Toxoplasma gondii and the study of host-parasite interactions

Intracellular pathogens are a major cause of mortality and morbidity in humans. Many intracellular pathogens secrete proteins that manipulate host cells to create the niche in which the pathogen can replicate. In turn, host cells have intricate mechanisms to detect and combat invading pathogens. As a consequence pathogens and their hosts co-evolve, leading to variation in both host and pathogen genomes and to the emergence of differences in parasite virulence and host resistance. Compared to bacteria and viruses, relatively little is known about how more complex eukaryotic pathogens co-evolve with and manipulate their hosts.

We are interested in susceptibility to infection which is likely caused by a complex interplay between host and parasite. We study host-parasite interactions between the obligate intracellular eukaryotic parasite Toxoplasma gondii and its hosts. Toxoplasma can infect virtually any cell and causes life-long chronic infections (toxoplasmosis) in most warm-blooded animals. It is estimated that 30% of humans are infected with Toxoplasma. Although most infected individuals are asymptomatic, Toxoplasma can cause severe disease in immunosuppressed individuals and fetuses and also causes ocular disease in otherwise healthy people. Toxoplasma virulence differs, often quite dramatically, depending on the infecting strain and the host. The focus of the Saeij laboratory over the last years has been to identify genes of Toxoplasma that modulate the host cell and/or determine virulence, host genes and pathways that determine resistance/susceptibility, and to characterize their specific interactions. To achieve this we use a combination of genetics, genomics, biochemistry, microscopy, immunology and computational tools.

For more information on what we do please visit our research pages


Toxoplasma gondii in the media

Latest News

  • [Jan, 2016] David Arranz Solis starts as a postdoctoral fellow in the Saeij lab, welcome David!
  • [Feb, 2016] Tatiana Paredes Santos starts as a postdoctoral fellow in the Saeij lab, welcome Tatiana!
  • [Jan, 2016] Shruthi Krishnamurthy starts as a postdoctoral fellow in the Saeij lab, welcome Shruthi!
  • [Jan, 2016] Lamba Sangare starts as a postdoctoral fellow in the Saeij lab, welcome Lamba!
  • [Nov, 2015] Debanjan Mukhopadhyay starts as a postdoctoral fellow in the Saeij lab, welcome Debanjan!
  • [Nov, 2015] Yifan Wang starts as a postdoctoral fellow in the Saeij lab, welcome Yifan!
  • [Oct, 2015] Kimberly Cirelli successfully defends her thesis, she will start as a postdoc in Shane Crotty's lab at the La Jolla Institute for Allergy and Immunology.
  • [Sep, 2015] The Saeij lab is now officially located at UC Davis
  • [June, 2015] Dan Gold and Kimberly Cirelli both won a best oral presentation award at the international toxoplasmosis meeting
  • [May, 2015] Kimberly Cirelli wins a AAI Trainee Poster Award
  • [May 2015] Dan Gold's paper describing the molecular basis for the pores in the Toxoplasma parasitophorous vacuole membrane that mediate the passive diffusion of small molecules into the vacuole is published in Cell Host & Microbe. Read an MIT news article describing this research.
  • [May, 2015] The NIH funds our R21 proposal to identify novel peptides that can be used to determine the exact strain people infected with Toxoplasma are infected with.
  • [Apr, 2015] The NIH funds our R01 renewal on characterizing the Toxoplasma proteins involved in the modulation of the host cell. We published 24 papers during the first five years of funding!
  • [Apr, 2015] The Saeij lab is looking for 4 new postdoctoral fellows. Go to Opportunities for information on how to apply.
  • [Apr, 2015] On September 1st, 2015, The Saeij lab is going to move to the Department of Pathology, Microbiology and Immunology at the School of Veterinary Medicine at the Univesity of California Davis. We are excited that we will now also be able to investigate the Toxoplasma sexual cycle in cats.
  • [Feb, 2015] Ana Camejo starts her new job as the editor for Trends in Parasitology.
  • [Feb, 2015] Kirk Jensen's and Ana Camejo's paper showing that Toxoplasma gondii Superinfection and Virulence during Secondary Infection Correlate with the Exact ROP5/ROP18 Allelic Combination is published in Mbio.
  • [Dec, 2014] The NIH funds our R21 on characterizing the Toxoplasma proteins involved in forming the pore in the parasitophorous vacuole membrane that mediates passive transport of small molecules.
  • [Nov, 2014] Musa Hassan's review on incorporating alternative splicing and mRNA editing into the genetic analysis of complex traits is published.
  • [Sep, 2014] Ninghan Yang successfully defends her thesis, she will continue her research career in Antonia Bertoletti's lab at the Duke-NUS Graduate Medical School.
  • [Sep, 2014] Kirk Jensen starts as an assistant professor in UC Merced
  • [May, 2014] Jeroen Saeij awarded tenure at MIT
  • [Sep, 2014] Musa Hassan continues his Wellcome trus-MIT fellowship in the lab of Prof. Markus Meissner at the Wellcome Trust Centre for Molecular Parasitology in Glasgow
  • [May, 2014] Microbiology graduate student Ben Waldman joins the Saeij lab
  • [Feb, 2014] Emily Rosowski's paper on the mechanisms by which Toxoplasma inhibits STAT1 activity published in Infection and Immunity. Read the paper
  • [Jan, 2014] Eleni Konstantinou starts as a research fellow in the Saeij lab
  • [Jan 6, 2014] Kimberly Cirelli's paper on the dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii accepted in mBio. Read the paper
  • [Dec 22, 2013] Kimberly Cirelli's paper on the genetic basis for rat strain differences in macrophage pyroptosis upon Toxoplasma infection accepted in PLoS Pathogens.
  • [Dec 19, 2013] Mariane Melo's paper on transcriptome analysis of macrophages infected with 29 different Toxoplasma strains published in PLoS Pathogens. (Read the paper). *News Coverage: MIT news
  • [Dec, 2013] Wendy Niedelman's paper on the mechanism by which gamma interferon-stimulated human fibroblasts inhibit Toxoplasma growth published in Infection and Immunity. (Read the paper).
  • [Nov 29, 2013] Dan Lim's paper on the crystal structure of the ROP18 kinase published in The Journal of biological chemistry. (Read the paper).
  • [Nov 13, 2013] Musa Hassan's paper on the genetic basis for individual differences in RNA editing accepted in Genome Research.
  • [Sep, 2013] Ana Camejo's paper on the discovery of novel rhoptry proteins accepted in The International Journal for Parasitology.
  • [July 1o, 2013] Ninghan Yang's paper on the genetic basis for phenotypic differences between type I strains published in BMC Genomics. (Read the paper).
  • [June, 2013] Kirk Jensen's paper on the role of ROP16 and GRA15 on the modulation of intestinal inflammation published in Infection and Immunity. (Read the paper).
  • [June, 2013] Daniel Gold wins The “Elsevier Investigator Award for best talk” at the 12th International Congress on toxoplasmosis at St. Catherine’s College, Oxford University in England.
  • [May 19, 2013] Jeroen Saeij gives the Division AA Lecture at the ASM 113th general meeting "Susceptibility to Infection: A Complex Interplay between Host and Parasite Genotypes". *News coverage: ASM Microbe Magazine.

  • Latest Research

    40. Transcriptional analysis of murine macrophages infected with different Toxoplasma strains identifies novel regulation of host signaling pathways.

    Melo MB, Nguyen QP, Cordeiro C, Hassan MA, Yang N*, McKell R*, Rosowski EE*, Julien L, Butty V, Darde M-L, Ajzenberg D, Fitzgerald K. Young LH, Saeij JP. PLoS Pathogens. 9(12):e1003779; 2013. PDF. Although Toxoplasma normally causes a lifelong asymtomatic infection cases of severe disease in otherwise healthy individuals have been observed. These cases are usually a result of infection with less common atypical strains. Factors associated with virulence in the atypical strains are not well under
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    39. Structure of the Toxoplasma gondii ROP18 Kinase Domain Reveals a Second Ligand Binding Pocket Required for Acute Virulence.

    Lim D, Gold DA, Julien L, Rosowski EE*, Niedelman W*, Yaffe MB#, Saeij JP#. The Journal of Biological Chemistry. 288(48):34968-80; 2013. PDF To further our understanding of ROP18 regulation and function, we have solved the crystal structure of its kinase domain and identified features important for virulence in mice. Our structure is the first determined for a catalytically active rhoptry kinase and builds on data from previously published crystal structures of the pseudokinase domains of ROP2 (
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    38. Cell Death of Gamma Interferon-Stimulated Human Fibroblasts upon Toxoplasma gondii Infection Induces Early Parasite Egress and Limits Parasite Replication.

    Niedelman W*, Sprokholt JK, Clough B, Frickel EM, Saeij JP. Infection and Immunity. Sep 16; 81(12):4341-9; 2013. PDF. Toxoplasma is a tryptophan auxotroph and IFNg-induced expression of IDO results in the degradation of tryptophan and the inhibition of Toxoplasma growth in many human cells. We found that IFNg-stimulated primary human foreskin fibroblasts (HFFs) strongly inhibit the growth of all Toxoplasma strains but this growth inhibition is largely independent of tryptophan. Instead IFNg-stim
    Read More

    37. Identification of three novel Toxoplasma gondii rhoptry proteins.

    Camejo A, Gold DA, Lu D*, McFetridge K, Julien L, Yang N*, Jensen KD, Saeij JP. International Journal for Parasitology. S0020-7519(13)00222-1; 2013. [Epub ahead of print]. PDF.
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    36. Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains.

     Yang N*, Farrell A, Niedelman W*, Melo MB, Lu D*, Julien L, Marth GT, Gubbels MJ, Saeij JP. BMC Genomics. 14:467; 2013. PDF The most used Toxoplasma strain is the type I RH strain, originally isolated in 1939 by Albert Sabin (famous for developing the oral polio vaccine) from a boy that died from toxoplasmic encephalitis and later cloned by Elmer Pfefferkorn in 1977. This RH strain has been passaged in vitro for a very long time (RH-ERP or RH88) and differs significantly in growth characteristi
    Read More

    35. Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15.

     Jensen KD, Hu K, Whitmarsh RJ, Hassan MA, Julien L, Lu D*, Chen L, Hunter CA, Saeij JP. Infection and Immunity. 81(6):2156-67; 2013. PDF ‘Article of significant interest’ selected by the editors, see Research Spotlight: Infection and Immunity, 81(6): 1859; 2013. Why do certain Toxoplasma strain cause a lethal inflammatory response after oral infection?
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    32. Admixture and recombination among Toxoplasma gondii lineages explain global genome diversity.

    Minot S$, Melo MB$, Li F, Lu D*, Niedelman W*, Levine SS, Saeij JP. PNAS. 14;109(33):13458-63; 2012. PDF Not so long ago people thought that Toxoplasma population structure was largely clonal and consisted of only a couple of strains that propagated mainly asexually. This was partially due because most Toxoplasma isolates were from Europe and North America and often only a couple of genetic markers were used to genotype strains. Sampling from other continents, especially South America, and the u
    Read More

    31. The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response.

    31. Niedelman W*, Gold DA, Rosowski EE*, Sprokholt J, Lim D, Farid A, Melo MB, Spooner E, Yaffe MB, Saeij JP. PLoS Pathogens. 8(6):e1002784; 2012. PDF
    Read More

    29. Toxoplasma and Plasmodium protein kinases: roles in invasion and host cell remodelling.

    Lim DC, Cooke BM, Doerig C, Saeij JP. International Journal for Parasitology. 42(1):21-32; 2012. [Review article] PDF
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    28. Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it.

    Virreira-Winter S, Niedelman W*, Jensen KD, Rosowski EE*, Julien L, Spooner E, Caradonna K, Burleigh BA, Saeij JP, Ploegh HL, Frickel E. PLoS One. 6(9):e24434; 2011. PDF
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    27. Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence.

    Reese ML, Zeiner GM, Saeij JP, Boothroyd JC, Boyle JP. PNAS 108(23):9625-30; 2011. PDF Selected by Faculty of 1000.
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    26. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.

    Jensen KD, Wang Y, Tait ED, Shastri AJ, Hu K, Cornel L, Boedec E, Ong Y, Chien Y, Hunter CA, Boothroyd JC, Saeij JP. Cell Host & Microbe 9(6):472-83; 2011. PDF Highlighted in: Macrophages as a battleground for Toxoplasma pathogenesis. Cell Host & Microbe 9(6):445-7; 2011.
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    24. Strain-specific activation of the NF-kB pathway by GRA15, a novel Toxoplasma gondii dense granule protein

    Rosowski EE$*, Lu D$*, Julien L, Rodda L, Gaiser R, Jensen KD, Saeij JP. Journal of Experimental Medicine 208(1):195-212; 2011. PDF Selected by Faculty of 1000. Highlighted in: It takes II to induce NF-κB. Nature Reviews Microbiology 9, 147, 2011.  
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    23. Communication between Toxoplasma gondii and its host: impact on parasite growth, development, immune evasion, and virulence.

     Blader IJ, Saeij JP. APMIS (acta pathologica, microbiologica, et immunologica Scandinavica). 117(5-6):458-76; 2009. [Review article] PDF
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