Elucidating parasite specific requirements for chronic T. gondii infection in disparate tissues

RESEARCH PROJECT SUMMARY RPL: Robyn Kent, PhD Project Title: Elucidating parasite specific requirements for chronic T. gondii infection in disparate tissues More than one third of the world’s population is chronically infected with the parasite Toxoplasma gondii whose cysts remain in several host tissues lifelong. Current treatments are unable to clear the cysts. Instead, treatments control the active infection following cysts reactivation, leaving a pool of parasites with the potential for recurrent active infections. Recent work has identified T. gondii as a risk factor for dementia, schizophrenia and other neurological disorders and has also shown muscle weakness and cardiac arrhythmias can occur showing even without reactivation disease morbidity can occur. In cases where reactivation of the chronic infection occurs debilitating manifestations like toxoplasmic encephalitis and ocular disease can occur resulting in neurological disorders, vision loss and even death. The optimal treatment for T. gondii infection would therefore need to eliminate the cysts from all sites of infection, removing the cysts that cause morbidity and the pool of parasites that can reactivate. This project will use single cell RNA sequencing technology to characterize gene expression by parasites residing in different tissues to define the core transcriptome for chronically infecting parasites. We will use proteomics to identify common and tissue specific components of the cyst wall within which parasites reside, shielded from immune recognition. Finally, we will develop an assay to quantify the effect of specific cyst wall components on the longevity of the cysts in different tissues and determine how alterations to the cyst wall change persistence and the ability of the wall to shield parasites from the immune system. Combined these aims will provide the strongest candidates that can be targeted to reduce or eliminate cyst burden across the entire host after a chronic infection has been established and develop much needed assays to test these candidates.