PAST PROJECT

Sequence-Based Analysis of Natural and Mutant Toxoplasma Gondii Strains, and Their Interactions with Host Cells

There is limited understanding at the molecular level of many aspects of T. gondii biology, such as its pathogenicity, transmission, tropism and manipulation of host cell functions. We are addressing this gap by sequence-based analysis of both natural and mutant T. gondii strains that display characteristic phenotypes. We are currently analyzing the whole genome sequences of wild-type T. gondii strains that represent new pockets of diversity, or that were isolated from geographic regions where little is known about the composition or structure of T. gondii populations. These genome sequences are being compared to each other, and to related non-pathogenic species. In addition, we are analyzing the genomes and transcriptomes from a wide range of mutant parasites that exhibit characteristic phenotypes related to infectivity, virulence and immunological evasion. Our overarching hypothesis is that comparative genomic and transcriptomic analyses will reveal relevant associations between phenotypes of medical relevance and specific genes or gene networks (in both T. gondii cells and host cells). The knowledge generated by this project is supporting a variety of functional studies involving mechanisms of parasite infection, diagnostics and parasite surveillance, development of antiparasitic drugs and vaccines, host immunity, and control of infection. Please contact us if you have any questions.

Publications

PLoS pathogens. 2018-01-22; 14.1: e1006828.
Identification of a novel protein complex essential for effector translocation across the parasitophorous vacuole membrane of Toxoplasma gondii
Marino ND, Panas MW, Franco M, Theisen TC, Naor A, Rastogi S, Buchholz KR, Lorenzi HA, Boothroyd JC
PMID: 29357375
Genome announcements. 2017-11-16; 5.46:
Draft Genome Sequence and Annotation of the Apicomplexan Parasite
Schares G, Venepally P, Lorenzi HA
PMID: 29146849
Scientific reports. 2017-09-13; 7.1: 11496.
Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
NgĂ´ HM, Zhou Y, Lorenzi H, Wang K, Kim TK, Zhou Y, El Bissati K, Mui E, Fraczek L, Rajagopala SV, Roberts CW, Henriquez FL, Montpetit A, Blackwell JM, Jamieson SE, Wheeler K, Begeman IJ, Naranjo-Galvis C, Alliey-Rodriguez N, Davis RG, Soroceanu L, Cobbs C, Steindler DA, Boyer K, Noble AG, Swisher CN, Heydemann PT, Rabiah P, Withers S, Soteropoulos P, Hood L, McLeod R
PMID: 28904337
NPJ vaccines. 2017-09-05; 2.24.
Protein nanovaccine confers robust immunity against Toxoplasma
El Bissati K, Zhou Y, Paulillo SM, Raman SK, Karch CP, Roberts CW, Lanar DE, Reed S, Fox C, Carter D, Alexander J, Sette A, Sidney J, Lorenzi H, Begeman IJ, Burkhard P, McLeod R
PMID: 29263879
eLife. 2017-08-18; 6.
Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens
Amberg-Johnson K, Hari SB, Ganesan SM, Lorenzi HA, Sauer RT, Niles JC, Yeh E
PMID: 28826494
Scientific reports. 2016-08-10; 6.31291.
Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria
Tran TM, Jones MB, Ongoiba A, Bijker EM, Schats R, Venepally P, Skinner J, Doumbo S, Quinten E, Visser LG, Whalen E, Presnell S, O'Connell EM, Kayentao K, Doumbo OK, Chaussabel D, Lorenzi H, Nutman TB, Ottenhoff TH, Haks MC, Traore B, Kirkness EF, Sauerwein RW, Crompton PD
PMID: 27506615
Scientific reports. 2016-07-14; 6.29179.
New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections
McPhillie M, Zhou Y, El Bissati K, Dubey J, Lorenzi H, Capper M, Lukens AK, Hickman M, Muench S, Verma SK, Weber CR, Wheeler K, Gordon J, Sanders J, Moulton H, Wang K, Kim TK, He Y, Santos T, Woods S, Lee P, Donkin D, Kim E, Fraczek L, Lykins J, Esaa F, Alibana-Clouser F, Dovgin S, Weiss L, Brasseur G, Wirth D, Kent M, Hood L, Meunieur B, Roberts CW, Hasnain SS, Antonyuk SV, Fishwick C, McLeod R
PMID: 27412848

Funding

Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number U19AI110819. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Collaborators

John Boothroyd
Stanford University Sch. Med.

David J. Bzik, PhD
Geisel School of Medicine at Dartmouth

Peter Crompton, MD, MPH
NIAID, NIH

Marie-Laure Darde
INSERM

Marc-Jan Gubbels, PhD
Boston College

Rima McLeod, MD
Toxoplasmosis Center, University of Chicago

Jeroen Saeij
Massachusetts Institute of Technology

Robert Sauerwein MD PhD
Radboud University Nijmegen

Gereon Schares
Friedrich-Loeffler Institute

David Sibley, PhD
Washington University

Chunlei Su, Associate Professor
The University of Tennessee

Solange Gennari, Associate Professor
University of Sao Paulo, Brazil

Jitender Dubey, Associate Professor
US Department of Agriculture

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