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Category: CTEGD Blog

Trainee Spotlight: Corey Rennolds

Corey Rennolds

 

My name is Corey Rennolds, and I’ve been a postdoctoral researcher in Tania Rozario’s lab at UGA since August 2022. I’m originally from Cobb County, GA, where I went to grade school, received my B.S. in Biology from Georgia Tech in 2013, and completed my PhD at the University of Maryland, College Park in 2022.

What made you want to study science?
The big bucks, baby!! More honestly, I enjoy learning how things work for its own sake, and I liked the idea of a career spent always learning more about how things in the world work. I started as an undergraduate in engineering but quickly switched to biology when I realized that I was more interested in natural systems than artificial ones (and that I wasn’t very good at calculus). I have other interests of course, but science translates the most smoothly of those into a stable and rewarding way to make a living.

Why did you choose UGA?
I’m originally from the Atlanta area and spent a lot of time in Athens when I was an undergraduate, even though I went to Tech. Now living and working here feels like coming home for me. I finished my PhD and wanted to continue in a research-oriented direction as a postdoc in an academic setting, and UGA is a big, well-funded institution with a strong biology contingent and several faculty in the ballpark of my more narrow expertise. Altogether, it seemed like a good fit.

What is your project/research focus and why did you choose this research focus?
Dr. Rozario learned during her own postdoctoral work that the rat tapeworm Hymenolepis diminuta requires a population of stem cells maintained in the adult worm in order to grow and regenerate, but there was little information on how these cells are activated, how many different varieties there are, their plasticity, and how they differentiate into mature tissue types. Dr. Rozario wanted to hire a postdoc with experience in transcriptomics and regenerative biology in non-model organisms, which is fortunately my background. I thought the project was really interesting with opportunity to do novel work that would stand out. It also gives me the chance to learn a lot of cutting-edge techniques that can be valuable for my research in the long term.

Have you received any awards or honors?
Aside from the T32 postdoctoral fellowship through the CTEGD, I received a few scholarships, fellowships, and other awards during graduate school, including small research grants from Sigma Xi, the Cosmos Club, and Washington Biologists’ Field Club. I would also be remiss not to mention my first-place finish in the most recent CTEGD chili cook-off.

What are your career goals?
I spent most of graduate school as a TA (tip for prospective graduate students: ask your PI about funding!) and so racked up plenty of experience in teaching and discovered that I really enjoy doing it. I want teaching to be a significant part of my career activities going forward, as opposed to just full-time research. Research-wise, though, I am interested in building an independent research program focused on bridging evolutionary-developmental biology with comparative and ecological physiology. To put it simply, I want to study how living things grow, develop, and repair themselves, where and how they get the resources to do these things, and how those processes are affected by environmental factors, including over evolutionary timescales. Working with intestinal parasites is definitely an interesting and challenging context for thinking about these sorts of broad questions.

What is your favorite thing about UGA and Athens?
Athens is close enough to Atlanta to access its amenities but far enough away to be its own ecosystem free of the sprawl. It’s big enough to have a little of everything, including a vibrant and diverse arts scene, but small enough to get to know most of the people in whatever sphere you want to be involved in. The university offers plenty of opportunities for both intellectual stimulation and less-intellectual partying. The traffic isn’t too bad.

Any advice for a student interested in this field?
Don’t settle too much. It is perfectly fine to have standards during your education and assert yourself when called for. You should study what you enjoy, attend school somewhere you want to be, and work with people you get along with. Not everything will be perfect and you should learn when to compromise, of course, but it’s your life and your career. If something isn’t working out, make a change, and be open to alternative paths—if I didn’t take the initiative to change course when I did, I wouldn’t be a biologist now. Think carefully about what is in your best interest personally and professionally in both the short and long term. Also, learn when to identify opportunities to learn something useful or gain valuable experience. In CTEGD, there are a lot of different technical resources, training and professional development opportunities, and diverse faculty expertise; make use of all these things, it’s what they’re there for!

 

Support trainees like Corey by giving today to the Center for Tropical & Emerging Global Diseases.

Diego Huet zeroes in on parasite that affects thousands each year

Diego Huet
Diego Huet, assistant professor in the College of Pharmacy and the Center for Tropical & Emerging Global Diseases, studies parasites that cause disease in both humans and animals. His lab has ramped up a project to better understand the biology of Toxoplasma gondii , an organism carried by cats that is related to the parasite that causes malaria. (Photo by Lauren Corcino)

 

From an early age, Diego Huet has been interested in the unusual and fascinating found in the natural world.

His early encounters with animals, plants and insects nurtured his curiosity about nature. Their striking colors and sometimes strange shapes drew his interest, and even today he continues to capture them through macro photography. It was this fascination that led him to the parasite he studies today.

“I was always drawn to ‘unconventional’ or ‘weird’ science,” said Huet, an assistant professor in the College of Pharmacy’s Department of Pharmaceutical and Biomedical Sciences and member of the Center for Tropical and Emerging Global Diseases. “But I also wanted to be hands on, which is what led me to molecular and cellular biology.”

As a doctoral student, Huet began studying Trypanosoma brucei, a parasite commonly transmitted by the tsetse fly. Wanting to study a different parasite as a postdoctoral researcher, he was torn between studying Plasmodium, which is the causative agent of malaria, and Toxoplasma gondii, a related parasite that is carried by cats. Both parasites, which belong to a group of organisms called apicomplexans, cause diseases in humans and animals, and there remain large knowledge gaps in our basic understanding of them. Ultimately, he chose the latter.

Plasmodium is difficult to manipulate,” Huet said. “Toxoplasma is related to Plasmodium, but is easier to work with because it isn’t as complex, and what we learn about Toxo could also increase our knowledge of Plasmodium.”

Just as yeast and fruit flies are used as model organisms to study human biology, Toxoplasma can be used as a model for shared features of apicomplexan biology.

Besides aiding in the understanding of other parasites of human and veterinary concern, including parasites that cause malaria in tropical and subtropical regions of the world, Toxoplasma gondii also causes human and animal disease. More than 40 million people in the U.S. are estimated to carry T. gondii. Although most never show symptoms, it poses a major health threat to immunocompromised individuals and pregnant women as it can lead to miscarriage and birth defects. Toxoplasmosis, the disease caused by Toxoplasma, is considered a leading cause of death among foodborne illnesses though it can also be transmitted through contact with cat feces.

The Centers for Disease Control and Prevention has it listed as a neglected parasitic infection in the United States and a target for public health action.

Huet joined the faculty at the University of Georgia in 2019 and has developed a robust research program to expand knowledge of the basic biology of Toxoplasma.

Madelaine Usey
Madelaine Usey is a cellular biology graduate student in the Huet Laboratory.

In a recently published study in “mBio”, cellular biology doctoral candidate and Huet Lab member Madelaine Usey looked at proteins critical for mitochondrial function in T. gondii. The mitochondrion is considered the “powerhouse of the cell,” but it is an enzyme called ATP synthase that generates the cellular energy.

“Our findings are really exciting for drug discovery,” Usey said. “Many of the proteins that make up the ATP synthase are different in Toxoplasma compared to other organisms. In this study, we were able to figure out what two of those novel subunits are doing—they act as scaffolding for this enormous ATP synthase complex.”

These proteins are unique to Toxoplasma and could be used in drug discovery as targets since they are important for mitochondrial functioning.

Another project in Huet’s laboratory, which recently received funding through a grant from the National Institute of General Medical Sciences, investigates how organelles within the parasite communicate.

“Traditionally, we thought organelles send and receive calcium and other metabolites in much the same way we receive a package through the mail,” Huet said. “Cells form vesicles to transport materials to specific locations within the cell. The vesicles are labeled with proteins that act like a postal address, telling the vesicle where to go.”

However, cells can also exchange material through another process.

“When the organelles’ membranes get close together, they form what is called a membrane contact site,” Huet said. “In this case it is more like one organelle hand delivers the package to another.”

A membrane contact site is a specialized protein structure that organelles use for intracellular communication. However, it is not a well understood structure in apicomplexans. In addition, these parasites have additional organelles not found in traditional models like humans and yeast, so Huet is trying to understand how the organellar communication is happening in apicomplexans using Toxoplasma as a model.

Identifying such proteins and their functions could lead to better drug targets and better drug treatments, which all the neglected parasitic diseases need.

“Toxo’s genome isn’t well annotated,” Huet said. “Finding membrane contact site proteins is an arduous task—it’s a goal of my lab to identify some of them and their involvement in Toxoplasma membrane contact sites.”

 

This article was first published at https://research.uga.edu/news/diego-huet-zeroes-in-on-parasite-that-affects-thousands-each-year/

Undergraduate Research Experience Sparked Interest in Parasitology for Graduate Student

doctoral student Victoria Mendiola

My name is Victoria Mendiola and I am a PhD candidate in Dennis Kyle’s lab studying drug-induced dormancy in Plasmodium falciparum, the parasite responsible for malaria. I have been at UGA for four years but originally received my BSc in Biology and MSc of Integrative Biology from Kennesaw State University in Kennesaw, GA.

My interest in infectious diseases stems from an NSF REU research internship where I was first introduced to the complexities of parasite-host interactions on an organismal level by studying hookworm infections in South American fur seals (SAFS) in the Gottdenker Lab at UGA’s College of Veterinary Medicine.

During my REU, I fell in love with Athens and the scientific community in the area but the large number of tropical disease parasitologists solidified my reason for choosing UGA to continue my studies.

My doctoral research focuses on developing novel high-content imaging assays to incorporate Artemisinin-induced dormant Plasmodium falciparum recovery into the current understanding of drug treatment, therapeutics, and prevention. Of the species of Plasmodium that infect humans, P. falciparum is the deadliest and, unfortunately, is becoming resistant to current treatment options.

In August 2023, I received the CTEGD Training in Tropical and Emerging Global Diseases fellowship. In addition to providing up to two years of funding, there is also the opportunity for a capstone experience. I plan to use the capstone project opportunity to gain essential in-field, on-site training to complement my current wet lab skillset.

My long-term career goal is to utilize my diverse training in physiology, developmental biology, cellular biology, and infectious diseases to design, optimize, and implement phenotypic and behavioral assays in the context of drug discovery and parasite homeostasis.

For students who are interested in joining the Center for Tropical and Emerging Global Diseases, I suggest they take every opportunity to talk to other researchers in and out of their field and organism of study. The sense of community within the CTEGD is unparalleled and should be utilized at every given opportunity. The friends I have made in and outside of the lab is one of my favorite things about being here at UGA (but the local festivals are really fun too).

Support trainees like Victoria by giving today to the Center for Tropical & Emerging Global Diseases.

UGA researchers received prestigious grant to develop malaria drug

by Amy Horton

Chet Joyner and Steven Maher
Principal Investigators Chet Joyner (left) and Steven Maher (right). Photo credit: Donna Huber

 

New compound targets P. vivax, source of recent U.S. infections

Two University of Georgia researchers have been awarded approximately $770,000 from the Global Health Initiative Technology (GHIT) Fund to develop a new drug to kill the dormant liver stages of Plasmodium vivax, the most widespread of the malaria parasites. This amount is part of a total of JPY 334,238,778 awarded by the GHIT Fund to a partnership consisting of UGA, Medicine for Malaria Venture and Mitsubishi Tanabe Pharma Corporation.

P. vivax often persists in the liver of patients, causing a relapse infection following treatment of the symptomatic blood infection,” said Steven Maher, associate research scientist in the Office of Research’s Center for Tropical and Emerging Global Diseases (CTEGD). “In many parts of the world, relapses account for the majority of total P. vivax cases.”

The announcement comes on the heels of reports of the first locally acquired cases of malaria in the United States in 20 years. In the summer of 2023, seven cases of locally acquired P. vivax malaria were reported in Sarasota, Fla., and one in Cameron County, Texas. These are in addition to a case of P. falciparum diagnosed in a Maryland resident living in the National Capital Region.

Most malaria cases diagnosed in the United States occur in people who have traveled to countries in South America, Africa, and southeast Asia where malaria is endemic. While locally acquired mosquito-transmitted malaria cases can occur, as Anopheles mosquito vectors exist throughout the United States, they are rare. The last reported outbreak was in 2003 when eight cases of locally acquired P. vivax malaria were identified in Palm Beach County, Fla.

The GHIT award will allow Maher and Chet Joyner to develop a compound series drug-screening program. Joyner is an assistant professor in the College of Veterinary Medicine’s Department of Infectious Diseases and Center for Vaccines and Immunology and jointly appointed to CTEGD.

Microscopy image of Plasmodium vivax
Microscopy image of a P. vivax dormant (left, green) and growing (right, green) liver parasites inside of human liver cells (nuclei in purple). Image taken using 100x magnification. The dormant form survives most antimalarial treatments, but the new series of antimalarials kills both forms of the parasite. (Image credit: Wayne Cheng)

The compound series identified by Maher, the result of testing more than 100,000 samples using infected liver cells, is the first new chemical class discovered in more than 70 years with efficacy against the persisting liver stage. Over the next two years, Maher and Joyner will be collaborating with Medicine for Malaria Venture and Mitsubishi Tanabe Pharma Corporation to alter the chemistry of the compound to improve drug-like properties, including half-life and potency, necessary to achieve single dose criteria.

“Discovering a drug to kill dormant, non-proliferating cells is extremely difficult, yet with the novel assay the team developed we now have the first new target and drug class with potential to accelerate global malaria elimination efforts,” said Dennis Kyle, director of the CTEGD.

The current drug class used to treat P. vivax malaria, 8-aminoquinolines, often results in serious side effects and cannot be administered to pregnant women, who are one of the patient groups most in need of treatment.

“We have the first validated compound that kills vivax while it lies dormant in the liver,” Joyner said. “We hope in the next two years to help advance the new compounds to clinical testing.”

Lisa K. Nolan, dean of the College of Veterinary Medicine, said the work Maher and Joyner are doing could deliver a better quality of life to millions of people around the world.

“This great research is a shining example of our commitment to translational research, which will take this drug from the lab to preclinical testing to the patient rapidly,” Nolan said.

Chagas disease research in the news

Rick Tarleton

DDN Dialogues

Rick Tarleton was recently interviewed for the Drug Discovery News podcast. Listen as he talks about his research into new drug treatments for Chagas disease.

A written transcript is available on DDN’s website.

KFF Health News

Rick Tarleton, along with Drew Etheridge‘s lab, was featured in a KFF Health News story about Chagas disease that has been picked up by a number of media outlets.

KFF Health News (Spanish translation)

NBC News

California Healthline

News Medicine

CNN

Sun Herald

The San Diego Union-Tribune

Christopher West named 2023 Distinguished Research Professor

Christopher West

Christopher West, head of the Department of Biochemistry and Molecular Biology, a researcher in the Complex Carbohydrate Research Center and a member of CTEGD, belongs to a small group of internationally recognized parasite glycobiologists. His rigorous, transformative research explores cellular processes involving various structures, enzymes and roles of glycans, or sugar chains. His studies have identified fundamental cell-to-cell mechanisms of environmental sensing and signaling in glycobiology. Some of his seminal discoveries involve the biosynthesis and roles of novel glycan molecules in the model organism, Dictyostelium discoideum. One of his crucial contributions to glycobiology has been to describe at molecular resolution that organism’s biochemical response pathway to altered oxygen levels, allowing it to respond to its environment’s available oxygen. Since arriving at UGA, he has translated these findings to an opportunistic human pathogen, Toxoplasma gondii, which can grow and infect cells in low-oxygen environments. His research with collaborators at UGA and internationally has opened a new field of oxygen-sensing in protists, exploring how this environmental factor can control the behavior and virulence of pathogenic parasites.

All the pieces matter: UGA researchers collaborate to solve malaria puzzle

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

They say what doesn’t kill you makes you stronger. Whoever coined that adage had probably never heard of Plasmodium.

It’s a microscopic parasite, invisible to the naked eye but common in tropical and subtropical regions throughout the world. Each year, millions of people are infected by Plasmodium and exposed to an even more debilitating—and often deadly—disease: malaria.

Malaria is one of the deadliest diseases known to man. It can lead to extreme illness, marked by fever, chills, headaches and fatigue. More than half the world’s population is at risk of contracting the disease, and those who develop relapsing infections suffer a host of associated costs.

Limited educational opportunities and wage loss lead to an often unbreakable cycle of poverty. Vulnerable populations are most at risk.

“When I’m teaching in an endemic area like Africa, it isn’t unusual to find a student who needs to sleep during part of the workshop because they have malaria,” researcher Jessica Kissinger said.

It’s a challenge she and her collaborators in the University of Georgia’s Center for Tropical and Emerging Global Diseases (CTEGD) are trying to combat.

When the Center was established in 1998, there were only a couple of faculty members studying Plasmodium. Now, 25 years later, it has become a world-class powerhouse of multidisciplinary malaria research. Scientists examine various species of the dangerous parasite, studying its life cycle and the mosquito that transmits it.

While Plasmodium seems to have superpowers that allow it to evade detection and resist treatment, CTEGD researchers are working together to innovate and transfer science from the lab to interventions on the ground.

A 50,000-piece puzzle with no edges

Plasmodium is a complex organism, and studying it is like putting together a jigsaw puzzle. Some researchers contribute pieces related to the blood or liver stages of the parasite’s lifecycle, while others provide insights about hosts interactions. One way UGA’s research connects with the global effort to eradicate malaria is PlasmoDb—a resource derived in part from Kissinger’s research that is now part of a host of databases under the umbrella of The Eukaryotic Pathogen, Vector and Host information Resource (VEuPathDB).

“Our group has been able to help many others when their research question crosses into an –omic,” Kissinger said, referring to in-house shorthand for domains like genomics, proteomics and metabolomics.

Kissinger, Distinguished Research Professor of genetics in the Franklin College of Arts & Sciences, became interested in malaria and Plasmodium during her postdoctoral training at the National Institutes of Health (NIH). Working from an evolutionary biology perspective, she’s interested in how the parasite has changed over time.

PlasmoDb, a database of Plasmodium informatics resources, is a tool developed in part by the work of Distinguished Research Professor Jessica Kissinger, who became interested in malaria during her postdoctoral training at the National Institutes of Health.

“I see it as an arms race,” Kissinger said. “I want to understand what moves they have and can make.”

To understand the parasite, you must dive deep into its genetic code.

Kissinger paired her work in Plasmodium genomics with her interest in computing by helping create the database with information from the Plasmodium genome project completed in 2002. The Malaria Host-Pathogen Interaction Center, one of her projects at UGA, was a seven-year, multi-institutional effort funded, in part, by NIH to create data sets that could be used in systems biology of the host-pathogen interaction during the development of disease.

“Wouldn’t it be neat if, from the beginning of infection all the way to cure, you knew everything that was going on in the organism all the time?” Kissinger said, noting the project’s goal.

They generated terabytes of data that, along with data from the global research community, are publicly accessible and reusable through PlasmoDB and other resources.

Being part of a group that is studying so many different aspects of malaria helps put Kissinger’s research into perspective. Now, in addition to understanding the parasite, she also thinks about tools needed to facilitate research from peers.

High-tech solutions rely on basic research

David Peterson, professor of infectious diseases in the College of Veterinary Medicine, noted that low-tech solutions have mitigated malaria’s human costs. He acknowledged, however, that their long-term goals required more.

“We have to acknowledge that low-tech solutions, such as mosquito nets, have saved lives,” Peterson said. “But to develop the high-tech solutions that will one day end malaria, we need basic research.”

Pregnant women are particularly vulnerable to malaria because their existing immunity to malaria fails to protect them during pregnancy. Placental malaria often results in  premature birth and low birth weight.

Peterson is interested in a binding protein that allows the parasite to adhere to the placenta. While many P. falciparum parasites have only one gene copy that encodes the placental binding protein,  Peterson is investigating Plasmodiumisolates with two or more slightly different copies.

But why isn’t one copy enough?

David Peterson
Professor David Peterson of the College of Veterinary Medicine acknowledges the importance of low-tech solutions like mosquito nets but said to mitigate its effects required better understanding at the genetic level.

That is the primary question Peterson is focused on. He wants to understand how Plasmodium uses extra copies to evade the immune system, distinguishing the role of each requires tools that Vasant Muralidharan, associate professor of cellular biology, has.

Muralidharan’s interest began when he contracted malaria himself. Through access to good health care, he made a full recovery, but the pain he endured remained. He wanted to understand this parasite. Even more, he wanted to make an impact with research.

His graduate training focused on biophysics, but soon his interest in Plasmodium resurfaced. He discovered there was a lack of tools to study the parasite on a genetic level.

“It’s like a house of cards, and each card is a gene,” Muralidharan said. “You can remove one and see what happens—does the house fall or remain standing?”

This is an illustration of the life cycle of the parasites of the genus, Plasmodium, that are causal agents of malaria.(Illustration by CDC/ Alexander J. da Silva, PhD; Melanie Moser)

In the days before CRISPR/Cas9, there wasn’t a precise way to remove genes. Muralidharan is among the pioneers of gene-editing techniques in Plasmodium.

Like Peterson, Muralidharan focuses on proteins secreted by the parasite. He studies the largely unknown process that allows the parasite to invade a red blood cell (RBC), replicate and escape. The lack of tools was a major hindrance, so Muralidharan created new ones.

These tools have been used by Muralidharan’s CTEGD and CDC colleagues to see how drugs might fail. Muralidharan’s laboratory can create mutant Plasmodium parasites that become resistant to a particular drug, and genome sequence databases allow researchers to check if that mutant is already circulating in malaria endemic regions.

Vasant Quote

Building a research bridge to endemic regions

Plasmodium vivax is the predominant malaria parasite in Southeast Asia. It causes “relapsing malaria” during which some parasites go “dormant” after entering the liver instead of reproducing. This phase is a major obstacle for current treatments.

CTEGD Director Dennis Kyle, GRA Eminent Scholar Chair in Antiparasitic Drug Discovery and head of the Department of Cellular Biology, became fascinated with the Plasmodium parasite early in his career, spending time living in Thailand and working in refugee camps where malaria is prevalent.

Dennis Kyle
CTEGD Director Dennis Kyle was moved to follow through with his work as a researcher on a trip to a refugee camp in Thailand. Upon seeing the challenges residents faced, he thought perhaps he should have become a physician. Instead, a local leader impressed upon him the impact you could have in generating new treatments that could benefit everyone. (Photo by Andrew Davis Tucker/UGA)

“When I first got to the refugee camp and saw the situation people were living in, I questioned my decision to become a scientist in the lab instead of becoming a physician,” Kyle said, recalling a camp he worked in that housed about 1,300 kids between the ages of 2 and 15. “There was a guy who was a leader in the group who probably had no more than an early high school education. He said, ‘Look at what you can do—you might generate something that would benefit all of us. The physicians we have in the camp can only work on a few people at a time.’”

Kyle’s laboratory is looking to repurpose medications that have antimalarial properties, a safe way to reduce the development time from lab to clinical use. He’s optimistic we will see a drug treatment that eliminates vivax malaria.

“That’s where UGA is playing a major role,” he said. “The Gates Foundation funded us to develop tools to study the dormant parasite in the liver. And we’ve been successful.”

One of Kyle’s collaborators is Samarchith Kurup, assistant professor of cellular biology, who studies the human immune response to Plasmodium infection.

“We use mouse models to delve into the fundamental host-parasite interactions, which you cannot do practicallyin humans,” Kurup said. “Our understanding of these fundamental processes gives rise to newer and better vaccination approaches and drugs.”

Another important CTEGD addition is Chet Joyner, assistant professor of infectious diseases, whose work has helped make it easier to study dormant parasites stateside.

Like other Plasmodium researchers, Joyner became interested in parasites at an early age. During an undergraduate parasitology class, he discovered how little was known about P. vivax. He was already interested in how diseases develop, so for graduate school he focused on the liver stage of vivax malaria. However, it was a difficult task.

Samarchith Kurup is an assistant professor of cellular biology studying the human immune response to Plasmodium infection. (photo credit: Lauren Corcino)
Samarchith Kurup is an assistant professor of cellular biology studying the human immune response to Plasmodium infection. (photo credit: Lauren Corcino)
Chet Joyner
Assistant Professor Chet Joyner discovered how little was known about Plasmodium vivax as an undergraduate student.

“At the time, the technologies weren’t there,” Joyner said. “Dennis was working on his system, but it wasn’t on the scene yet. I changed from studying the parasite to studying the animal model to understand pathogenesis and immunology in humans.”

Joyner joined UGA after completing his postdoctoral training at Emory University, where he developed a non-mouse animal model to study vivax malaria.

“We have to go to [Thailand] where people are infected and collect blood samples and then feed mosquitoes these samples to do the necessary studies,” Kyle said. “That’s been very impactful. We’ve gotten a lot of data out of it, and now with Chet’s model it all can be done under one roof.”

Joyner wants to understand the human immune response with a focus on vaccine development. Building on Muralidharan’s and other researchers’ findings of how the parasite interacts with the RBCs, Joyner’s vaccine program targets a specific protein in the parasite that inhibits the development of immunity.

“My colleagues have shown that if you knock this protein out in the parasite, the immune response in mice is actually great, and we are now working together to evaluate this in non-mouse models.” Joyner said.

Joyner also has collaborated with Belen Cassera, professor of biochemistry, to screen drug compounds. Cassera’s training focused on metabolism to find drug targets. She is particularly interested in how a drug functions.

“If we understand how the drug works, it will help us predict potential side effects in humans,” Cassera said. “We can’t predict everything, but knowing how it works gives you some confidence in whether it will work in humans.”

Cassera is focused on finding drugs that will treat the more lethal Plasmodium falciparum, the predominant species in Africa, which is rapidly becoming resistant to current treatments. Her work is complementary to Kyle’s.

“They run certain assays for the liver-stage infection, and our lab benefits because we want to know if the drug we are developing is specific for the blood stage or can tackle all stages,” Cassera said.

M. Belen Cassera
Professor Belen Cassera is identifying drugs that will treat the lethal Plasmodium falciparum, a predominant species of the parasite in Africa that has become resistant to many current treatments.

Don’t forget the mosquito

“Malaria is a vector-borne disease transmitted by a mosquito. You need to tackle not only the parasite in the human but also stop its transmission,” Cassera said. “CTEGD is unique because we can study the whole life cycle, including the mosquito.”

Michael Strand, H.M. Pulliam Chair of Entomology in the College of Agricultural and Environmental Sciences and a National Academy of Sciences Fellow, is an expert on parasite-host interactions. Instead of the human host, he is interested in mosquitoes. Recent work indicates blood feeding behavior of mosquitoes strongly affects malaria parasite development while the gut microbiota of mosquitos could lead to new ways to control populations. Having the SporoCore insectory on campus aids his research.

Michael Strand is an expert on parasite-host interactions. His research focuses on mosquitoes and their effects on malaria parasite development.
Michael Strand is an expert on parasite-host interactions. His research focuses on mosquitoes and their effects on malaria parasite development.

Established in 2020, SporoCore, under the management of Ash Pathak, assistant research scientist in the Department of Infectious Diseases, provides both uninfected and Plasmodium-infected Anopheles stephensi mosquitoes to researchers at UGA and other institutions. Like Joyner’s animal model, the insectory allows for research to be done in the U.S. that would otherwise require field work in an endemic country.

Old-school interventions like mosquito nets, combined with new drug therapies, have reduced the number of malaria deaths, which declined over the last 30 years before rising slightly during the COVID-19 pandemic. Great strides have been made to control and treat malaria—but not enough. New tools, like the ones being developed at CTEGD, are needed to keep pushing malaria’s morbidity and mortality rates in the right direction.

“The hard part—what can’t be done easily with the tools we already have—is being done,” Kyle said. “We just need new tools, which is one of the things that our center is really a leader in.”

 

This story was first published at https://research.uga.edu/news/all-the-pieces-matter-uga-researchers-collaborate-to-solve-malaria-puzzle/

Chet Joyner receives $1.1 million grant to study malaria vaccine

RESEARCH WILL BE IN COLLABORATION WITH YALE UNIVERSITY

Chet Joyner, PhD, a faculty member in the Center for Vaccines and Immunology and the Center for Tropical and Emerging Diseases in the College of Veterinary Medicine (CVM) at the University of Georgia, is the recipient of a $1.1 million grant from Open Philanthropy to perform preclinical testing of a vaccine designed to prevent reinfection from malaria.

“A vaccine that lessens the impact of this disease will have incalculable value in terms of lives saved and the quality of life of those in the affected areas,” said Lisa K. Nolan, DVM, PhD, dean of the CVM. “We are proud of Dr. Joyner’s work and that he has chosen to do it in the College of Veterinary Medicine at the University of Georgia.”

Joyner is collaborating with Dr. Richard Bucala, MD, PhD, of Yale University to test the vaccine that targets Plasmodium-encoded Macrophage Migration Inhibitory Factor (pMIF), a protein secreted by Plasmodium falciparum, a pathogen that causes malaria.

The science team for Open Philanthropy, which recommended grants to Joyner and Bucala for the three-year study, believes that vaccinating against pMIF may provide an important boost to the efficacy of existing malaria vaccines, according to a statement on its website, openphilanthropy.org.

Open Philanthropy is a Silicon Valley-based nonprofit which aims to use its resources to help others as much as possible. They fund work in many areas, including global health.

Joyner, who was recruited from Emory University to join the CVM in January of 2020, said the college is uniquely positioned to test the efficacy of the vaccine developed by Bucala at Yale.

“We are a strong malaria group with unique infrastructure and facilities that can support this necessary research within the CVM,” Joyner said.

Immunity to malaria is acquired naturally after exposure, but the disease can be fatal to children younger than five and debilitating up to age 10 because malaria parasites disrupt the immune system’s response with their own proteins that mimic the human Macrophage Migration Inhibitory Factor (MIF).

Not only does the resulting illness cause children to miss school, but it also leads to long-term cognitive decline due to nutritional deficiencies. Parents miss work to care for children and the economic impacts compound.

According to the World Health Organization’s 2022 World Malaria report, an estimated 247 million cases of malaria occurred worldwide in 2021 and 619,000 people died, mostly children under the age of five in sub-Saharan Africa.

This story was originally published at https://vet.uga.edu/cvm-researcher-wins-1-1-million-grant-to-study-malaria-vaccine/

The CTEGD Cytometry Shared Resource Lab is growing!

CTEGD’s Cytometry Shared Resource Laboratory recently added a Malvern Panalytical NanoSight NS300 to their suite of cytometry instruments. This was a donation from the laboratory of Dr. Stephen Hajduk.

The NanoSight allows rapid analysis of the size distribution and concentration of all types of nanoparticles from 0.01 – 1 µm in diameter.  It is important to monitor and control the isolation and purification of extracellular vesicles (EVs) while conducting research into their function. NanoSight NTA (Nanoparticle Tracking Analysis (NTA) utilizes the properties of both light scattering and Brownian motion to provide quick and easy characterization of both the size and concentration of vesicles in aqueous buffers, giving confidence in the quality of the sample used in any downstream experiments.

Researchers across the UGA campus are investigating the role of EVs in T. brucei and N. fowleri infections, neural stem cell extracellular vesicle uptake and neutrophil uptake of exosomes isolated from cystic fibrosis sputum.

The NanoSight is the second instrument CSRL added in 2022 (see the Cytek Aurora Spectral Cytometer announcement) and increases the number of cytometry instruments available for CTEGD and the UGA research community use to 11.

The CSRL continues to provide access to state-of-the-art cytometry analyzers and sorters to researchers at the University of Georgia and across the scientific community. In addition to the instruments, the facility also provides expert advice and consultation for the design and analysis of flow experiments.