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A five-member team of researchers led by Xiaohong Nancy Xu, associate professor of chemistry and biochemistry at Old Dominion University, has accomplished a feat in a nanobiotechnology project funding that would be called an upset in the sports arena.

Competing against more established and better equipped research centers at some of the nation's most prestigious universities, the ODU-based team won a $1.3 million award in June from the National Science Foundation to perform fundamental studies in nanobiotechnology. The field brings together chemistry, biology and engineering practiced on a scale so tiny as to be hard to imagine.

Two other ODU faculty members are co-principal investigators for the grant, Christopher Osgood, associate professor of biological sciences, and Hani Elsayed-Ali, eminent scholar and professor of electrical and computer engineering. Richard Van Duyne, professor of chemistry and materials science at Northwestern University, and Daniel Gillet, a French scientist who specializes in protein engineering, are also co-principal investigators.

The NSF award is part of a national initiative in nanoscience and nanotechnology, and comes under the specific category of grants to Nanoscale Interdisciplinary Research Teams (NIRT). Xu and her colleagues titled their project, "NIRT: Design of Biocompatible Nanoparticles for Probing Living Cellular Functions and Their Potential Environmental Impacts."

For the next four years, the team will expand upon recent studies of nanoparticles and single living cells by Xu's research group in biochemistry at ODU, which includes seven doctoral students. The NSF project will tackle questions that must be answered before theorized nanoscience breakthroughs can become realities in fields such as medicine.

"The award recognizes what we have accomplished so far and shows that the NSF believes ODU has the scientists and engineers and facilities to support the work," Xu said. "This award also demonstrates the power of teamwork and collaboration. I am very pleased and grateful for the support of my research group and co-PIs."

ODU Provost Thomas Isenhour, who is a chemist, said the research "is truly at the frontier of the interface of chemistry and biological science." By focusing on the transport of nanomaterials across membranes in living cells, the team will be making important contributions to science at the nanoscale, he said.

Others at ODU who offered guidance and support for the NSF application, she said, include Kenneth Brown, chair of the Chemistry and Biochemistry Department; Lytton Musselman, Mary Payne Hogan professor of botany and chair of the Biological Sciences Department; Richard Gregory, dean of the College of Sciences; Joseph Rule, associate dean of the college; Oktay Baysal, dean of the College of Engineering; Philip Langlais, dean of graduate studies, and Mohammad Karim, vice president for research.

Karim said the university's research initiative encourages convergence of people, equipment and ideas from differing fields. "This is an example of an interdisciplinary research project that draws faculty members from both sciences and engineering, and has the potential to affect the design of biologically inspired smart pumps and sensors." Added Langlais: "This project provides important financial support and a cutting-edge multidisciplinary research environment needed to train our doctoral students and prepare future leaders in this rapidly growing area of bioscience."

Gregory applauded Xu's "dedication to science and innovative thinking." He said Osgood and Elsayed-Ali bring impressive research credentials to the project and that the "award is well-deserved."

Reports in popular media during recent years have predicted mind-boggling advances in materials, electronics and medicine from nanotechnology. ("Nano" means billionth, so a nanometer is one-billionth of a meter and a nanosecond is one-billionth of a second. Work at the nanoscale involves measurements and manipulation done upon individual molecules and cells.)

In one possible application, a nanoparticle would be loaded with a miniscule dose of a potent anti-cancer drug. The nanoparticle would target and penetrate a tumor cell in order to deliver a precise amount of the drug directly into the cell. The tumor cell would be destroyed without the potent drug harming any normal tissue.

But much research remains to be done before this becomes a reality, and it is with fundamentals of nanobiotechnology that the Xu team has excelled.

For example, Xu and Van Duyne have in recent years achieved exceptional results with their production of nanoparticles. These nanoparticles are "characterized" by shapes and properties necessary to facilitate research into cell membrane transport and intra-cellular probes. To accomplish this grading of the nanoparticles, Elsayed-Ali will be using his special skills with transmission electron microscopy and atomic force microscopy.

"You have to have the nanoparticles," Osgood explained. "You can't go out and buy desired ones." Under the grant, team members will further develop the single nanoparticle optics that allows scientists to track cellular function using nanoparticle probes.

The Xu research group has designed and constructed state-of-the-art imaging systems and accomplished real-time monitoring of nanoparticles in and out of living cells using various types of microscopy. Xu said the keys to the success of the grant included the assemblage of a well-qualified team and her research group's pioneering work in single nanoparticle optics for real-time, living cell imaging. In 2004 alone, she and her group published five research papers on this work. "Without the publication record and the interdisciplinary team, this grant would never have been possible," she said.

Her research group also has demonstrated results involving cell functions that provide a foundation for another phase of the grant research. Proteins in a cell can assemble to bring about an efflux pump process that transports harmful molecules out of the cell. Xu said a particularly fascinating portion of the NSF project will focus on efflux pump. "No human is able to make such a smart pump that can recognize and extrude harmful particles. How does the pump do this?" Xu, Osgood and Gillet will further study the function of the pump using single nanoparticle optics.

The pump is of particular interest in medicine because "harmful" molecules that are expelled sometimes are antibiotics and other disease-fighting agents prescribed by a physician to kill cells. The efflux pump of the bacteria cell can expel so much antibiotic that the drug either does not work as intended, or has to be prescribed in an amount that can be toxic to healthy tissue. This team of researchers will conduct extensive research with nanoparticle probes to expand understanding of the efflux pump mechanism.

Other research to be funded by the grant will assess damage that nanoparticles may do to cells or to genes. In addition, there are environmental concerns involving the disposal of nanoparticles that the research will touch upon.

Finally, there will be an educational aspect to the project. The three ODU researchers will develop and co-teach an interdisciplinary special-topic course, Frontiers in Nanoscience and Nanotechnology, for seniors and graduate students. They also will give a presentation, "Impact of Nanomaterials on Our Environment," for the New Portals to Appreciating our Global Environment (NewPAGE), a compulsory freshman course. An annual public-lecture exchange will bring Gillet and Van Duyne to ODU and put at least one American researcher on the team before an audience at the Natural History Museum in Paris.

Xu and Osgood said they hope the grant paves the way for a larger commitment to nanotechnology by ODU, the region and the state.

"I hope we can establish a stronger base of nano facilities and a team of researchers in nanoscience and nanotech," Xu said. "Then we will be able to go after larger awards for nanoscience and engineering centers, perhaps in two to three years."

"This (NSF award) is a first step," Osgood said. "We have a brief window to get into this field with both feet, to find a niche, because the nano field is wide open now and has potential to impact every aspect of sciences and engineering. If we wait any longer, we will lose the opportunity to lead. We are glad to have such a great opportunity to participate and compete."

Xu received her bachelor and master's degrees in physical chemistry from Xiamen University in China and received a doctoral degree in chemistry from the University of Mississippi in 1992. She did postdoctoral work at the University of Texas at Austin and Ames Laboratory-DOE at Iowa State University before coming to ODU six years ago. She has quickly established a reputation in nanobiotechnology that takes her to conferences and seminars worldwide. She sits on the review panels in nanoscience and nanotechnology for the National Institutes of Health, Environmental Protection Agency and NSF. In August she will present research at a nanomedicine conference at Johns Hopkins University in Baltimore and at a four-day American Chemical Society symposium in Washington, D.C., concerning single molecule detection and single-cell analysis. Xu organized and will chair the ACS symposium.

This article was posted on: August 8, 2005

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