biomedical nanotechnology might help shed light on
the molecular mechanisms responsible for one of the
U.S.'s deadliest diseases.
The National Heart, Lung, and Blood Institute (NHLBI), National Institutes
of Health (NIH), has awarded researchers from Georgia Institute of Technology
and Emory University $11.5 million to establish a new research program focused
on creating advanced nanotechnologies to analyze plaque formation on the molecular
level and detect plaque at its early stages. Plaques containing cholesterol
and lipids may build up during the life of blood vessels. When these plaques
become unstable and rupture they can block the vessels, leading to heart attack
The multi-disciplinary program, part of NHLBI's Program of Excellence in Nanotechnology
(PEN), is headed by Dr. Gang Bao, a professor in the Wallace H. Coulter Department
of Biomedical Engineering at Georgia Tech and Emory University. The program
includes 12 faculty investigators from both institutions and will be based
at Emory. It is one of four national PEN awards. The initiative is in accord
with the NIH Roadmap's strategy to accelerate progress in medical research
through innovative technology and interdisciplinary research.
The program's work will focus primarily on detecting plaque and pinpointing
its genetic causes with three types of nanostructured probes – molecular beacons,
semiconductor quantum dots and magnetic nanoparticles.
Healthy, undamaged cells lining the vessel wall do not attract platelets or
cause a build-up of plaque. But in a diseased blood vessel, cells lining the
vessel wall may have certain cellular and molecular characteristics that make
them stickier, causing platelets to stick to the vessel wall, create plaque
blockage and obstruct blood flow.
A molecular beacon is a biosensor about four to five nanometers in size that
can seek out and detect specific target genes. It is a short piece of single-stranded
DNA (ssDNA) in the shape of a hairpin loop with a fluorescent dye molecule
at one end and a “quencher” molecule at the other end. The ssDNA is synthesized
to match a region on a specific messenger RNA (mRNA) that is unique to the
gene. The fluorescence of the beacon is quenched, or suppressed, until it seeks
out and binds to a complementary target mRNA, which causes the hairpin to open
up and the beacon to emit light.
The level of gene expression within a cell can reflect susceptibility to disease.
The fluorescence from the beacons will vary with the level of the target genes'
expression in each cell, creating a glowing marker if the cell has a detectable
level of gene expression that is known to contribute to cardiovascular disease.
“With molecular beacons, we hope to follow the dynamics of gene expression in
normal and diseased cells,” Bao said. “We can find out how quickly these genes
are being turned on and how the expression levels are correlated with factors
contributing to early plaque formation.”
To complement gene expression studies using molecular beacons, the team will
develop quantum-dot nanocrystal probes and use them to study protein molecular
signatures of cardiovascular disease. Quantum dots are nanometer-sized semiconductor
particles that have unique electronic and optical properties due to their size
and their highly compact structure. Quantum dot based probes can act as markers
for specific proteins and cells and can be used to study protein-protein interactions
in live cells or to detect diseased cells. These ultra-sensitive probes may
help cardiologists understand the formation of early stage plaques and dramatically
improve detection sensitivity.
Other research will include using magnetic nanoparticles to detect early-stage
plaques in patients. The magnetic nanoparticles will target specific proteins
on the surface of cells in a plaque, and serve as a contrast agent in magnetic
resonance imaging (MRI). This could provide an image of the plaque formation
and could become a powerful tool for better disease diagnosis. The investigators
will also develop ultra-sensitive probes for the free radicals inside cells
and biomolecular constructs for molecular imaging and therapeutics.
The program will integrate the biomedical engineering strengths of Georgia
Tech and the cardiology expertise of Emory University School of Medicine. The
new program is part of the joint Wallace H. Coulter Department of Biomedical
Engineering at Georgia Tech and Emory, established in 1997, and currently
ranked third in the nation by U.S. News & World Report.
In addition to this cardiovascular nanotechnology award and an ongoing cancer
nanotechnology program, the Georgia Tech/Emory group also plans to expand biomolecular
engineering and nanotechnology to the detection and treatment of other diseases,
such as neurodegenerative and infectious diseases.
“This program is only part of a larger scale biomedical nanotechnology effort
at Georgia Tech and Emory,” said Dr. Larry McIntire, The Wallace H. Coulter Chair
in the Department of Biomedical Engineering at Georgia Tech and Emory. “We are
pleased to add cardiology to our growing breadth of nanomedicine research.”
“The synergistic research relationship between Emory and Georgia Tech in engineering
and medicine demonstrates the power of discovery that becomes possible when two
institutions join their unique yet complementary strengths in an entirely new
scientific approach to solving complex problems of medicine,” said Dr. James
W. Wagner, president of Emory University.
“The Programs of Excellence in Nanotechnology is a vitally important research
effort that will spur the development of novel technologies to diagnose and treat
heart, lung, and blood diseases,” said Elizabeth G. Nabel, MD, director of the
National Heart, Lung, and Blood Institute. “The program brings together bioengineers,
materials scientists, biologists and physicians who will work in interdisciplinary
teams. By taking advantage of the unique properties of materials at the nano-scale,
these teams will devise creative
solutions to medical problems.”
Co-investigators on the project include Emory cardiologists Wayne Alexander,
MD, PhD, Kathy Griendling, PhD, David Harrison, MD, Charles Searles and Robert
Taylor, MD; and biomedical engineers from Georgia Tech and Emory Don Giddens,
PhD, Xiaoping Hu, PhD, Hanjoong Jo, PhD, Niren Murthy, PhD, Shuming Nie, PhD
and Dongmei Wang, PhD.
The Georgia Institute of Technology is one of
the nation's premiere research universities. Ranked
among U.S. News & World Report 's top 10 public
universities, Georgia Tech educates more than 16,000
students every year through its Colleges of Architecture,
Computing, Engineering, Liberal Arts, Management
and Sciences. Tech maintains a diverse campus and
is among the nation's top producers of women and
African-American engineers. The Institute offers
research opportunities to both undergraduate and
graduate students and is home to more than 100
interdisciplinary units plus the Georgia Tech Research
Institute. During the 2003-2004 academic year,
Georgia Tech reached $341.9 million in new research