“It is indeed an honor to be acknowledged in this way – it reflects the strong efforts of many past and present members of the lab,” stated Tarleton, founder of the Center for Tropical and Emerging Global Diseases.
Since his undergraduate days, Tarleton’s research has focused on Trypanosoma cruzi infection, which causes the potentially fatal illness Chagas Disease. Historically, Tarleton’s research has attempted to answer broad questions such as how is immune control initiated and maintained during the infection, how does T. cruzi manage to avoid immune clearance and maintain an infection of decades in host, and what is the relationship between immunity, parasite persistence, and disease development. In an effort to answer these questions and more, Tarleton’s research group has developed tools to better study T. cruzi. They pioneered the use of the gene editing tool CRISPR in T. cruzi. Recently, they applied light sheet fluorescent microscopy to view infection in whole mouse organs. The Tarleton Research Group is also actively pursuing drug discovery for T. cruzi infection in a number of animal models including rodent, dog, and nonhuman primates. Their recent discovery of a dormancy stage in T. cruzi infections has revolutionized their drug treatment research, bringing them one step closer to finding a cure for this infection that affects at least 6 million people.
Tarleton’s work has largely been funded by the National Institutes of Health, the Wellcome Trust, the Burroughs Wellcome Fund, and partnerships with several pharmaceutical groups.
In addition to establishing the Center for Tropical and Emerging Global Diseases at UGA, he has been instrumental in organizing the Chagas Drug Discovery Consortium, which brings together U.S.-based laboratories with international groups. Tarleton is also the founder and current president of The Chagas Disease Foundation. He has been honored with a number of awards, including the Lamar Dodd Outstanding Researcher Award and being named a Burroughs Wellcome Fund Scholar in Molecular Parasitology. In 2017, he was elected as a Fellow of the American Academy of Microbiology.
“Rick’s election as a Fellow of AAAS is recognition of his immense contributions to the study of T. cruzi,” said Dennis Kyle, director of the Center for Tropical and Emerging Global Diseases. “His research has advanced our understanding of immune response to the pathogen, has developed new molecular approaches to study the parasite, and has accelerated drug discovery for Chagas Disease.”
“I value belonging to a society that is focused on global health and lessening the burden of tropical infectious diseases, and I am truly honored to be recognized as a Fellow at a time when a focus on public health, science and climate change is so important for all of us,” said Kissinger.
Kissinger’s research focuses on parasite genomics and the biology of genome evolution. Her research group is trying to answer big questions such as how genomes evolve, what is the fate of horizontally transferred genes, which genes are phylogenetically restricted, and how do organellar genomes evolve? The answers to these questions will increase the understanding of parasite biology and help researchers identify potential drug and vaccine targets.
Kissinger’s research mainly focuses on Apicomplexan parasites, a group of parasites that include species that cause malaria, toxoplasmosis and cryptosporidiosis. Projects in her laboratory include the development of tools for data integration, data mining, comparative genomics and assessing the phylogenetic distribution of genes. Her research group oversees integrated genomic database resources, which are part of the Eukaryotic Pathogen, Vector and Host Informatics Resources (VEupathDB.org), funded by the National Institutes of Health. This resource provides the international research community with open access to data for many pathogenic and related organisms.
Kissinger’s research has been funded by the NIH, the Bill and Melinda Gates Foundation, the Defense Advanced Research Projects Agency, the Wellcome Trust, the United States Department of Agriculture, and the National Science Foundation. Notably, she is the joint principal investigator of a $38.4 million (if all options are exercised) NIH contract that supports VEupathDB.
Kissinger joined the faculty of UGA in 2001. She was a founding member of the Institute of Bioinformatics at UGA to facilitate cutting-edge interdisciplinary research in bioinformatics/computational biology and its applications. Kissinger has been recognized many times for research and leadership. She has been awarded a Creative Research Medal, Faculty Excellence in Diversity Leadership Award and the Richard F. Reiff Internationalization Award from UGA. In 2014, she was awarded a Special Visiting Professorship from Brazil’s national science research agency, and most recently, she was awarded a Fulbright U.S. Scholar award to teach and conduct research at Makerere University in Uganda.
“Being elected as a Fellow of the American Society of Tropical Medicine and Hygiene is recognition of a scientist that has made significant contributions to global public health,” said Dennis Kyle, director of the Center for Tropical and Emerging Global Diseases. “Dr. Kissinger richly deserves this award, and I look forward to her continued leadership in tropical medicine research.”
Megna Tiwari is a second-year Ph.D. trainee in the laboratory of Diego Huet. She is originally from Newport Beach, California and completed her undergraduate degree in Cell, Molecular and Developmental Biology at the University of California, Riverside (UCR). While at UCR, she worked as an undergraduate researcher in the fungal genomics lab of Dr. Jason Stajich for 2 years and co-founded Women in STEM Engaging Riverside (WISER). After graduation, she worked as a blood bank lab technician at LifeStream Blood Bank where she screened for and routinely found blood samples positive for understudied pathogenic parasites. Her fascination with pathogenic parasites led her to seek a thesis-based Master of Science in Biology at California State University, Fullerton under the supervision of Dr. Veronica Jimenez. During this period, Megna worked on understanding the functional and structural relationship of mechanosensitive ion channels found in T. cruzi and cemented her passion for molecular parasitology.
Megna has been awarded a CTEGD T32 Training Fellowship. She currently serves as Vice-president of CTEGD’s Graduate Student Association and New Student Liaison for the Department of Cellular Biology’s Graduate Student Association.
Why did you choose UGA?
My master’s research in parasitology reaffirmed my passion for research in unconventional parasitic pathogens. Therefore, I applied for doctoral programs that would allow me to remain in the field of cell and molecular parasitology and the CTEGD at UGA was the perfect place for me to obtain the best possible training as a parasitologist.
What is your research focus/project and why are you interested in the topic?
The over-reaching research goal of the Huet lab is the investigation of the highly divergent metabolic adaptations of apicomplexans. My research interests in the lab have led me to study the role of the ATP synthase in the apicomplexan Toxoplasma gondii, the causative agent of toxoplasmosis. For my project, I am examining the role of apicomplexan-specific ATP synthase subunits and how they might contribute to the regulation of the ATP synthase function in the parasite.
What are your future professional plans?
Following graduation from UGA, I hope to continue on for a postdoctoral research position in parasitology.
What do you hope to do for your capstone experience?
For my capstone experience, I want to gain an outside perspective and understanding of foreign research culture that I can apply to my own research when I return to the CTEGD.
What is your favorite thing about UGA and/or Athens?
At the CTEGD, I love the collaborative nature. If I am trying to learn a new technique or understand new concepts, I am able to easily walk down the hall to a neighboring lab and get advice. In Athens, for entertainment, I love the endless craft beer scene and I love all the greenery and being able to hike gaps of the Appalachian trail!
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Research shows stronger but less frequent drug doses could be key
Researchers in the University of Georgia’s Center for Tropical and Emerging Global Diseases have found that a more intensive, less frequent drug regimen with currently available therapeutics could cure the infection that causes Chagas disease, a potentially life-threatening illness affecting up to 300,000 people in the United States.
Trypanosoma cruzi is a single-celled parasitic organism that causes Chagas disease. At least 6 million people are infected by T. cruzi, mostly in South America. Current drug therapies have been ineffective in completely clearing the infection and are associated with severe adverse side effects.
A single dose of benznidazole has been shown to be highly effective in killing more than 90% of parasites. However, after a CTEGD team found some of the parasites enter into a dormancy stage, the researchers hypothesized that an intermittent treatment schedule could be effective.
“Current human trials are only looking at giving lower doses over a shorter time period, which is the exact opposite of what we show works.” — Rick Tarleton
“In this system we can see what a single dose of drug does,” said Rick Tarleton, Regents’ Professor in UGA’s department of cellular biology. “Does it make sense to give a drug twice daily when the remaining dormant parasites are insensitive to it?”
The investigators found that giving as little as two-and-a-half times the typical daily dose of benznidazole, once per week for 30 weeks, completely cleared the infection, whereas giving the standard daily dose once a week for a longer period did not.
“Current human trials are only looking at giving lower doses over a shorter time period, which is the exact opposite of what we show works,” said Tarleton.
Since Tarleton’s team worked with a mouse model, how this change in treatment regimen will translate in humans is yet unknown, as are any potential side effects of the higher doses. Adverse reactions already are a problem with current treatments; the hope is that side effects from a less frequent dosage would be more tolerable.
Assessing the success of treatments in Chagas disease is a significant challenge. Tissue samples from infected organisms might not be representative of the entire organ or animal, since low numbers of persistent, dormant parasites can be difficult to detect. Therefore, Tarleton’s group used light sheet fluorescence microscopy to view intact whole organs from infected mice.
“With light sheet fluorescence microscopy, you have a broad view of potentially any tissue in the mouse that allows for dependable assessment of parasite load and persistence,” said Tarleton. “It gives you an incredible view of the infection.”
Using this technology, they learned something new about the dormant parasites: Some were still susceptible to drug treatment. This provides hope that new drug therapies could be developed to target these parasites.
“Discovery of new drugs should continue,” Tarleton said. “We still need better drugs.”
Co-led by assistant research scientist Juan Bustamante and research professional Fernando Sanchez-Valdez in Tarleton’s research group, the study’s findings appear in Science Translational Medicine.
GRA Endowment helps researchers save lives through drug discovery
The Amoeba Summit in Orlando last year is where the importance of her work on drug discovery for deadly amoebae really hit home for Cassiopeia Russell.
It was there she learned the story of an 11-year-old boy who had gone on a family vacation to Costa Rica and was having a great time going down a waterslide at a hot spring there. Days later, he started complaining of a terrible headache. Then he started vomiting. Within a week, he was dead. The cause was a microscopic organism, Naegleria fowleri, living in the warm waters of the spring.
Russell, a doctoral student, had been working in the lab of Dennis Kyle, director of the UGA Center for Tropical and Emerging Global Diseases, for about a year when she was able to attend the conference thanks to a Georgia Research Alliance (GRA) endowment and learn how the research she does in the lab is making a real impact on people’s lives. The GRA was founded with the goal of expanding Georgia universities’ ability to conduct high-level research with the potential of bringing new and innovative products to market. Kyle is the GRA Eminent Scholar in Antiparasitic Drug Discovery, and his endowment enables him to run a 16-person staff of student researchers, postdocs, and research scientists.
“I asked myself at the beginning if I really wanted to work on a parasite this rare,” Russell says. “But if you look at the statistics, this parasite infects mainly young children. Hundreds have died.” She thinks about that every day in the lab.
More commonly referred to as the brain-eating amoeba, Naegleria fowleri is a surprisingly common amoeba found in warm water lakes, ponds, and rivers. When water is forced up the nose—like when diving into a body of water or repeatedly riding a waterslide—the parasite travels to the brain, where it attacks the organ’s cells. Though infections are rare, the brain-eating amoeba kills almost everyone it infects.
One reason Naegleria fowleri is so deadly is because symptoms of the infection resemble those of viral meningitis, a much more common and more treatable disease. “That misdiagnosis and waiting to see if the patient gets better after beginning treatment is wasting valuable time,” says Russell. She’s committed to finding faster, more effective ways to diagnose the condition so patients can get the right medications in time to stop the disease’s progression.
The Georgia Research Alliance really helped me set up this whole operation when I got here. Without the GRA, there’s no way that I could have had this team going for three years.” — Dennis Kyle, GRA Eminent Scholar in Antiparasitic Drug Discovery
As a member of Kyle’s lab, Russell also tests drug compounds to see which ones can kill an amoeba without destroying the human cells it infects. Current drugs used to treat the infection aren’t very effective and are highly toxic.
Despite being almost 99% fatal, not many federal dollars go toward research on brain-eating and other kinds of amoebae. That’s where the Georgia Research Alliance comes in.
“The Georgia Research Alliance really helped me set up this whole operation when I got here,” says Kyle. “Without the GRA, there’s no way that I could have had this team going for three years. This is something that we have concerns about in Georgia. Every summer, we hear of Naegleria fowleri cases on the news. But we don’t have many people worldwide working on it and very few doing the drug discovery needed to come up with a new drug that could save lives. And that’s really our goal.”
The other main area of research in the Kyle lab is malaria and how the parasite becomes resistant to the drugs commonly used to treat it. Additionally, a less commonly studied strain of malaria can go dormant inside its host, effectively hiding in the liver until flaring up weeks, months, or even years later. Kyle and his team were able to develop a model that simulates that dormant phase to test a variety of drugs to find a way to kill the parasite.
But in order to use that model, researchers in the lab must collect parasites from the field. The endowment helped the lab send assistant research scientist Steven Maher to Asia 25 times over the past four years to work with partners in Cambodia and Thailand.
“International travel has definitely changed my life,” Maher says. “Right now, we’re supporting people in Asia and their families, and I think having that human connection is really important. I think all too often we do research and we forget about ‘how is what I’m doing helping real people?’ I think a lot of researchers would benefit from that type of experience.”
The Georgia Research Alliance, private donors, and the UGA Athletic Association are committed to providing researchers like Russell and Maher with opportunities to advance their work on deadly infectious diseases threatening nations around the world.
Melissa Sleda, a Ph.D. trainee is Silvia Moreno’s laboratory, is in her third year at UGA. She is originally from Sandusky, Michigan and attended Lawrence Technological University where she majored in Molecular and Cell Biology with a minor in Chemistry. At UGA, she has held positions as the Secretary for the Cell Bio Grad Student Association (2019-2020), and as Treasurer (2019-2020) and current President (2020-2021) of the CTEGD grad student association.
Melissa Sleda has been awarded a T32 Trainee Fellowship for the 2020-2021 academic year.
Why did you choose UGA?
I chose UGA because of the Integrated Life Sciences Umbrella program. As an incoming graduate student, I was not set on studying a particular organism, and I was excited for the opportunity to rotate in labs across different departments.
What is your research project?
My project seeks to characterize enzymes of the isoprenoid biosynthetic pathway in Toxoplasma gondii and to investigate these enzymes as potential chemotherapeutic targets. The current chemotherapy for Toxoplasmosis is ineffective because it does not eliminate the chronic stage of infection. My project seeks to test drugs that target enzymes of the isoprenoid pathway in both the acute and chronic forms of infection in order to find a more effective chemotherapy.
What are your future professional plans?
My future career goal is to stay in academia and become a professor at a smaller institution with a higher emphasis on teaching and leading smaller research projects. I want to help students at smaller universities gain research experience through classroom labs and one-on-one research projects.
What do you hope to do for your Capstone Experience?
For my capstone experience, I hope to be able to do research in another country to gain a wider perspective of how research is done in other countries. I hope that I am able to do research in a lab that I can learn new techniques that will translate into my research project.
What is your favorite thing about Athens?
My favorite thing about Athens is the warm weather and the great sense of community.
What advice do you have for students interested in this field?
Do things out of your comfort zone because it will help you develop as a scientist.
Support trainees like Melissa by giving today to the Center for Tropical & Emerging Global Diseases.
T32 trainee Alona Botnar is entering her fifth year as a Ph.D. candidate in Dr. Dennis Kyle’s laboratory. She is from Doylestown, Pennsylvania and completed her B.S. in Chemistry with a minor in Biochemistry at the University of Georgia in 2015. During her undergraduate career, she also worked at Janssen, a pharmaceutical company of Johnson & Johnson as a Biologics R&D co-op.
As a graduate student, she was able to spend three semesters teaching Anatomy and Physiology labs here at UGA, and in 2019, she was awarded the Outstanding Teaching Assistant Award sponsored by the Office of the Vice President for Instruction. She also received a graduate school travel award to attend the 2018 annual meeting of the American Society of Tropical Medicine and Hygiene in New Orleans, Louisiana, and an Office for Vice President and Research travel award to attend the 2020 Molecular Approaches to Malaria meeting held in Lorne, Victoria, Australia.
Why did you choose UGA?
Having been at UGA for my undergraduate degree, I was already in love with UGA and Athens and all that they have to offer. I was attracted to the Integrated Life Sciences program because it gives incoming graduate students the freedom to explore a wide range of research topics among 14 different departments before choosing the lab they would ultimately like to join. Furthermore, I found the interdisciplinary approach of the program appealing. I love the Center for Tropical and Emerging Global Diseases because of all the resources available to us as scientists. Not only do we have state of the art microscopy and flow cytometry cores, but we also have very collaborative labs that are happy to share equipment, supplies, and expertise.
What is your research focus?
My research is focused on malaria and addressing significant problems at the stages of development at which the malaria parasite enters a drug-induced dormant period and evades the antimalarial. The mechanism by which the parasite enters drug-induced dormancy and later recrudesces to continue development is currently unknown.
Half the world’s population is at risk of malaria with about half a million people dying each year from it. A majority of these deaths are in children under the age of 5, located mainly in sub-Saharan Africa. While there are 5 species that can infect humans, Plasmodium falciparum is the most lethal and is responsible for a majority of the deaths. Our current arsenal of malaria drugs is failing at an alarming rate as drug-resistant strains of the parasite continue to emerge.
Thus I chose this research project because it is vital that we respond to the challenge of antimalarial drug resistance by not only developing novel drugs but also by understanding the mechanisms the parasite is using to evade the drugs.
What are your future career goals?
I plan on continuing my work in the field of infectious diseases. I am leaning towards industry research but I’m keeping an open mind. Lately, I have been interested in alternative careers available to life science Ph.D.’s such as consulting and being a medical science liaison.
What is your favorite thing about UGA?
UGA football. There’s nothing quite like a fall Saturday in Athens between the hedges. GO DAWGS!
Do you have any advice for a student interested in this field?
It’s never too early or too late to get into the field. Don’t be afraid to send those emails and get involved in research. And always ask questions.
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