Category: research

Expanding the fight against Infectious Diseases

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CEIGD.pngThe UGA Faculty of Infectious Diseases is comprised of many Franklin College faculty members and departments, researchers who have garnered significant resources in the fight against a variety of global health challenges:

"The board of regents investment in infectious disease research provided a unique opportunity to recruit strategically to bridge existing strengths in veterinary medicine, ecology, tropical and emerging diseases, and vaccine development as well as the rapidly expanding the new College of Public Health at UGA," said Duncan Krause, director of UGA's Faculty of Infectious Diseases and a professor of microbiology in the Franklin College of Arts and Sciences. "The resulting synergy has been exceptional."

Their studies promise to continue to enhance the research enterprise at UGA and foster new partnerships, both within the UGA Faculty of Infectious Diseases, which brings together researchers across UGA colleges and schools, and with researchers globally.

"A particular strength of the faculty members recruited through the board of regents initiative is their ability to identify promising collaborative opportunities that enable new research capabilities and often spawn new research directions," Krause said.

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Don Harn and Biao He study very different infectious agents, but both expand UGA capabilities in vaccine development. A major research focus of the Harn lab is schistosomiasis, a disease caused by worm-like organisms found in water. This work builds upon UGA's global leadership efforts to control this disease, including the Gates Foundation SCORE program here under the direction of Dan Colley. Harn's research also explores how schistosomiasis can limit the effectiveness of vaccines against HIV and other viral diseases.

He has identified a virus with potential as a delivery vector for vaccines and gene therapy. This discovery has spawned multiple new collaborations with researchers at UGA and beyond.

Having met an Infectious Diseases researcher from another Franklin department earlier today, I can vouch for this program's broad reach across our campus. The nature of fighting emerging and established global diseases dictates an interdisciplinary mix of specialties plus an ability to synthesize voluminous amounts of data even as they expand on it. Data management and sharing is an emerging challeneg itself for scientists and researchers in the digital age, one will revisit soon.

 

Genetics researchers unveil fully functional lab-grown thymus

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Manley_Nancy-portrait.jpgA major advance from researchers in the department of genetics:

A team of scientists including researchers from the University of Georgia have grown a fully functional organ from scratch in a living animal for the first time.

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The researchers created a thymus, a butterfly-shaped gland and vital component of the human immune system. Located beneath the breastbone in the upper chest, the thymus is responsible for producing T-lymphocytes, or T-cells, which help organize and lead the body’s fighting forces against threats like bacteria, viruses and even cancerous cells.

“We were all surprised by how well this works,” said Nancy Manley, professor of genetics in UGA’s Franklin College of Arts and Sciences and co-author of the paper describing their finding in Nature Cell Biology.

“The general idea in science is that to make cells change their fate, you need to reprogram first to a stem-cell like state and then coax them to change into what you want,” said Manley, who is also director of UGA’s Developmental Biology Alliance. “But we jump-started the process just by expressing a single gene that was sufficient to initiate the entire process and orchestrate organ development.”

Congratulations to the research team on this fantastic news, a very big step along the way to clinical trials and treatments which, while they might be still far out in the future, seem to have just become significantly closer.

Nature article highlights UGA malaria researcher

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R_cellbio2012_01.jpgCongratulations are in order to University of Georgia professor Vasant Muralidharan, an assistant  professor in the Franklin College of Arts and Sciences department of cellular biology. His research was recently highlighted in the journal Nature.  Muralidharan, who studies the biology of the deadly malaria eukaryotic parasite, worked with with a group of researchers as a post-doc at Washington University School of Medicine in St. Louis to investigate a means to trap and kill the parasite. You can read more and hear an accompanying audio piece about this published research here

Scientists may be able to entomb the malaria parasite in a prison of its own making, researchers at Washington University School of Medicine in St. Louis report July 16 in Nature.

As it invades a red blood cell, the malaria parasite takes part of the host cell’s membrane to build a protective compartment. To grow properly, steal nourishment and dump waste, the parasite then starts a series of major renovations that transform the red blood cell into a suitable home.

But the new research reveals the proteins that make these renovations must pass through a single pore in the parasite’s compartment to get into the red blood cell. When the scientists disrupted passage through that pore in cell cultures, the parasite stopped growing and died.

Muralidharan now works on his research here at UGA and his work is a great addition to the collaborative efforts of researchers at the Center for Tropical and Emerging Global Diseases. His lab website describes the crux of his research interests as follows:

New research tracks Amazon River microbial activity, effects on global carbon budget

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Amazon-River-Plume.jpg

New research from the University of Georgia Franklin College of Arts and Sciences  departments of microbiology and marine sciences could have a major impact on the study of microbial activity in the Amazon River, as well as the effects on the global carbon budget.. The Amazon River, the largest in the world in terms of discharge water, transfers a plume of nutrients and organisms into the ocean that creates a hotspot of microbial activity.  This affects many global processes, including the storage of atmospheric carbon.

The new study further reveals detail about the microbial activity of the Amazon River Plume as part of a broad project to understand the global carbon budget and its possible impacts on a changing ocean. The study, "Microspatial gene expression patterns in the Amazon River Plume," was published July 14 in the online edition of the Proceedings of the National Academy of Sciences.

"By collecting data from genes and gene transcripts in the water samples, taking billions of sequences of DNA and RNA from organisms at various places in the plume, we were able to construct the most detailed look that's ever been put together of the microbial processes in a drop of seawater," said Mary Ann Moran, Distinguished Research Professor of Marine Sciences at UGA.

UGA researchers from the Franklin College of Arts and Sciences departments of marine sciences and microbiology took samples from the plume 300 miles offshore from the Amazon River mouth, then isolated the genes of organisms using the nutrients, nitrogen, phosphorus and carbon being carried into the ocean by the river plume.

Discharge from the plume, more than 200,000 cubic meters of fresh water per second, delivers nitrogen and phosphorus to microscopic phytoplankton that live in the upper sunlit layers of the ocean. Via photosynthesis, phytoplankton capture carbon dioxide that dissolves into the ocean from the atmosphere, a mechanism that captures a larger proportion of CO2 than is consumed by the world's rainforests.

Until now, quantitative data about the microbial activity underlying this mechanism has been elusive.

Data in the paper will used be as part of a larger model of the Amazon and will be available to researchers around the world.

"The scientific community as a whole can draw new conclusions or study different aspects from the data sets," said Brandon Satinsky, a doctoral student in microbiology at UGA and lead author on the study. "It's such a large amount of water and material, and the location of the plume moves over the course of the year, from the Caribbean virtually over to Africa."

"It's first time we've had this kind of data, at this level of detail, and so now we can share with teams of modelers to help them make better predictions about the future of the system," Moran said.

The project is part of two major UGA research initiatives: ROCA, the River Continuum of the Amazon; and ANACONDAS, Amazon iNfluence on the Atlantic: CarbOn export from Nitrogen fixation by DiAtom Symbioses, both of which are led by associate professor of marine sciences Patricia Yager. The initiatives are supported by the Gordon and Betty Moore Foundation through grant GBMF2293 and the National Science Foundation.

For more on UGA research in the Amazon, see http://amazoncontinuum.org/.

New nanoparticle treatment for stroke victims

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nano-biocleanroom zhaoGreat new work from Franklin College researchers that should garner significant attention:

Researchers at the University of Georgia and their collaborators have developed a new technique to enhance stroke treatment that uses magnetically controlled nanomotors to rapidly transport a clot-busting drug to potentially life-threatening blockages in blood vessels.

The only drug currently approved for the treatment of acute stroke—recombinant tissue plasminogen activator, or t-PA—is administered intravenously to patients after the first symptoms of ischemic stroke appear. The protein in the drug dissolves blood clots that cause strokes and other cardiovascular problems, like pulmonary embolisms and heart attacks.

"Our technology uses magnetic nanorods that, when injected into the bloodstream and activated with rotating magnets, act like stirring bars to drive t-PA to the site of the clot," said Yiping Zhao, co-author of a paper describing the results in ACS Nano and professor of physics in UGA's Franklin College of Arts and Sciences. "Our preliminary results show that the breakdown of clots can be enhanced up to twofold compared to treatment with t-PA alone."

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Stroke is the second leading cause of death worldwide, according to the World Health Organization, while the Centers for Disease Control and Prevention estimates that one American dies from stroke every four minutes.

"We're dealing with a huge population of patients who desperately need new treatments," said Leidong Mao, paper co-author and associate professor in UGA's College of Engineering.

Medical advances can sometime appear quite far removed from the source of their greatest need - either only focused on a small aspect of a condition or only remotely connected to a future treatment regime. Zhao, Mao and their colleagues have a special intuition about getting to the essence of a problem, drug delivery in this instance, and forging solutions with the use of technology developed in their labs. Congratulations to this team of perceptive researchers as they seek to utilize technology to improve the efficiency of the t-PA drug to help stroke and heart attack victims.

Image: Professor Yiping Zhao

Chemistry researchers enhance chemotherapy with nanoparticles

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Dhar_Marrache_Pathak.jpgAs science moves forward, disease treatment regimes become more refined, safer and more effective. Great news from Shanta Dhar's research lab in the department of chemistry:

Dhar, assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and Rakesh Pathak, a postdoctoral researcher in Dhar's lab, constructed a modified version of cisplatin called Platin-M, which is designed to overcome this resistance by attacking mitochondria within cancerous cells. They published their findings recently in the Proceedings of the National Academy of Sciences.

"You can think of mitochondria as a kind of powerhouse for the cell, generating the energy it needs to grow and reproduce," said Dhar, a member of the UGA Cancer Center and principal investigator for the project. "This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive."

Sean Marrache, a graduate student in Dhar's lab, entrapped Platin-M in a specially designed nanoparticle 1,000 times finer than a human hair that seeks out the mitochondria and releases the drug. Once inside, Platin-M interferes with the mitochondria's DNA, triggering cell death.

Dhar's research team tested Platin-M on neuroblastoma-a cancer commonly diagnosed in children-that typically originates in the adrenal glands. In preliminary experiments using a cisplatin-resistant cell culture, Platin-M nanoparticles were 17 times more active than cisplatin alone.

Improving on current therapies can be a very difficult target. But with an expanding knowledge about the role of mitochondria in cell survival, drug design and delivery mechanism on the nanoscale have scientists poised for promising breakthroughs. Great work.

Image: Shanta Dhar (center), Rakesh Pathak (right) and Sean Marrache, courtesy of UGA Photographic Services.

Chemistry doctoral graduate Gilliard awarded Merck Fellowship

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R_Gilliard.gif2014 doctoral graduate in the department of chemistry Robert J. Gilliard, Jr., has been awarded a UNCF/Merck Foundation Postdoctoral Science Research Fellowship. The award provides $92,000 and includes a stipend, research grant and travel funds for up to two years of fellowship tenure:

Gilliard will pursue research projects focused on synthetic chemistry and will collaborate with John Protasiewicz of Case Western Reserve University in Cleveland, Ohio, and Hansjörg Grützmacher of ETH Zürich—an engineering, science, technology, mathematics and management university in Zürich, Switzerland. Gilliard will depart for Zürich in August.

"This is a tremendous honor for which I am extremely grateful," said Gilliard, a native of Hartsville, South Carolina, who came to UGA in 2009 to work with Gregory H. Robinson, the Foundation Distinguished Professor of Chemistry. "My experience at UGA has been highly rewarding in research as well as teaching, and I'm looking forward to these new opportunities for collaboration."

Gilliard is one of UGA's best, who chose to come to the university to work with our best faculty. In Gilliard's case, that meant Foundation Distinguished Professor of Chemistry Gregory H. Robinson. said Robinson of Gilliard:

"Robert arrived at UGA with a clear career plan, and he has worked hard to realize his ambition, forging new directions in the synthetic organic chemistry of beryllium."

An extraordinarily bright young researcher and teacher, Gilliard has already achieved great, early career distinction and we look for more in the future. Congratulations to Gilliard and to the department of chemistry on this prestigious fellowship.

The Impact of Giving

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Scholarship and research support from private giving to the Franklin College avails our students and faculty of broad opportunities across every aspect of society. This short video, featuring a student and one of our donors, elaborates on the impact of giving:

 

 

 

New genetics research: direct conversion of biomass

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Transporting_Miscanthus_BalesMore potentially transformative new research from the department of genetics, this time in the realm of transportation fuels. For sometime now, biofuels have held great promise - and have been the focus of great controversy. But the economics of the conversion process of grasses to fuels may have finally seen its last barrier fall:

Pre-treatment of the biomass feedstock—non-food crops such as switchgrass and miscanthus—is the step of breaking down plant cell walls before fermentation into ethanol. This pre-treatment step has long been the economic bottleneck hindering fuel production from lignocellulosic biomass feedstocks.

Janet Westpheling, a professor in the Franklin College of Arts and Sciences department of genetics, and her team of researchers—all members of U.S. Department of Energy-funded BioEnergy Science Center in which UGA is a key partner—succeeded in genetically engineering the organism C. bescii to deconstruct un-pretreated plant biomass.

"Given a choice between teaching an organism how to deconstruct biomass or teaching it how to make ethanol, the more difficult part is deconstructing biomass," said Westpheling, who spent two and a half years developing genetic methods for manipulating the C. bescii bacterium to make the current work possible.

The UGA research group engineered a synthetic pathway into the organism, introducing genes from other anaerobic bacterium that produce ethanol, and constructed a pathway in the organism to produce ethanol directly.

"Now, without any pretreatment, we can simply take switchgrass, grind it up, add a low-cost, minimal salts medium and get ethanol out the other end," Westpheling said. "This is the first step toward an industrial process that is economically feasible."

Emphasis mine. With no pre-treatment and the ability of microbe to transform the feedstock into ethanol (and other, higher-energy-yield fuels), this process is ready for industrial scale up. Westpheling explained how biofuels are already the standard in Brazil. Is the U.S. on the verge of a transformative fuel moment?

Image: Bales of miscanthus being transported in the U.K., courtesy of Wikimedia Commons. Miscanthus and switchgrass are the best biofuel feedstock because of the high tons-per-acre yield.

Study deepens the connection between hypoxia and cancer growth

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There are a number of species that have a low to negligible probability of developing cancer. These include squirrels, turtles, the mole rat and certain whales. The reasons why are linked to these species' ability to adapt their oxygen demand when faced with a low oxygen supply. That connection itself goes back to a discover by the great physiologist and Nobel laureate Otto Warburg, who hypothesized in 1924 that, whatever the secondary causes of cancer, there is only one primary cause: a cell switch to fermentation of sugars in the face of low oxygen levels. The details of this fascinating story have now been filled in a little further by UGA bioinformatics and computational bioloy professor, Regents-GRA Eminent Scholar Ying Xu:

Chronic inflammation that induces low oxygen levels, or hypoxia, is a widely accepted cause of cancer development. However, the link between hypoxia and cell proliferation is far from clear.

A new study by University of Georgia researchers presents a model explaining the connection between chronic inflammation, low oxygen levels and the resulting cell proliferation that begins the cancer process.

"A switch in energy metabolism mechanisms—from the normal oxygenic respiration our cells use to process glucose into energy to a much less efficient, much lower capacity process called anaerobic fermentation—leads to glucose accumulation," said Ying Xu, a Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the UGA Franklin College of Arts and Sciences.

According to the study, this accumulation of glucose and related signaling through the body leads to a reaction much the same as to that of damaged tissue, eventually triggering the cell proliferation that causes cancer. Specifically it leads to synthesis, export and fragmentation of hyaluronic acids, which can serve as signals for tissue repair.

A fascinating and important breakthrough, in a field reluctant to use that term but where many desperately hope for its reality. Building on the work of the past, questioning current practices, explaining a complex process through the use of simple analogs - all the hallmarks of great research. The idea that cancer cell growth might be understood as a survival reaction, to a mistaken circumstance, in the body could not have wider significance. Great work and there's no doubt more to come from Xu and his team.