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Category: Grants

UGA Researcher Seeks to Unlock Secrets of Malaria Parasite

Donna Huber on January 31, 2018

malaria parasites
Super-resolution microscopy showing malaria parasites infecting human red blood cells. Image credit: Muthugapatti Kandasamy, Biomedical Microscopy Core

Vasant Muralidharan and his research team at the University of Georgia’s Center for Tropical and Emerging Global Diseases are making great strides in understanding how the malaria parasite hijacks red blood cells to cause disease but many of the parasite’s strategies remain elusive.  A new $1.875 million grant from the National Institutes of Health will allow them to continue this research.

Malaria is a parasitic disease that infects nearly 220 million people and kills nearly half a million people every year. Almost all the deaths occur in young children and primarily in sub-Saharan Africa. The parasite Plasmodium falciparum invades human red blood cells which directly leads to malaria symptoms that include headaches, muscle pain, periodic fevers with shivering, severe anemia, trouble breathing, and kidney failure. The parasite can also cause the most severe forms of malaria, such as cerebral malaria which can lead to brain damage, coma and death, and placental malaria, which occurs in pregnancy and can be life-threatening to both the mother and fetus.

Complete control of the infected red blood cell is required for parasites to grow and spread. The malaria parasite remodels the host cell by exporting hundreds of parasite proteins across numerous membranes that transform all aspects of infected red blood cells to suit its needs. The export of these proteins by P. falciparum to the host red blood cells is a unique parasite-driven process that is associated with many of the clinical manifestations of malaria, including death. The mechanisms which these proteins are exported are unknown.

“Exported proteins, many of them absolutely essential for the growth of the parasite, are recognized and sorted throughout the trafficking process by dedicated machinery that we have only now begun to understand,” said Muralidharan, assistant professor in the department of cellular biology.

His lab hopes to reveal unique protein trafficking mechanisms of P. falciparum that may be targets for antimalarial drug development.

 “We expect that this project will significantly advance our understanding of the protein export pathway in P. falciparum and how key decisions are made within the parasite that usher exported proteins to their site of action in the infected red blood cells,” concluded Muralidharan.

National Institutes of Health Award R01 AI130139 “Elucidating the trafficking mechanisms of effector proteins to the Plasmodium infected red blood cell.”

UGA Researchers Receive NSF Grant to Study Hormone Regulation in Mosquitoes

Donna Huber on September 6, 2017

mosquito

Athens, GA–Mosquitoes transmit diseases such as Zika virus, dengue, and malaria to people and other vertebrates worldwide. In a newly funded National Science Foundation (NSF) project, Michael Strand and Mark Brown, both professors in the Department of Entomology and members of the Center for Tropical and Emerging Global Diseases, hope to gain new insights into how hormones coordinate immune responses with reproduction.

The immune and reproductive systems of all animals, including mosquitoes, require large amounts of energy but how these energetic demands are regulated at the molecular level are poorly understood. How immune defenses are regulated relative to other functions like reproduction is of long-standing interest and the main goal of this project is to answer this question.

Strand and BrownMosquitoes provide an interesting system for addressing these issues because almost all species must feed on blood from a vertebrate host, such as humans or another animal, to reproduce.  However, blood feeding exposes mosquitoes to microorganisms that cause disease in mosquitoes, the vertebrate hosts mosquitoes feed upon, or both.  Background studies by Strand and Brown have shown that certain hormones co-regulate reproduction and immune defense.

“What we hope to characterize in this project are the biochemical pathways these hormones interact with, and how these pathways affect the ability of mosquitoes to defend themselves from infection,” said Strand. “We also will learn whether these pathways function similarly or dissimilarly between species.”

The fundamental questions about reproduction and immunity that this project is designed to answer apply not only to mosquitoes but to all animals. “The information we generate will also potentially provide information that can be applied toward reducing mosquito reproduction and transmission of pathogens that cause human disease,” said Strand.

NSF requires grant recipients to engage in activities that have broader impacts that enhance STEM education and improve science literacy in the general public. “The public at-large generally knows that mosquitoes can transmit human diseases, but people often do not understand how disease transmission occurs or why some mosquito species are disease vectors but most are not,” said Strand. In conjunction with Georgia 4-H and the Cooperative Extension Program at UGA, teaching materials for middle and high school students will be developed that explain disease transmission, the mosquito life cycle, and strategies for controlling vector populations.

National Science Foundation Award #1656236 “Endocrine regulation of immunity and reproduction in mosquitoes”

Writer: Donna Huber

Contact: Michael Strand, Mark Brown

Researcher receives $5.2 million to develop affordable diagnostic test for Chagas disease

Donna Huber on September 21, 2016

Dylan Orr

Athens, Ga. – An international team of researchers led by infectious disease experts at the University of Georgia has received $5.2 million from the National Institutes of Health to develop a more accurate, affordable diagnostic test for Chagas disease, a parasitic infection that kills more than 50,000 people each year in Central and South America.

Caused by the parasite Trypanosoma cruzi and spread by blood-feeding insects commonly known as “kissing bugs,” Chagas disease is considered by many to be the most neglected of the neglected tropical diseases. While it is endemic to Latin America, Chagas disease is a growing threat in the U.S. and Europe.

Currently, there are only two drug treatments available; however, their usage is limited due to severe adverse reactions and the length of treatment required.

“Fortunately, there are a number of new drug discovery efforts in Chagas disease. But a major limitation is the difficulty in comparing the relative efficacy of current drugs to newly developed ones,” said Rick Tarleton, UGA Athletic Association Distinguished Research Professor of Biological Sciences in the department of cellular biology and Center for Tropical and Emerging Global Diseases. “One simply can’t wait for 10 years (as current protocols require) to determine if a new drug is better than the existing ones.”

In Chagas disease, the number of parasites in chronically infected individuals is extremely low, making detection of parasites an unreliable test to determine if an individual is infected. Instead, the researchers have focused on the body’s response to infection by measuring the unique antibodies that the immune system creates in response to exposure to T. cruzi.

Tarleton and his UGA colleagues have already developed a successful multiplex blood test that measures antibodies to multiple T. cruzi proteins. While their test has proven to be useful in the laboratory, it is also expensive.

The primary goal of their current project is to make the test more sensitive by expanding the number of T. cruzi antibodies it can detect. But the researchers are also developing techniques to make the test more affordable so that it can be used in diagnostic centers in endemic countries.

“By monitoring a broader range of immune responses, we can achieve a rapid and reliable detection of changes in these responses after treatment. And moving from the current bead-based assay to an array platform makes the reagents and the detector for reading the assay much more affordable,” said Tarleton.

The “gold standard” for determining a cure is for a patient to convert from seropositive to seronegative, meaning that a blood test does not detect any T. cruzi antibodies. The conventional blood test requires a minimum of 24 months to show a decline in antibody response, and complete conversion to a negative blood test can take up to 10 years.

Over the past 12 year, the Tarleton laboratory and CONICET research scientist Susana Laucella’s laboratory in Argentina have shown antibodies tested by the multiplex method are potential surrogate indicators of treatment success. They believe this method will detect significant decline in antibody levels in less than 12 months.

In an effort to more rapidly determine treatment success, the project will also investigate additional potential markers of patients being cured, including antibodies to carbohydrate epitopes and changes in numbers of plasmablasts, the cells that secrete antibodies.

“We are looking for the earliest signs of treatment efficacy,” said Tarleton. “As parasite numbers are reduced due to treatment, we expect, based on data from other systems, that one of the first detectable changes will be in the immune cells that are responding to the presence of parasites and producing antibodies, the plasmablasts.”

The researchers will also be exploring the phenomenon of spontaneous cure-a cure in the absence of treatment-as only anecdotal information is currently available.

“The immune response to T. cruzi infection is actually very strong and as a result, spontaneous cure occurs,” said Tarleton. “However the frequency of cure without treatment is not known, nor are methods available that discriminate between those with active, chronic infections and those who have cured.”

Approximately 20 percent of individuals receive mixed results from conventional blood tests for T. cruzi infection. This is a large number of potentially infected people to leave untreated. However, current therapies have such severe side effects doctors often do not prescribe. Additionally, understanding why some individuals can “cure themselves” could lead to new treatments for the disease.

“The key to the success of this project will be the bringing together of basic research findings with great technology and access to patient groups and their samples-some collected over decades. That is what the partners in this work collectively bring to the problem,” said Tarleton.

Tarleton is joined by collaborators at the Blood Systems Research Institute, the University of California, Irvine, Emory University as well as partners in Argentina and Brazil. Their project is supported by the National Institutes of Health under award number R01-AI125738.

UGA Center for Tropical and Emerging Global Diseases
The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions for at-risk populations. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information, see ctegd.uga.edu.

Writer: Donna Huber
Contact:Rick Tarleton

UGA researcher receives $1 million for cryptosporidium research

Donna Huber on November 2, 2015

Boris Striepen

Athens, Ga. – Researchers at the University of Georgia have received $1 million from the Wellcome Trust and the Bill & Melinda Gates Foundation to speed the development of new drugs for the treatment of cryptosporidiosis, a major cause of diarrheal disease and mortality in young children around the world.

Cryptosporidiosis is caused by cryptosporidium, a microscopic parasite commonly spread through tainted drinking or recreational water. There is currently no vaccine and only a single drug of modest efficacy available to treat cryptosporidiosis.

“Cryptosporidiosis is a tremendous public health challenge,” said Boris Striepen, Distinguished Research Professor in Cellular Biology in the Franklin College of Arts and Sciences and a member of UGA’s Center for Tropical and Emerging Global Diseases. “We are extremely grateful to the Trust and the Foundation for providing generous support and leadership to drive a global research agenda to face this challenge.”

Cryptosporidium is notoriously difficult to study in the laboratory, and this has stalled the development of better treatments. But earlier this year, Striepen and his research group created new tools to genetically manipulate the parasite, and his team will use funds from the Wellcome Trust and Gates Foundation to leverage this new technology and speed drug discovery.

The Wellcome Trust’s Pathfinder Award of $244,000 will support a collaboration between UGA and the Novartis Institute for Tropical Diseases, a public-private partnership between the pharmaceutical company Novartis and the Singapore Economic Development Board.

The Novartis Institute for Tropical Diseases “has been at the forefront of discovery of new treatments for malaria, tuberculosis and sleeping sickness,” Striepen said. “Engaging a group with this track record to the problem of cryptosporidiosis will be game changing.”

The primary goal of the joint project is to develop better assays to evaluate the effectiveness of drugs in cell cultures and mice. These assays will be used to discover novel candidate drugs using the Novartis Institute for Tropical Diseases’ large collection of candidates.

A $775,000 grant from the Bill & Melinda Gates Foundation will support the development of genetic technology to discover specific drug targets within the parasite, which will ultimately help enhance drug potency and reduce side effects.

Initially, the project will validate targets for drugs for which predictions for likely candidates can be made from prior experience-in particular from the related malaria parasite. In a second phase the project will discover the yet unknown targets of novel drugs.

“The need for effective treatment of cryptosporidiosis is critical, both nationally and internationally. This highly welcome initiative is a major step for those millions of children who globally suffer from this devastating disease,” said Dan Colley, director of CTEGD and former director of the CDC’s Division of Parasitic Diseases.

For more information on the UGA Center for Tropical and Emerging Global Diseases, visit http://ctegd.uga.edu/.

The Wellcome Trust is a global charitable foundation dedicated to improving health. For more information, visit www.wellcome.ac.uk.

Writer: Donna Huber
Contact:Boris Striepen

UGA receives $1.25 million for training of tropical, emerging global diseases researchers

Donna Huber on August 13, 2015

trainee Charles Rosenberg

Athens, Ga. – The University of Georgia’s Center for Tropical and Emerging Global Diseases was awarded $1.25 million by the National Institutes of Health to continue training graduate and postdoctoral students over the next five years who can help address the growing threats of parasitic diseases.

Every year, diseases caused by protozoan and helminth parasites are responsible for more than a million deaths and cause hundreds of millions more cases of severe or subtle morbidity due to chronic infections lasting years.

“The University of Georgia is uniquely positioned as a training ground for the next generation of parasitology and tropical diseases researchers,” said Silvia Moreno, a professor of cellular biology in the Franklin College of Arts and Sciences and co-director of the center’s T32 trainee program.

The internationally recognized research center brings together the largest number of laboratories in the U.S. that collectively conduct research on the full gamut of parasite diseases. These diseases are highly prevalent in sub-Saharan Africa, South America and Asia. Often they are the consequence and cause of poverty. They also are increasingly emerging or re-emerging in the U.S. and other industrialized nations.

The CTEGD training program is currently in its 10th year. Past trainees have gone on to successful careers as staff scientists at the Centers for Disease Control and Prevention and as faculty, postdoctoral scholars or medical and veterinary scientists at leading universities and research institutes.

“The breadth and culture of our program instills trainees with the ability to not only translate basic scientific findings into tool development and the implementation of interventions, but also to identify and formulate fundamental research questions beyond the context of parasitic disease itself,” Moreno said.

“This program is very attractive to students,” said Boris Striepen, Distinguished Research Professor of Cellular Biology in the Franklin College and co-director of the training grant. “We have had many more strong candidates than training slots.”

To address this issue, the new NIH award will double the number of postdoctoral trainees from one to two each year, and matching funding from UGA’s Office of the Vice President for Research will support two predoctoral trainees in addition to the three graduate students supported by the training grant each year.
“This institutional matching support is tremendously important when competing for NIH training grants,” said Dan Colley, CTEGD director, who was the T32 training grant program director for its first 10 years.

Trainees in the program build upon their background in biomedical sciences through specialized courses and research mentored by one or more CTEGD faculty. The program is unique in that students can also broaden their perspective on the global aspects of parasitic diseases through a capstone experience, which typically takes students away from the UGA campus for four to eight weeks. Many of the previous trainees have conducted field studies in a disease-endemic country.

“My capstone experience in Kenya provided an exceptional opportunity to gain experience both working in the field and in a laboratory in a developing setting,” said Briana Flaherty, a doctoral student in the CTEGD and the department of infectious diseases. “This short time has had a profound impact on my future interests and career goals.”

The many international collaborations of the center’s faculty provide a wide variety of opportunities to the trainees. Over the last nine years, graduate students have worked in Haiti, Tanzania, Argentina, Thailand and Kenya. The Office of the Vice President for Research also has committed funds over the next five years to assist in the provision of these experiences on the T32 training grant.

“We in CTEGD are extremely pleased that NIH has seen fit to fund this T32 training grant for an additional five years,” Colley said. “It is an investment in our new program directors, Drs. Striepen and Moreno, and in CTEGD’s commitment to high-quality training of the next generation in this important area of parasitic disease-related research.”

The grant funding is provided under NIH award number 3T32AI060546.

UGA Center for Tropical and Emerging Global Diseases
The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information, see http://ctegd.uga.edu/.

Writer: Donna Huber
Contact:Boris Striepen

UGA researchers to develop new treatment for Chagas disease

Donna Huber on January 28, 2015

Rick TarletonAthens, Ga. – University of Georgia researchers in collaboration with Anacor Pharmaceuticals have received a $5.3 million grant from the Wellcome Trust to develop a new drug for the treatment of Chagas disease, which they hope will be ready to enter clinical trials by 2016.

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.

Between 10 and 20 million people, mostly in Central and South America, are infected with Trypanosoma cruzi, and Chagas disease kills more people in Latin America than any other infectious disease—including malaria, tuberculosis and HIV. An increasing number of cases are also being documented outside the normal high transmission areas, including in the U.S. and Europe.

“The two drugs commonly used to treat Chagas disease, benznidazole and nifurtimox, require a long course of therapy and have a number of serious side effects,” said Rick Tarleton, UGA Athletic Association Distinguished Research Professor of Biological Sciences in the department of cellular biology in UGA’s Franklin College of Arts and Sciences. “This combined with the fact that many isolates of the parasite are resistant to these existing drugs emphasizes the tremendous need for new treatments.”

Tarleton’s laboratory will work in partnership with Anacor, a biopharmaceutical company focused on discovering, developing and commercializing novel small molecule therapeutics derived from its boron chemistry platform.

Anacor pioneered the development of a boron-based drug class called oxaboroles, which researchers hope will serve as the foundation for a new Chagas therapy.

Boron is a naturally occurring element that is found commonly in fruits, vegetables, milk and coffee, but it is only recently that scientists have begun exploring the potential of boron-containing small molecules in drug development for a variety of infectious agents.

“These new drug classes have a lot of potential for a variety of diseases, including many of the most neglected diseases of humans,” said Tarleton, who is a member of UGA’s Center for Tropical and Emerging Global Diseases. “We have worked with Anacor to identify some potent lead compounds for use in Chagas disease, and this funding will help turn those leads into effective drugs.”

For more information about Anacor, see www.anacor.com.

UGA Center for Tropical and Emerging Global Diseases
The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions for at-risk populations. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information, see ctegd.uga.edu.

Writer: James Hataway
Contact:Rick Tarleton

Gates grant supports UGA’s continued fight against infectious disease

Donna Huber on January 13, 2015

Dan Colley
Environmental portrait of UGA Research Professor Dan Colley in his lab inside the Coverdell Building.

Athens, Ga. – The University of Georgia Research Foundation has received an additional $710,000 from the Bill and Melinda Gates Foundation to expand its research into the elimination of schistosomiasis, a neglected tropical disease affecting millions of people throughout most of Africa and some of Asia, the Middle East and the Americas to include studies on control and elimination of intestinal worms that infect almost 2 billion people globally.

This grant adds to the more than $22 million in support awarded to UGA by the Gates Foundation since 2008, when researchers in the Schistosomiasis Consortium for Operational Research and Evaluation, or SCORE, began looking for ways to gain control of and ultimately eliminate the disease that causes more than an estimated 200,000 deaths per year in sub-Saharan Africa alone, according to the World Health Organization.

“We’ve made great progress in our understanding of this disease and what must be done to stop it,” said Dan Colley, director of UGA’s Center for Tropical and Emerging Global Diseases and principal investigator for the project. “This latest supplement will expand our research to include parallel studies on the debilitating and even more widespread soil-transmitted helminthes, round worm, whipworm and hookworms, and it will carry the project forward to 2018.”

Schistosomiasis is a parasitic disease caused by several species of worms belonging to the genus Schistosoma. The parasite’s life cycle begins when human waste containing eggs—from the worms living in a patient’s blood vessels—enters the water, whereupon the eggs hatch.

Free-swimming hatchlings then seek out and infect freshwater snails. The hatchlings mature and replicate inside the snails, eventually releasing tens of thousands of larval parasites that burrow into the skin of humans who wade, swim, bathe or wash in the water.

The infection can be treated with the drug praziquantel, but patients are frequently re-infected when they return to the water where they work or play. The soil-transmitted worms also are treatable with drugs, but reinfection rates are high due to the contaminated environment in which many people live.

“Controlling schistosomiasis and soil-transmitted worms isn’t as simple as diagnosing the disease and prescribing a treatment,” said Colley, who is a microbiologist in UGA’s Franklin College of Arts and Sciences. “We have to consider people’s behavior, their environment, social and cultural practices as well as all the medical and field data required to develop strong treatment programs.”

SCORE researchers are working with local African communities and governments to evaluate mass drug administration, snail control, diagnostic tests and sanitation and hygiene changes designed to slow or stop disease spread.

One of their first major studies, representing more than five years of fieldwork and data collection, will be ready for analysis this year. They hope these and subsequent results will ultimately reveal the right combination of techniques necessary to gain control of the disease and sustain that control until it is eliminated.

“It’s difficult to explain what a monumental task this is,” Colley said. “The project requires the hard work of dozens of partners in academia, government and non-profit organizations and hundreds of field and laboratory workers, all of whom have been invaluable in fighting these diseases that globally affect so many of those in poverty.”

UGA Center for Tropical and Emerging Global Diseases
The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions for at-risk populations. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information, see ctegd.uga.edu.

Writer: James Hataway
Contact:Dan Colley