USF College of Public Health’s Dr. Michael White, Distinguished USF Health Professor in the Department of Global Health, has been funded with more than $2.7 million to examine the developmental mechanisms responsible for tissue cyst formation of Toxoplasma gondii.
The five year R01 National Institute of Health grant will allow White and his team to work toward the development of a new drug or vaccine treatment to prevent diseases caused by Toxoplasma and its relatives from the Apicomplexa family, according to White.
The Centers for Disease Control and Prevention named Toxoplasma one of the five most neglected parasitic diseases.
“About one third of the world population is infected by Toxoplasma, and while the immune system of healthy people is able to control these infections, anyone with a compromised immune response is susceptible to a disease that can lead to death,” White said.
White said that even in healthy people, Toxoplasma, which prefers to infect the brain, could cause neurological complications including potential behavioral changes and other neurological complications.
“Once an individual is infected with Toxoplasma they are infected for the rest of their life,” he said. “A healthy immune system cannot eliminate the Toxoplasma cysts that will reside in the brain and muscle of infected people and no current treatment can eliminate this type of infection.”
Toxoplasma infection is contracted from contaminated meat products made from infected animals, water or soil contaminated by cats—which are the major carrier of the pathogen—and from mother to baby during pregnancy.
White said his research will focus on how Toxoplasma parasites switch from reproducing to dormancy in the tissue cyst, which he says is effectively invisible to the immune system and untreatable.
“The Toxoplasma biology that underlies chronic disease is a reversible transformation of the asexual replicating tachyzoite into the latent bradyzoite stage,” White said. “This critical developmental transition is accompanied by significant changes in gene expression controlled by poorly defined transcriptional mechanisms.”
White and his team hypothesize that there is a transcriptional network that directs the competing needs of tachyzoite growth against the development of the tissue cyst required for parasite transmission.
To understand the transcriptional network, White said, their research will focus on two aims: tachyzoite cell cycle repressors and how they control bradyzoite gene expression and how those mechanisms influence parasite development in animals.
“We have found by studying the function of AP2 [tachyzoite cell cycle repressors] factors in Toxoplasma that we can scramble them—delete specific AP2 genes or overexpress AP2 genes in the parasite—in ways that causes the parasite to missexpress its genes during an infection,” he said. “The consequence of this scrambling is very exciting as we have found in mouse models that this scrambling of AP2 factors helps the mouse immune system better fight the infection, and, importantly, help the immune system to prevent the cyst form that is responsible for life long infections.”
It was based on the success of these early studies, White said, that prompted the National Health Institutes to award him and his team this five-year grant in order to continue the studies on AP2 factors.
Students, staff and professionals involved in the grant research will also collaborate with the School of Medicine at Indiana University and University of California Riverside to come up with solutions to combat Toxoplasma gondii infections, such as through a vaccine based on scrambling the parasite’s transcriptional network, according to White.
“More than 50 million individuals in the U.S. are chronically infected with Toxoplasma gondii and thousands of healthy individuals develop eye disease leading to permanent vision loss,” White said. “Toxoplasma gondii infections continue to be a public health hazard for millions of individuals that contact this pathogen annually.”
Story by Anna Mayor, USF College of Public Health