Saeij lab:Reprints

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Publications ($Denotes shared first author) Lim D, Gold DA, Julien L, Rosowski EE*, Niedelman W, Yaffe MB, Saeij JPJ. Structure of the Toxoplasma gondii ROP18 kinase domain reveals a second ligand binding pocket required for acute virulence. The Journal of Biological Chemistry. 2013. Accepted. Melo MB, Hassan MA, Nguyen QP, Butty V, Cordeiro C, Yang N, Rosowski EE, Julien L, McKell R, Darde M-L, Ajzenberg D, Fitzgerald K. Young LH, Saeij JPJ. Transcriptional analysis of murine macrophages infected with different Toxoplasma strains identifies novel regulation of host signaling pathways. PLoS Pathogens. 2013. Accepted. Niedelman W, Sprokholt JK, Clough B, Frickel EM, Saeij JPJ. Cell death of interferon-gamma stimulated human fibroblasts upon Toxoplasma gondii infection induces early parasite egress and limits parasite replication. Infection and Immunity. 2013. Accepted. Camejo A, Gold DA, Lu D, McFetridge K, Julien L, Yang N, Jensen KD, Saeij JPJ. Identification of three novel Toxoplasma gondii rhoptry proteins. International Journal for Parasitology. 2013. Accepted Yang N, Farrell A, Niedelman W, Melo MB, Lu D, Julien L, Marth GT, Gubbels MJ, Saeij JPJ. Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains. BMC Genomics. 14:467; 2013. “Highly accessed” Jensen KD, Hu K, Whitmarsh RJ, Hassan MA, Julien L, Lu D, Chen L, Hunter CA, Saeij JPJ. Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15. Infection and Immunity. 81(6):2156-67; 2013. ‘Article of significant interest’ selected by the editors, see Research Spotlight: Infection and Immunity, 81(6): 1859; 2013. Rosowski EE, Saeij JPJ. Toxoplasma gondii clonal strains all inhibit STAT1 transcriptional activity but polymorphic effectors differentially modulate IFNγ induced gene expression and STAT1 phosphorylation. PLoS One. 7(12):e51448; doi: 10.1371/journal.pone.0051448. 2012. Hassan MA, Melo MB, Haas B, Jensen KD, Saeij JPJ. De novo reconstruction of the Toxoplasma gondii transcriptome improves on the current genome annotation and reveals alternatively spliced transcripts and putative long non-coding RNAs. BMC Genomics. 13(1):696; 2012. “Highly accessed” Minot S$, Melo MB$, Li F, Lu D, Niedelman W, Levine SS, Saeij JPJ. Admixture and recombination among Toxoplasma gondii lineages explain global genome diversity. Proc Natl Acad Sci U S A. 2012 ;109(33):13458-6. In this manuscript we used a genome-wide SNP set from 26 different strains, representing global diversity, to show that most current isolates are recent recombinants and cannot be easily grouped into a limited number of haplogroups. A complex picture emerges in which some genomic regions have not been recently exchanged between any strains, and others recently spread from one strain to many others. Particularly, three haploblocks, on chrIa, XI, and XII, have recent common ancestry across multiple diverse lineages, perhaps suggesting that these regions may contain fitness loci. Our approach improves upon current methods because it analyzes recombination-defined haploblocks, building a more precise and comprehensive genealogy of Toxoplasma. We also put forward the hypothesis that the limited Toxoplasma diversity in North America might be a result of the late Pleistocene extinction (∼11,500 y ago), which eliminated ∼80% of large vertebrates in North America, including most Felidae members, causing a severe bottleneck and the demise of most North American Toxoplasma strains. Niedelman W, Gold DA, Rosowski EE, Sprokholt JK, Lim D, Farid Arenas A, Melo MB, Spooner E, Yaffe MB, Saeij JPJ. The Rhoptry Proteins ROP18 and ROP5 Mediate Toxoplasma gondii Evasion of the Murine, But Not the Human, Interferon-Gamma Response. PLoS Pathog. 2012 Jun;8(6):e1002784. Lim DC, Cooke BM, Doerig C, Saeij JPJ. Toxoplasma and Plasmodium protein kinases: roles in invasion and host cell remodelling. Int J Parasitol. 2012 Jan;42(1):21-32. Melo MB, Jensen KDC, Saeij JPJ. Toxoplasma gondii effectors are master regulators of the inflammatory response. Trends in Parasitology. 2011 Nov;27(11):487-95. Virreira-Winter S, Niedelman W, Jensen KD, Rosowski RE, Julien L, Spooner E, Caradonna K, Burleigh BA, Saeij JPJ, Ploegh HL, Frickel E. Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS One. 2011;6(9):e24434. Jensen KDC, Wang Y, Wojno ED, Shastri AJ, Hu K, Cornel L, Boedec E, Ong Y, Chien Y, Hunter CA, Boothroyd JC, Saeij JPJ. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. Cell Host & Microbe 9(6):472-83; 2011. Highlighted in: Macrophages as a battleground for Toxoplasma pathogenesis. Cell Host Microbe 9(6):445-7; 2011. MIT news: Biologists shed light on a puzzling parasite Reese ML, Zeiner GM, Saeij JP, Boothroyd JC, Boyle JP. Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. PNAS 108(23):9625-30; 2011. Selected by Faculty of 1000: Factor 6. Rosowski E$, Lu D$, Julien L, Rodda L, Gaiser R, Kirk J, Saeij JPJ. Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma dense granule protein. J Exp Med 208(1):195-212; 2011. Selected by Faculty of 1000: Factor 6. Highlighted in: It takes II to induce NF-κB. Nature Reviews Microbiology 9, 147, 2011. MIT news: On the trail of a stealthy parasite Blader IJ, Saeij JPJ. Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence. APMIS. 117(5-6):458-76; 2009. Boyle JP, Saeij JP, Harada SY, Ajioka JW, Boothroyd JC. Expression quantitative trait locus mapping of toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression. Eukaryot Cell. 7(8):1403-14; 2008. In this paper we used quantitative genetics to identify Toxoplasma genes that are expressed in a strain-specific manner. For one of these genes, the rhoptry kinase ROP18, it is known that it is the difference in expression level between strains that causes differences in virulence. The biological consequences of expression level differences of the other genes is currently unknown. Saeij JPJ, Arrizabalaga G, Boothroyd JC. A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence. Infection and Immunity 76(6): 2402-2410; 2008. Here we removed for the first time four adjacent genes using double homologous recombination. These are surface antigens that are expressed in bradyzoites but not in tachyzoites. Interestingly, parasites without these surface antigens are less able to persist in the brain of mice. We also show that using a bradyzoite specific promoter driving luciferase expression can show stage conversion in real time in life mice in vivo (using an IVIS imaging system). Boyle JP, Saeij JPJ, Boothroyd Inconsistent dissemination patterns of Toxoplasma gondii following oral infection. Experimental Parasitology 116(3):302-305; 2007. Saeij JPJ$, Coller S$, Boyle JP, Jerome ME, White MW, Boothroyd JC. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445(7125): 324-327; 2007. Selected by Faculty of 1000: Factor 17. Highlighted in: Toxo researchers spot the difference. Nature Reviews Microbiology 5, 86, 2007. Saeij JPJ$, Boyle JP$, Coller SC, Taylor S, Sibley LD, Brooke-Powell ET, Ajioka JW, Boothroyd JC. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314(5806):1780-1783; 2006. Selected by Faculty of 1000: Factor 14. Highlighted in: Toxo researchers spot the difference. Nature Reviews Microbiology 5, 86, 2007; Nature Immunology 8, 129 (2007). Boyle, JP, Rajasekar B, Saeij JPJ, Ajioka JW, Berriman M, Paulsen I, Roos DS, Sibley D, White M, Boothroyd JC. Just one cross appears capable of dramatically altering the population biology of a eukaryotic pathogen like Toxoplasma gondii. PNAS 103(27): 10514-10519; 2006. Selected by Faculty of 1000: Factor 6. Boyle JP, Saeij JPJ, Cleary MD, Boothroyd JC. Analysis of gene expression during development: lessons from the apicomplexa. Microbes and Infection 8(6): 1623-1630; 2006. Saeij JPJ$, Boyle JP$, Grigg ME, Arrizabalaga G, Boothroyd JC. Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains. Infection and Immunity. 73(2): 695-702; 2005. Selected by Faculty of 1000: Factor 6. Saeij JPJ, Boyle JP, Boothroyd JC. Differences among the three major strains of Toxoplasma gondii and their specific interactions with the infected host. Trends in Parasitology. 21(10): 476-81; 2005.