Sequence-based Analysis of Parasite Diversity and Host Interactions for Plasmodium and Toxoplasma

Summary

Human parasites cause some of the most important infectious diseases worldwide (e.g. malaria), and infect millions of individuals each year within the US (e.g. toxoplasma). Despite the availability of several reference sequences for parasite genomes, we have a very limited understanding of the mechanisms by which parasites infect and persist within their human hosts. This project will exploit current high-throughput sequencing technologies and bioinformatics techniques to provide novel insights to parasitic infectious diseases.

Our broad objectives are to understand pathogen diversity, evolution, and their interactions with the human host and associated microbiota. These objectives are addressed through three specific aims, applied to two apicomplexan species of major concern in the US (Toxoplasma gondii) and worldwide (Plasmodium falciparum). Particular emphasis is given to the study of host-parasite interactions, through the sequencing of DNA and RNA from both the parasites and their human hosts.

Specific Aim 1 will apply sequence-based analysis of natural and mutant T. gondii strains to determine the worldwide genomic complexity for this species, and permit predictions of host and parasite genes that are involved with specific infection and replication phenotypes. Specific Aim 2 will apply sequence-based analysis of host-parasite interactions during experimental and natural P. falciparum infections of humans, to identify the genomic and transcriptomic basis of immune profiles that are associated with protection from the symptoms of malaria. Specific Aim 3 will characterize the composition of bacterial and eukaryotic species in the gut microbiome during the course of infections with P. falciparum to determine the reciprocal effects on microbiome composition and disease progression.

Each of the specific aims employs innovative experimental designs and technology development, and is most appropriate for a large-scale program that can generate and process extensive volumes of sequence data. The project addresses important problems that apply to the specific species under study, and to the larger field of parasitic infectious disease. By achieving the objectives of this project, we will provide a model for how future projects could be accomplished for many other pathogens of interest. Please contact gcid@jcvi.org if you have any questions.

Project Director:

Dr. Hernan Lorenzi Profile Dr. Hernan Lorenzi, Project Director, Assistant Professor

Collaborators:

Dr. John Boothroyd Profile Dr. John Boothroyd, Stanford University Sch. Med. Collaborator, Toxoplasma Dr. David Bzik Profile Dr. David J. Bzik, Professor of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Toxoplasma
Dr. Peter Crompton Profile Dr. Peter Crompton, NIAID, NIH Collaborator, Plasmodium Dr. Marie-Laure Darde Profile Dr. Marie-Laure Darde, INSERM Collaborator, Toxoplasma
Dr. Marc-Jan Gubbels Profile Dr. Marc-Jan Gubbels, associate professor of biology, Boston College, Toxoplasma Dr. Rima McLeod Profile Dr. Rima McLeod, Professor of Ophthalmology Pediatrics Medical Director, Toxoplasmosis Center, University of Chicago Collaborator, Toxoplasma
Dr. Jeroen Saeij Profile Dr. Jeroen Saeij, Massachusetts Institute of Technology, Toxoplasma Dr. Robert Sauerwein Profile Dr. Robert Sauerwein, Radboud University Nijmegen, Plasmodium
Dr. Gereon Schares Profile Dr. Gereon Schares, Friedrich-Loeffler Institute Collaborator, Toxoplasma Dr. L David Sibley Profile Dr. L David Sibley, Professor, Molecular Microbiology, Washington University Collaborator, Toxoplasma
Dr. Chunlei Su Profile Dr. Chunlei Su, Associate Professor, The University of Tennessee, Toxoplasma Collaborator

Citations

All Publications that use data generated and/or are supported by the Sequencing Center at JCVI should acknowledge the sponsor as below:

"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."