funded by the Seed Fund Program are:
Development of bio-conjugated nanoparticle reagents for breast/prostate
cancer imaging and therapy: Researchers will develop metal and metal-oxide
nanoparticles conjugated to estradiol or to a suitable androgen, which will
specifically target membrane estrogen and androgen receptors.
Using a metal or metal-oxide particle core, conjugated nanoparticles that
bind to cell surface receptors offer the possibility of elucidating and exploiting
nongenomic actions of estrogens and androgens in cancer cells. By tuning the
particle size while maintaining the surface chemistry, it may also be possible
to achieve specific binding of metal particles and clusters to either the cell
surface or the cell nucleus, which offers the opportunity to selectively control
the nongenomic, as well as genomic, actions of steroid-conjugated particles.
Specific targeting of these bio-conjugated nanoparticle reagents will open
new possibilities for imaging as well as therapies based on radiation enhancement
effects of nanoparticles.
Principal investigators on this project are Geoffrey Greene of the University
of Chicago and Xiao-Min Lin of Argonne.
MgrA, a new target for the treatment of Staphylococcus aureus infection: Staphylococcus
aureus, a gram-positive bacterium, is the leading cause of a variety
of human infections ranging from minor skin infection to life-threatening
endocarditis, pneumonia and septicemia. Researchers have identified the protein
MgrA as a key global regulator in S. aureus. This protein controls
expression of a wide variety of virulence factors, autolysis and other global
regulatory genes. In addition, MgrA also regulates resistance to quinolone
type antibiotics and glycopeptide resistance.
A preliminary study of MgrA resulted in a recent major breakthrough. Researchers
have solved a high resolution structure of MgrA and revealed a unique oxidation
regulation mechanism of this protein. A small molecular inhibitor of MgrA was
also discovered. The next step is to elucidate structure, function and mechanism
of MgrA, and to develop small molecule inhibitors and activators for MgrA.
Principal investigators are the University of Chicago's Chuan He, Olaf Schneewind,
Phoebe A. Rice, Peng Chen and Zigang Li.
Imaging polymer-mediated repair of the neuronal plasma membrane at the
nanoscale level: Acute hypoxic-ischemic brain injury is an important
cause of long-term neurologic morbidity in babies, children and adults without
treatment. Poloxamer 188 (P188), a tri-block copolymer surfactant of polyethylene-polypropylene-polyethylene,
has been shown to rescue cultured hippocampal neurons from multiple in
vitro models of hypoxia-ischemia. Exciting preliminary data indicate
marked neuroprotection by P188 in a gerbil model of transient forebrain ischemia.
P188 has also been shown to rescue neurons through interactions with neuronal
plasma membranes.
Rescuing injured neurons by repairing the plasma membrane, therefore, is a
novel approach to neuroprotection and may lead to a new class of compounds
for the treatment of hypoxic-ischemic brain injury. The goal of the application
is to devise an experimental approach and to obtain pilot data of low- to medium-resolution
imaging of tri-block copolymer interactions with the plasma membrane of living
hippocampal neurons.
Principal investigators are Jeremy Marks of the University of Chicago and
Argonne's Millicent Firestone.
Phase-enhancement micro-computed tomography: Researchers will develop
and streamline phase-enhancement micro-computed tomography (PRMCT) and its
potential application to imaging, quantitatively characterizing and monitoring
tumor angiogenesis, a process by which tissue develops new capillaries from
an existing microvascular network.
Specifically, the goals are to develop and streamline volumetric PEMCT for
targeted imaging of region of interest, to develop novel algorithms for accurately
reconstructing PEMCT images for the acquired data and to evaluate the performance
of the proposed PEMCT and algorithms.
Principal investigators are the University of Chicago's Xiaochuan Pan and
Francesco De Carlo of Argonne.
Argonne National Laboratory brings
the world's brightest scientists and engineers together to find exciting and
creative new solutions to pressing national problems in science and technology.
The nation's first national laboratory, Argonne conducts leading-edge basic
and applied scientific research in virtually every scientific discipline. Argonne
researchers work closely with researchers from hundreds of companies, universities,
and federal, state and municipal agencies to help them solve their specific
problems, advance America 's scientific leadership and prepare the nation for
a better future. With employees from more than 60 nations, Argonne is managed
by UChicago
Argonne, LLC for
the U.S.
Department of Energy's Office
of Science.
For more information, please contact Catherine Foster (630-252-5580 or cfoster@anl.gov)
at Argonne or John Eastman
(773-702-6241 or John.Easton@uchospitals.edu)
at the University of Chicago Hospitals.
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