TY - JOUR T1 - Identification of a master regulator of differentiation in <em>Toxoplasma</em> JF - bioRxiv DO - 10.1101/660753 SP - 660753 AU - Benjamin S. Waldman AU - Dominic Schwarz AU - Marc H. Wadsworth II AU - Jeroen P. Saeij AU - Alex K. Shalek AU - Sebastian Lourido Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/05/660753.abstract N2 - Toxoplasma gondii chronically infects a quarter of the world’s population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Chronic stages are established by differentiation of rapidly replicating tachyzoites into slow-growing bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. Despite its central role in infection, the molecular basis of chronic differentiation is not understood. Through Cas9-mediated genetic screening and single-cell transcriptional profiling, we identify and characterize a putative transcription factor (BFD1) as necessary and sufficient for differentiation. Translation of BFD1 appears to be stress regulated, and its constitutive expression elicits differentiation in the absence of stress. As a Myb-like factor, BFD1 provides a counterpoint to the ApiAP2 factors which dominate our current view of parasite gene regulation. Overall, BFD1 provides a genetic switch to study and control Toxoplasma differentiation, and will inform prevention and treatment of chronic infection. ER -