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Identification of a master regulator of differentiation in Toxoplasma

Benjamin S. Waldman, Dominic Schwarz, Marc H. Wadsworth II, Jeroen P. Saeij, Alex K. Shalek, Sebastian Lourido
doi: https://doi.org/10.1101/660753
Benjamin S. Waldman
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
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Dominic Schwarz
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
3Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
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Marc H. Wadsworth II
4Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
5Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
6Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02319, USA
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Jeroen P. Saeij
7Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA
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Alex K. Shalek
4Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
5Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
6Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02319, USA
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Sebastian Lourido
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
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  • For correspondence: lourido@wi.mit.edu
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SUMMARY

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 05, 2019.
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Identification of a master regulator of differentiation in Toxoplasma
Benjamin S. Waldman, Dominic Schwarz, Marc H. Wadsworth II, Jeroen P. Saeij, Alex K. Shalek, Sebastian Lourido
bioRxiv 660753; doi: https://doi.org/10.1101/660753
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Identification of a master regulator of differentiation in Toxoplasma
Benjamin S. Waldman, Dominic Schwarz, Marc H. Wadsworth II, Jeroen P. Saeij, Alex K. Shalek, Sebastian Lourido
bioRxiv 660753; doi: https://doi.org/10.1101/660753

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