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.”

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.”

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.”

An international team of scientists comprised of more than 200 researchers from 80 institutions from 20 countries has sequenced and analyzed the genomes of 48 species of birds and 3 species of crocodilians to better understand the fundamental evolutionary events that led to feathers, flight, and song. The Avian Phylogenomics Consortium is simultaneously publishing 28 papers today — eight papers in a special December 12 issue of Science and 20 more in Genome Biology, GigaScience and other journals. The University of Georgia’s Associate Professor of Environmental Health Science (EHS) Travis Glenn co-authors two of the papers in Science , Assistant Professor Liang Liu of the Institute of Bioinformatics (IOB) and Department of Statistics, and Toxicology PhD student John Finger Jr. each coauthor one paper in Science. UGA alumni authors of the papers in Science include: Brant Faircloth (PhD, Forestry & Natural Resources), Richard E. Green (B.S., Genetics), Daniel Peterson (PhD, Plant Biology), and Beth Shapiro (B.S., Genetics).

 

One of the flagship papers in Science reports the relationships of major groups of birds. This is one of the most challenging problems in evolutionary biology because these groups diverged in a very short period of time, quite a long time ago – about 66 million years ago, shortly after dinosaurs became extinct. The Avian Phylogenomics Consortium used the new genome sequences and developed new laboratory and computational methods developed by Liu and Glenn to tackle this problem.

 

Liu has developed computational methods to analyze DNA sequences to understand relationships among species. These methods provide more robust results than traditional approaches. These methods are to key to solving the puzzle about relationships among birds because they are designed to overcome the problems associated with short bursts of speciation, even when they happened long ago. Liu and Glenn have collaborated previously to make these methods available to public health workers and evolutionary biologists (http://bioinformatics.publichealth.uga.edu/).

 

A new genomic tool that Glenn and colleagues developed for this research uses ultraconserved elements (UCEs), which consist of short DNA sequences that are nearly identical in birds, reptiles, and humans. Glenn says, “Brant Faircloth and I developed UCEs to address a variety of questions. In the avian phylogenome paper, we have used UCEs to understand how different birds are related to each other, making it easier to make apples to apples comparisons of DNA sequences among all birds as well as their distant relatives.”

 

In the crocodilian genome paper published in Science, Glenn and colleagues also used UCEs to compare the rate of molecular evolution of all major groups of tetrapods (vertebrates with 4 limbs) – ranging from the coelacanth to amphibians, birds, reptiles and mammals, including humans. By directly comparing DNA fragments that started with identical DNA sequences hundreds of millions of years ago, and yet still contain short stretches that are nearly identical today, the team discovered that crocodilians have remarkably slow rates of molecular evolution compared to other tetrapods. Turtles were the only other group with similarly slow rates of evolution. They also use UCEs and other parts of the genome to show the impact of glacial cycles on the population size of alligators, as well as reconstructing the genome of the ancestor of birds, crocodiles, and dinosaurs.

 

“The crocodilian genome paper is the culmination of more than 20 years of work developing genetic and genomic tools for alligators and crocodiles. UGA has supported this research through training of students, who are now among the lead authors and co-authors on these papers, hosting sponsored research on alligators and crocodiles, as well as providing international travel support and faculty research enhancement support for alligator genome resources when I was a research scientist at the Savannah River Ecology Laboratory (SREL)”, said Glenn.

 

John Finger, Jr., a PhD student in the Interdisciplinary Toxicology Program (ITP) and EHS worked with Glenn and colleagues at SREL and Australia to obtain alligator and saltwater crocodile samples used in the project. “Being a co-author on a publication in Science is a great graduation gift”, said Finger, who will graduate next week. “I want to thank the ITP as well as my mentors in EHS, SREL, and Veterinary Medicine, for giving me the opportunity to conduct research on alligators in the USA and saltwater crocodiles in Australia.” Finger is returning to Australia following graduation to continue research on crocodiles.

 

“This research provides the foundation for further work to understand how diseases, such as avian flu, and the effects of environmental toxicants, such as heavy metals, can be shared between humans, birds, reptiles, and other animals”, said Glenn. “Many additional faculty and students at UGA, especially those at SREL, EHS, IOB and the ITP, have contributed to this body of work. I wish there were space to recognize and thank them all for their support, but that would be an extremely long list. I look forward to working with even more colleagues at UGA to use these new resources and new genomic tools to continue research that improves human and environmental health“ added Glenn.

 

Links:

 

https://www.publichealth.uga.edu/ehs/

http://bioinformatics.publichealth.uga.edu/SpeciesTreeAnalysis/index.php

An international team of scientists comprised of more than 200 researchers from 80 institutions from 20 countries has sequenced and analyzed the genomes of 48 species of birds and 3 species of crocodilians to better understand the fundamental evolutionary events that led to feathers, flight, and song. The Avian Phylogenomics Consortium is simultaneously publishing 28 papers today — eight papers in a special December 12 issue of Science and 20 more in Genome Biology, GigaScience and other journals. The University of Georgia’s Associate Professor of Environmental Health Science (EHS) Travis Glenn co-authors two of the papers in Science , Assistant Professor Liang Liu of the Institute of Bioinformatics (IOB) and Department of Statistics, and Toxicology PhD student John Finger Jr. each coauthor one paper in Science. UGA alumni authors of the papers in Science include: Brant Faircloth (PhD, Forestry & Natural Resources), Richard E. Green (B.S., Genetics), Daniel Peterson (PhD, Plant Biology), and Beth Shapiro (B.S., Genetics).

 

One of the flagship papers in Science reports the relationships of major groups of birds. This is one of the most challenging problems in evolutionary biology because these groups diverged in a very short period of time, quite a long time ago – about 66 million years ago, shortly after dinosaurs became extinct. The Avian Phylogenomics Consortium used the new genome sequences and developed new laboratory and computational methods developed by Liu and Glenn to tackle this problem.

 

Liu has developed computational methods to analyze DNA sequences to understand relationships among species. These methods provide more robust results than traditional approaches. These methods are to key to solving the puzzle about relationships among birds because they are designed to overcome the problems associated with short bursts of speciation, even when they happened long ago. Liu and Glenn have collaborated previously to make these methods available to public health workers and evolutionary biologists (http://bioinformatics.publichealth.uga.edu/).

 

A new genomic tool that Glenn and colleagues developed for this research uses ultraconserved elements (UCEs), which consist of short DNA sequences that are nearly identical in birds, reptiles, and humans. Glenn says, “Brant Faircloth and I developed UCEs to address a variety of questions. In the avian phylogenome paper, we have used UCEs to understand how different birds are related to each other, making it easier to make apples to apples comparisons of DNA sequences among all birds as well as their distant relatives.”

 

In the crocodilian genome paper published in Science, Glenn and colleagues also used UCEs to compare the rate of molecular evolution of all major groups of tetrapods (vertebrates with 4 limbs) – ranging from the coelacanth to amphibians, birds, reptiles and mammals, including humans. By directly comparing DNA fragments that started with identical DNA sequences hundreds of millions of years ago, and yet still contain short stretches that are nearly identical today, the team discovered that crocodilians have remarkably slow rates of molecular evolution compared to other tetrapods. Turtles were the only other group with similarly slow rates of evolution. They also use UCEs and other parts of the genome to show the impact of glacial cycles on the population size of alligators, as well as reconstructing the genome of the ancestor of birds, crocodiles, and dinosaurs.

 

“The crocodilian genome paper is the culmination of more than 20 years of work developing genetic and genomic tools for alligators and crocodiles. UGA has supported this research through training of students, who are now among the lead authors and co-authors on these papers, hosting sponsored research on alligators and crocodiles, as well as providing international travel support and faculty research enhancement support for alligator genome resources when I was a research scientist at the Savannah River Ecology Laboratory (SREL)”, said Glenn.

 

John Finger, Jr., a PhD student in the Interdisciplinary Toxicology Program (ITP) and EHS worked with Glenn and colleagues at SREL and Australia to obtain alligator and saltwater crocodile samples used in the project. “Being a co-author on a publication in Science is a great graduation gift”, said Finger, who will graduate next week. “I want to thank the ITP as well as my mentors in EHS, SREL, and Veterinary Medicine, for giving me the opportunity to conduct research on alligators in the USA and saltwater crocodiles in Australia.” Finger is returning to Australia following graduation to continue research on crocodiles.

 

“This research provides the foundation for further work to understand how diseases, such as avian flu, and the effects of environmental toxicants, such as heavy metals, can be shared between humans, birds, reptiles, and other animals”, said Glenn. “Many additional faculty and students at UGA, especially those at SREL, EHS, IOB and the ITP, have contributed to this body of work. I wish there were space to recognize and thank them all for their support, but that would be an extremely long list. I look forward to working with even more colleagues at UGA to use these new resources and new genomic tools to continue research that improves human and environmental health“ added Glenn.

 

Links:

 

https://www.publichealth.uga.edu/ehs/

http://bioinformatics.publichealth.uga.edu/SpeciesTreeAnalysis/index.php

Jingping Li successfully defended her dissertation, titled “Detection of ancient genome duplications in several flowering plant lineages and synte-molecular comparison of homologous regions”

Deli Liu successfully defended his dissertation, titled “Molecular homology between human and dog on mammary and oral cancers”

Dorothy Hammond successfully defended her dissertation, titled “Functional Annotation of Alternatively Spliced Isoforms of Human G Protein-Coupled Receptors”

Congratulations to all three!!!

Institute of Bioinformatics graduate student Daniel McSkimming published a paper in Human Mutation.Click on the title to read the article: ProKinO: A Unified Resource for Mining the Cancer Kinome

Dr. Kissinger has received a two year grant from the National Institutes of Health.  The title of the project is “Resolution of Genome Duplications in Tosoplasma gondii”

Amanda Bouffier published “A MINE Alternative to D-Optimal Designs for the Linear Model” in PLOS One.

To read the article, click here.

Dr. Jim Leebens-Mack, Department of Plant Biology; and Raj Ayyampalayam, QBCG, have published a study in Proceedings of the National Academy of Sciences of the United States.

To read about the study, click here.

To read the study itself, click here.