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Author: Donna Huber

Building on big data, UPenn and UGA awarded $23.4 million pathogen genomics database contract

Jessica Kissinger

Athens, Ga. – A genome database team led by University of Pennsylvania and University of Georgia scientists has been awarded a new contract from the National Institutes of Allergy and Infectious Disease worth $4.3 million in 2014-2015. Assuming annual renewal, this five-year award is expected to total $23.4 million.

The team has been responsible for developing genome database resources for microbial pathogens, including the parasites responsible for malaria, sleeping sickness, toxoplasmosis and many other important diseases.

The new contract ensures work will continue on the Eukaryotic Pathogen Genomics Database—known as EuPathDB—to provide the global scientific community with free access to a wealth of genomic data related to microbial pathogens important to human health and biosecurity. EuPathDB expedites biomedical research in the lab, field and clinic, enabling the development of innovative diagnostics, therapies and vaccines.

Each month, EuPathDB receives over 6.5 million hits from 13,000 unique visitors in more than 100 countries, including areas where tropical diseases such as malaria are endemic. India is now the second largest user of its plasmodium genome database, and over 5 percent of users hail from Africa. The overall project employs 28 people on four continents.

EuPathDB is jointly directed by principal investigators David S. Roos, the E. Otis Kendall Professor of Biology in Penn’s School of Arts and Sciences, and Jessica C. Kissinger, professor of genetics and director of the UGA Institute of Bioinformatics. Christian Stoeckert of Penn’s Perelman School of Medicine is a co-investigator.

One of four pathogen bioinformatics resource centers supported by the National Institutes of Health, EuPathDB is responsible for disease-causing eukaryotes, which are organisms that possess a membrane-bound nucleus. Other centers support data on viruses, bacteria and insect vectors of disease.

“This database has expedited research in many ways,” said Kissinger, a member of the UGA Center for Tropical and Emerging Global Diseases. “Vaccine scientists frequently want to examine how proteins have changed over time to identify those with signatures indicating that they provoke the human immune system. Those studying a specific antigen may wish to examine its structure and diversity in order to prioritize those regions that might be most promising and relatively unlikely to develop resistance.”

Since its prototype was launched in 1999, the EuPathDB family of databases has become increasingly complex and increasingly valuable as a resource for researchers around the world. In total, the databases comprise about 9 terabytes of data and have been cited more than 8,000 times in the scientific literature.

“The costs and time required for genome sequencing have plummeted in the past 10 years thanks to advances in technology,” Kissinger said. “Organizing this data, maintaining it in a way that is accessible and easy to use for researchers around the world, 24 hours a day, is our great challenge-and one that presents exciting opportunities for funders and other philanthropic organizations that support pathogen research.”

The latest contract is the third time that NIH has awarded support to EuPathDB, building on previous contracts issued in 2004 and 2009 as well as prior grant funding from the NIH and the Burroughs Wellcome Fund. Affiliated projects have also been supported by the Wellcome Trust, the Bill and Melinda Gates Foundation, the Sloan Foundation, the World Health Organization, the U.S. Department of Agriculture, the Brazilian government and other organizations.

“The sophistication of the questions people can ask continues to increase,” Roos said in a press release from UPenn. “As we move to the next phase of this project, our job is to ensure that this resource remains dynamic, taking into account how people interact with the data in ways that can have a real impact on global health.”

Writer: Alan Flurry
Contact:Jessica Kissinger

UGA, Emory collaborate to leverage strengths in infectious disease research

Jessica Kissinger

Athens, Ga. – The University of Georgia and Emory University are strengthening their collaborations to elevate the position of the Atlanta-Athens corridor as a national hub for infectious disease research.

The two institutions are currently working together on grant and contract-funded projects totaling more than $45 million, including a Center of Excellence for Influenza Research and Surveillance and a malaria research consortium, both funded by the National Institutes of Health (NIH). In addition, they are developing a new diagnostic test for tuberculosis and working to create a new HIV vaccine, among other projects.

These partnerships and others like them will be enhanced by a series of ongoing meetings among senior administrators initiated by the institution’s two presidents, Jere W. Morehead of UGA and James Wagner of Emory, shortly after Morehead came into office.

“The combined research strengths of our two institutions, particularly in infectious diseases, create a formidable effort to develop better methods of prevention, detection and treatment for some of the most challenging global health challenges,” said Wagner.

“These collaborations reflect the complementary strengths of two of Georgia’s leading research universities and our shared commitment to conducting globally significant research,” said Morehead. “By working together, we are advancing the state’s economically important bioscience sector while laying the foundation for improvements in health and quality of life around the world.”

Earlier this year, the Emory-UGA Center of Excellence for Influenza Research and Surveillance (CEIRS) received a $3.6 million contract-with potential funding up to $26.7 million over seven years-from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH. The Emory-UGA CEIRS, originally launched and funded in 2007, is one of five national centers that integrate research to lessen the impact of epidemic influenza and improve pandemic influenza preparedness.

The Emory-UGA CEIRS is led by Dr. Walter Orenstein, professor of medicine and associate director of the Emory Vaccine Center. Researchers at Emory are studying how flu viruses cause infection and spread in the population, the human immune response to flu vaccines, flu infection in pregnancy and the response to flu vaccines in pregnant women. Under the leadership of Ralph Tripp, Georgia Research Alliance Chair in Vaccine and Therapeutic Development at UGA, the center has established an extensive surveillance network to identify flu viruses in swine that could potentially become human pandemic strains and is evaluating the immune response to flu viruses and vaccines. In addition, the researchers are collaborating with colleagues in China to monitor flu viruses that infect swine and poultry.

“Through merging the research expertise of our two institutions, our influenza center is a key component of the national effort to prepare for and help prevent emerging influenza outbreaks, including seasonal flu and pandemic strains,” said Orenstein.

Emory, UGA and Georgia Tech also are collaborating within a malaria research consortium funded by a five-year contract of up to $19.4 million from the NIAID. Scientists in the Malaria Host-Pathogen Interaction Center (MaHPIC), led by Dr. Mary Galinski from the Emory School of Medicine and Yerkes National Primate Research Center, are building a “molecular encyclopedia” cataloguing how malaria parasites interact with their human and animal hosts. New mathematical models are helping analyze the details of an infection and identifying patterns that predict the course of the disease and its severity.

“New tests from our effort could help us screen for dormant parasites and identify biomarkers to predict which cases will become the most severe, potentially leading to drug discovery and a malaria vaccine,” said Galinski.

UGA professor of genetics Jessica Kissinger, who directs the UGA Institute of Bioinformatics, is leading a team that is organizing, distributing and mining the massive quantities of data produced by the project with the ultimate goal of identifying new opportunities to diagnose the disease, which causes an estimated 660,000 deaths annually.

“The goal of my team is to integrate the terabytes of data being produced on both the host and the parasite and make it accessible to our mathematical modelers, who are looking for patterns and signals, as well as the global malaria research community to guarantee that this large investment has the biggest impact possible on malaria research,” Kissinger said.

In addition to flu and malaria, UGA and Emory researchers are making strides against tuberculosis, which kills an estimated 1.5 million people worldwide each year. A team of scientists from the two institutions recently developed the first rapid diagnostic test to identify latent tuberculosis, the most common form of the disease. Latent tuberculosis doesn’t cause symptoms in people who are otherwise healthy, but it can develop into dangerous and potentially deadly tuberculosis in late-stage AIDS patients and other vulnerable populations.

The diagnostic test-developed by UGA Athletic Association Professor of Infectious Diseases Fred Quinn and Dr. Henry M. Blumberg, professor of medicine in the division of infectious diseases at the Emory School of Medicine-measures the concentration of proteins that are only present if the bacteria that cause tuberculosis are replicating. With $1 million in funding from the Food and Drug Administration, the researchers completed a small but promising preliminary study and are now wrapping up a larger study to verify the effectiveness of the diagnostic method.

“The current tests cannot identify latent disease, which may account for 60 to 90 percent of the potential two billion cases worldwide,” said Quinn, a faculty member in the UGA College of Veterinary Medicine. “With an accurate diagnosis of latent tuberculosis, patients-particularly those with compromised immune systems-can receive potentially lifesaving treatment.”

In a project funded by a five-year, $2.8 million NIH grant, Emory and UGA researchers are developing an HIV vaccine that induces the immune system to attack the virus before it can spread through the body. The vaccine uses a virus known as PIV5, which causes kennel cough in dogs but doesn’t cause symptoms in humans, and virus-like particles that mimic the HIV virus. This one-two punch vaccine approach could stimulate immune responses in areas of the body where the virus is known to first infect cells, therefore preventing further spread.

“In the past 30 years of HIV vaccine research, we have learned a lot about how to generate immune responses that might protect people from infection. However, we don’t yet have a vaccine that we know for certain will protect individuals from HIV,” said Emory Professor of Pediatrics and Microbiology Dr. Paul Spearman, who is collaborating with Biao He, the Davison Distinguished University Chair in Veterinary Medicine at UGA.

“I am delighted to be working with Dr. He, the world’s expert in the use of PIV5 as a vaccine. Together we are optimistic that this prime-boost vaccine approach will generate immune responses to combat the virus in mucosal sites such as the gut. If successful, this will prevent the very early phase of HIV spread and could protect against HIV infection and AIDS.”

Writer: Sam Fahmy
Writer: Holly Korschun

UGA researchers discover route for potential Chagas disease animal vaccine

Rick Tarleton

Athens, Ga. – Researchers at the University of Georgia have discovered a new way to direct a vaccine to the parasite that causes Chagas disease, a leading cause of death among young to middle-age adults in areas of South America where it is endemic.

Chagas disease is caused by the parasite Trypanosoma cruzi, which spreads via a subspecies of blood-feeding insects commonly known as “kissing bugs” because they tend to bite people on the face and lips. While the disease can progress slowly, chronic infection almost inevitably results in irreparable damage to heart and digestive system tissues.

“Chagas disease is incredibly understudied, because it is a disease of poverty,” said Rick Tarleton, Distinguished Research Professor in the department of cellular biology in UGA’s Franklin College of Arts and Sciences and co-author of a paper describing their work in Cell Host and Microbe. “I don’t know if we will ever see a Chagas disease vaccine for humans, but our lab is working on a unique vaccine for animals that may ultimately protect people at greatest risk for exposure.”

The paper reported a new vaccine technique that targets antibodies found on T. cruzi’s flagellum, a tail-like appendage similar to those found on sperm cells, which allows the parasite to propel itself through blood as it searches for cells to infect.

Immediately after infection, the flagellum essentially snaps off through a process of cell division. The discarded tail is broken down by the host cell, but it leaves behind a kind of molecular calling card that Tarleton and his co-author, Samarchith Kurup, were able to isolate and use as the foundation for a vaccine.

In laboratory tests, T cells taught to recognize the proteins found on the flagellum were able to detect infected host cells more than 20 hours earlier than is normally observed, suggesting that the immune system became aware of the parasite’s presence very shortly after infection.

“We want to find a way to help the animal’s immune system recognize which cells are infected with the parasite, and the antigens in the flagellum are an attractive target,” Tarleton said. “If we can express these proteins in a vaccine, T cells will go to work and destroy compromised cells before the infection becomes chronic.”

A significant portion of Tarleton’s work in UGA’s Center for Tropical and Emerging Global Diseases has focused on the development of a vaccine that can be administered to domestic animals, which play a major role in Chagas disease transmission throughout much of the Americas.

“The bugs that transmit this disease are found commonly in substandard housing with poor insulation, but the bugs tend to acquire the parasite from the family pet that spends a lot of time outside,” he said. “These are the same bugs that go on to bite people, so if we can prevent animals from acquiring the disease, we can hopefully prevent T. cruzi’s spread into human populations.”

The research team hopes that this latest discovery will become a major component of its vaccine development, which will ultimately target multiple unique signatures created by T. cruzi infection.

“There’s a lot more work to do, but this new target will be very helpful in the fight against Chagas’ disease,” Tarleton said.

For a full version of the paper, see

The research discussed in this article was supported by two grants from the National Institutes of Health under project numbers AI108265 and AI108265.

Writer: James Hataway
Contact:Rick Tarleton