Editing BioMicroCenter:Research (section)

=== Genomics of Toxoplasma gondii - [http://web.mit.edu/biology/www/facultyareas/facresearch/saeij.html SAEIJ LAB] - [http://web.mit.edu/biology Biology]===
The overall goal of the Saeij lab is to understand the molecular basis for individual differences in outcome of infection. We believe that these differences are either due to host differences in resistance/susceptibility to infection or to genetic differences in the pathogen that causes the infection. As a model we use infection with the obligate intracellular pathogen Toxoplasma gondii. Toxoplasma can infect all warm-blooded animals and a third of the world’s population is estimated to be infected. There are many different Toxoplasma strains that differ hugely in virulence in both mice and humans. Mouse and rat strain differences in resistance/susceptibility to Toxoplasma have also been described.<BR><BR>
To characterize Toxoplasma genetic diversity we sequenced (Illumina HiSeq), with the help of the BioMicro Center, the whole genome of 10 Toxoplasma strains and the transcriptome of 32 different strains, representing global diversity. This data allowed us to construct the first Toxoplasma haplotype map and to propose a new model explaining current global diversity. The results were published in PNAS (Minot et al, 2012). We also determined the transcriptome of murine macrophages infected with these 32 different strains. This approach allowed us to correlate genotype with phenotype and have led to the identification of Toxoplasma loci and genes that affect fitness, clonality, virulence and modulation of host signaling pathways. Some of these results were published in PLoS Pathogens (Niedelman et al, 2012).<BR><BR>
To determine mouse genetic differences in resistance/susceptibility to Toxoplasma we determined the transcriptome and toxoplasmacidal activity of naïve or IFNγ+TNF-stimulated macrophages isolated from 29 recombinant inbred mice, derived from A/J (Toxoplasma resistant) and C57BL/6 (susceptible) mice. We then identified mouse genomic loci affecting mouse gene expression and toxoplasmacidal activity using quantitative trait locus (QTL) analysis. We are now using genetic approaches to confirm mouse candidate genes involved in macrophage differences in Toxoplasma killing ability. The results of this study have helped us secure four years of grant support from the New England Regional Center of Excellence Biodefense and Emerging Infectious Diseases.<BE><BE>
We have received excellent help from the BioMicro Center at every step of these analyses, their many suggestions on how to analyze the data have been instrumental in getting high quality data.<BR><BR>