Sarah Sokol Borrelli, Boyle Lab
Elucidating the mechanisms driving stage conversion in Toxoplasma gondii
Toxoplasma gondii infects approximately one third of the world’s population. This parasite resides in its host, presumably for life, in the form of incurable tissue cysts. Infection with T. gondii is typically asymptomatic, but it can cause severe disease in immunocompromised individuals because its tissue cysts can reactive into actively replicating life stages. The formation and reactivation of tissue cysts underlies T. gondii’s uniquely flexible life cycle and is critical for its transmission. Despite the importance of tissue cysts, the mechanisms regulating their formation have yet to be fully elucidated. My goal is to identify the genes driving tissue cyst formation in T. gondii by conducting interspecies comparisons with its closest extant relative, Hammondia hammondi. H. hammondi exhibits critical differences in life stage progression and gene expression despite possessing extensive genomic similarity with T. gondii. These life stage progression differences include the timing and efficiency of tissue cyst formation along with a differential response to tissue cyst inducing stressors. To identify genes driving cystogenesis, I have conducted transcriptional profiling during critical developmental timepoints for both species and in response to tissue cyst inducing stressors allowing for the identification of 19 candidate genes for further investigation. I have genetically manipulated 4 of these genes in T. gondii and identified one unique gene, TgME49_311100, that significantly reduced tissue cyst formation and dramatically altered T. gondii’s transcriptional stress response upon disruption. In the future, I will characterize TgME49_311100 to determine its functional role in tissue cyst formation in T. gondii and H. hammondi.
Friday, April 24, 2020
12PM