The National Science Foundation (NSF) has awarded $3 million to the Georgia Institute of Technology to fund a unique research program on stem cell bio-manufacturing. The program is specifically focused on developing engineering methods for stem cell production, in order to meet the anticipated demand for stem cells. The award comes through the NSF's Integrative Graduate Education and Research Traineeship (IGERT) Program, which supports innovation in graduate education in fields that cross academic disciplines and have broad societal impact.

While stem cell research is on the verge of broadly impacting many elements of the medical field - regenerative medicine, drug discovery and development, cell-based diagnostics and cancer - the bio-process engineering that will be required to manufacture sufficient quantities of functional stem cells for these diagnostic and therapeutic purposes has not been rigorously explored.

"Successfully integrating knowledge of stem cell biology with bioprocess engineering and process development into single individuals is the challenging goal of this program," said Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and a Petit Faculty Fellow in the Parker H. Petit Institute for Bioengineering and Biosciences at Georgia Tech.

McDevitt is leading the IGERT with Robert M. Nerem, professor emeritus of the George W. Woodruff School of Mechanical Engineering at Georgia Tech. Nerem is also director of the Georgia Tech/Emory Center (GTEC) for Regenerative Medicine, which will administer this award.

Ph.D. students funded by Georgia Tech's stem cell bio-manufacturing IGERT will receive interdisciplinary educational training in the biology, engineering, enabling technologies, commercialization and public policy related to stem cells. Their research efforts will focus on developing innovative engineering approaches to bridge the gap between basic discoveries made in stem cell biology and therapeutic stem cell-based technologies.

"This program provides a unique opportunity for engineers to generate standardized and quantitative methods for stem cell isolation, characterization, propagation and differentiation," said Nerem. "These techniques must be developed in a scalable manner to efficiently produce sufficient numbers of stem cells and derivatives in accessible formats in order to yield a spectrum of novel therapeutic and diagnostic applications of stem cells."

The Georgia Tech program is centered around three main research thrusts, which focus on several critical technologies that must be developed to enable the application and use of stem cell-based products:

* Creating reproducible, controlled and scalable methods to expand and differentiate stem cells with defined phenotypes and epigenetic states.
* Developing reliable, rapid and quantifiable methods to characterize the composition and function of stem cells to be generated.
* Designing low-cost systems capable of producing large populations of defined stem cells and derivatives.

Students in the program will be able to take advantage of the core facilities provided by the new Stem Cell Engineering Center at Georgia Tech, which is directed by McDevitt. Technologies developed by the students supported through this IGERT will be rapidly integrated into academic and industrial stem cell practices and cell-based products.

The award will support 30 new Ph.D. students over the next five years and brings together more than two dozen faculty members from Georgia Tech, Emory University, the University of Georgia and the Morehouse School of Medicine. In addition, plans are being made for students to participate in international research collaborations with the National University of Ireland at Galway, Imperial College London, the University of Cambridge and the University of Toronto.

"We anticipate this program will produce the future leaders and innovators in the field of stem cell bio-manufacturing who will contribute significantly at the interface of stem cell engineering, biology and therapy," added McDevitt.

Scientists at the Georgia Institute of Technology have attained very promising results on their initial investigations of a new test for ovarian cancer. Using a new technique involving mass spectrometry of a single drop of blood serum, the test correctly identified women with ovarian cancer in 100 percent of the patients tested. The results can be found online in the journal Cancer Epidemiology, Biomarkers, & Prevention Research.

"Because ovarian cancer is a disease of relatively low prevalence, it's essential that tests for it be extremely accurate. We believe we may have developed such a test," said John McDonald, chief research scientist at the Ovarian Cancer Institute (Atlanta) and professor of biology at Georgia Tech.

The measurement step in the test, developed by the research group of Facundo Fernandez, associate professor in the School of Chemistry and Biochemistry at Tech, uses a single drop of blood serum, which is vaporized by hot helium plasma. As the molecules from the serum become electrically charged, a mass spectrometer is used to measure their relative abundance. The test looks at the small molecules involved in metabolism that are in the serum, known as metabolites. Machine learning techniques developed by Alex Gray, assistant professor in the College of Computing and the Center for the Study of Systems Biology, were then used to sort the sets of metabolites that were found in cancerous plasma from the ones found in healthy samples. Then, McDonald's lab mapped the results between the metabolites found in both sets of tissue to discover the biological meaning of these metabolic changes.

The assay did extremely well in initial tests involving 94 subjects. In addition to being able to generate results using only a drop of blood serum, the test proved to be 100 percent accurate in distinguishing sera from women with ovarian cancer from normal controls. In addition it registered neither a single false positive nor a false negative

The group is currently in the midst of conducting the next set of assays, this time with 500 patients.

"The caveat is we don't currently have 500 patients with the same type of ovarian cancer, so we're going to look at other types of ovarian cancer," said Fernandez. "It's possible that there are also signatures for other cancers, not just ovarian, so we're also going to be using the same approach to look at other types of cancers. We'll be working with collaborators in Atlanta and elsewhere."

In addition to having a relatively low prevalence ovarian cancer is also asymptomatic in the early stages. Therefore, if further testing confirms the ability to accurately detect ovarian cancer by analyzing metabolites in the serum of women, doctors will be able detect the disease early and save many lives.

Researchers engaged in studying the origins of life celebrated a new $20 million grant from the National Science Foundation and the National Aeronautics and Space Administration yesterday at a gala presided over by Provost Gary Schuster. Researchers will focus their efforts on exploring chemical processes that enable the spontaneous formation of functional polymers -- such as proteins and DNA -- from much smaller and simpler starting materials.

"Our research team seeks to understand how certain molecules in a complex mixture can work together to form highly ordered assemblies that exhibit chemical properties similar to those associated with biological molecules," said Nicholas V. Hud, a professor in the Georgia Tech School of Chemistry and Biochemistry. "Such a process was likely an essential and early stage of life, so we are also working to understand what chemicals were present on the prebiotic Earth and what processes helped these chemicals form the complex substances ultimately needed for life."

Hud will direct the effort, which is known as the Center for Chemical Evolution. The five-year grant will support research in more than 15 laboratories at institutions including Georgia Tech, Emory University, the Scripps Research Institute, the Scripps Institution of Oceanography, Jackson State University, Spelman College, Furman University and the SETI Institute.

All of the researchers will work together to accomplish the Center for Chemical Evolution's three main research goals:

To identify potential biological building blocks among the products of model prebiotic reactions,to investigate the chemical components and conditions that promote the spontaneous assembly of increasingly complex multi-component structures, and to prepare and characterize highly-ordered chemical assemblies, and to study their potential to function like biological substances.
Representatives from some of the partner institutions and the National Science Foundation (NSF) were on hand to mark the occasion with remarks and a ribbon cutting.

"The Georgia Research Alliance is proud to have at least two of our universities, Georgia Tech and Emory, collaborating with others on this project," said Susan Shows, senior vice president of the Georgia Research Alliance. "There are many groundbreaking programs under way on our campuses - more than my company can support in many cases. So when federal agencies put competitive funding into a program, it makes it easy for the GRA to know where to invest its strategic dollars."

Other speakers included: Charles Liotta, interim chair of the School of Chemistry and Biochemistry at Georgia Tech; Pat Marsteller, director of the Emory College Center for Science Education at Emory University; Loren Williams, director of Tech's NASA Ribosome Center; Katherine Covert, NSF program director for Integrative Chemistry Activities; and Matthew Platz, incoming director of the NSF Division of Chemistry.

A team of institutions led by the Georgia Institute of Technology has been awarded a $20 million grant from the National Science Foundation and the National Aeronautics and Space Administration to pursue research that could lead to a better understanding of how life started on Earth. Researchers will focus their efforts on exploring chemical processes that enable the spontaneous formation of functional polymers — such as proteins and DNA - from much smaller and simpler starting materials.

"Our research team seeks to understand how certain molecules in a complex mixture can work together to form highly ordered assemblies that exhibit chemical properties similar to those associated with biological molecules," said Nicholas V. Hud, a professor in the Georgia Tech School of Chemistry and Biochemistry. "Such a process was likely an essential and early stage of life, so we are also working to understand what chemicals were present on the prebiotic Earth and what processes helped these chemicals form the complex substances ultimately needed for life."

Hud will direct the effort, which is known as the Center for Chemical Evolution. The five-year grant will support research in more than 15 laboratories at institutions including Georgia Tech, Emory University, the Scripps Research Institute, the Scripps Institution of Oceanography, Jackson State University, Spelman College, Furman University and the SETI Institute.

All of the researchers will work together to accomplish the Center for Chemical Evolution’s three main research goals:

* To identify potential biological building blocks among the products of model prebiotic reactions,
* To investigate the chemical components and conditions that promote the spontaneous assembly of increasingly complex multi-component structures, and
* To prepare and characterize highly-ordered chemical assemblies, and to study their potential to function like biological substances.

"We will work backward from the complex substances found in living organisms today, such as proteins and DNA, and make materials that are a little bit different and simpler in chemical structure," explained Hud. "We will then strive to determine if there were possibly chemicals and conditions on the early Earth that would have given rise to these and similar substances."

In addition, the researchers will translate technological developments into commercially viable products. Facundo Fernandez, an associate professor in the Georgia Tech School of Chemistry and Biochemistry, is leading the Center's commercialization efforts.

For the first research theme, which is being led by Georgia Tech chemistry professor Thomas Orlando, creating a model inventory of the chemicals present on the early Earth will require the development of new tools and approaches for analyzing and sorting complex mixtures.

"Complex mixtures are found in many chemical industries - including petroleum, food and pharmaceuticals," said Fernandez. "The instruments and protocols we develop to sort through the complex mixtures that result from model prebiotic chemical reactions are going to be valuable to these industries too."

Charles Liotta, a Regents professor in the Georgia Tech School of Chemistry and Biochemistry, is leading the second research theme, which involves exploring alternative media that could have facilitated the assembly of complex substances in the prebiotic world. This research could produce environmentally-friendly procedures leading to new chemical processes, according to the team.

In the third research theme, led by David Lynn, chair of the Department of Chemistry at Emory University, and Ram Krishnamurthy, an associate professor of chemistry at the Scripps Research Institute, methods will be developed to create polymers and assemblies that mimic natural macromolecules, such as DNA and proteins. The resulting methods could be used as a platform to create a range of substances with broad commercial applications across the spectrum of therapeutics, diagnostics and drug delivery materials. Lynn will also lead the Center's education and public outreach programs.

The research efforts of the Center will build on the knowledge and results gained during the past three years, during which time a smaller group of laboratories were funded by the National Science Foundation to conduct collaborative research projects and to develop a larger center.

Research progress made during the initial phase of funding includes a paper published June 14 in the journal ChemBioChem. Center laboratories showed for the first time that guanine, a component of DNA, could be produced from formamide (H2NCOH), a simple chemical known to exist in outer space.

Previous research had shown that the other three building blocks of nucleic acids - cytosine, adenine and uracil - could be synthesized by heating formamide in the presence of mineral catalysts, but not guanine.

Center researchers produced guanine from formamide by subjecting the sample to ultraviolet light during the heating process. The results also demonstrated that guanine, adenine and another building block called hypoxanthine could be produced at lower temperatures than previously reported.

"Our ultimate goal is to create a complete chemical pathway showing how relatively simple substances can interact with the environment and each other to spontaneously produce complex assemblies that exhibit properties normally associated with biological substances, and perhaps shed some light on the earliest stages of life on Earth," noted Hud.

Ravi Bellamkonda, a professor in the Wallace H. Coulter Department of Biomedical Engineering, has been named an associate vice president within the Office of the Executive Vice President for Research (EVPR). The three-year appointment, which begins on August 1, enables Bellamkonda to divide his time evenly between his own research and the administrative responsibilities of this new position.

In announcing the appointment, Executive Vice President for Research Steve Cross said, "I worked closely with Ravi during the strategic planning process of the past year and was pleased to learn of his continued interest in supporting Georgia Tech research on an institutional level. Ravi is a first-rate scientist with excellent intellectual curiosity and temperament, and I am excited about his joining our leadership team."

A Georgia Cancer Coalition Distinguished Scholar, Bellamkonda directs the Neurological Biomaterials and Cancer Therapeutics Laboratory and a National Institutes of Health (NIH) T32 training program in the Rational Design of Biomaterials. He also served as deputy director for research at the Georgia Tech & Emory Center for Regenerative Medicine (GTEC).

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A new animal model of atherosclerosis has allowed researchers to identify a host of genes turned on or off during the initial stages of the process, before a plaque appears in the affected blood vessel.

The model is the first to definitively show that disturbances in the patterns of blood flow in an artery determine where atherosclerosis will later appear, says senior author Hanjoong Jo, PhD, Ada Lee and Pete Correll professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

The first author of the paper is Chih-Wen Ni, a graduate student in biomedical engineering.

Atherosclerosis describes a process where the arterial walls thicken and harden, because of a gradual build-up of white blood cells, lipids and cholesterol. This process can lead to plaque formation, and eventually to heart attacks and strokes.

Jo says his team's results could provide insight into how aerobic exercise, known to provide protection against atherosclerosis, improves the patterns of blood flow and encourages protective genes to turn on in blood vessels.

Scientists have previously observed that atherosclerosis occurs preferentially in branched or curved regions of arteries, because of the "disturbed flow" branches and curves create. Constant, regular flow of blood appears to promote healthy blood vessels, while low or erratic flow can lead to disease.

The standard laboratory model of atherosclerosis has scientists feeding a high-fat diet to mice with mutations in a gene (ApoE) involved in removing fat and cholesterol from the blood. Even then, atherosclerosis usually takes a few months to develop. In these models, clogs in a mouse's arteries tend to appear in certain places, such as the aortic arch, but flow patterns are set up at birth and thus are poor gauges of cause and effect, Jo says.

"We have developed a model where we disturb blood flow in the carotid artery by partial ligation, and atherosclerosis appears within two weeks," he says. "This rapid progression allows us to demonstrate cause and effect, and to examine the landmark events at the beginning of the process."

Jo says that endothelial cells, which form the inner lining of blood vessels, are equipped with sensors that detect changes in fluid flow.

"Disturbed flow is what causes the endothelial cells to become inflamed," he says.

The inflammation resulting from "bad flow" conditions in a stretch of artery causes white blood cells to accumulate there, followed by buildup of cholesterol and lipids and plaque formation.

Just 48 hours after blood flow in the carotid arteries was disturbed, Ni and colleagues dissected the carotid arteries from the mice and used genome-wide microarray technology to identify hundreds of genes that were turned on or off in the endothelial cells.

In past experiments, scientists grew endothelial cells in dishes to probe how different patterns of fluid flow affected their patterns of genes. However, growing cells in dishes alters them enough that many of the genes Jo's team found have not been identified before in this context.

For example, the team showed that the gene LMO4 - not previously known to be involved in atherosclerosis - is turned on in their mouse model and also in human coronary arteries. Scientists studying breast cancer think LMO4 is involved in tumor migration and invasion, making an interesting parallel between atherosclerosis and cancer, Jo says.

He says his laboratory is now probing which of the newly identified genes are most important in atherosclerosis and searching for ways to manipulate them with drugs or genetic techniques, with an eye towards possible diagnostic and pharmaceutical applications.

The research was supported by the National Heart, Lung and Blood Institute, the Ada Lee and Pete Correll Professorship at Emory and Georgia Tech, and the World Class University project at Ewha Womans University in South Korea.

The results were published June 15 in Blood, the journal of the American Society of Hematology.

IBB Industrial Partners Program has created a new YouTube video detailing its mission and importance in the biotechnology community.

This video is complete with interviews of industry partners, faculty, students and staff, explaining the history of the program and their roles as it relates to the necessity of these collaborations.

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