Technologies
Our laboratory is using two major strategies to discover new genes and pathways important for susceptibility to infectious disease. In a forward genetic approach we first identify inbred strains of mice that display substantial variation in infectious disease phenotypes. These are then used for quantitative trait loci (QTL) analysis to map resistance and susceptibility loci in the mouse genome. Strong QTLs are selected for positional cloning to identify genes underlying the variation in disease susceptibility.
In a second approach we use reverse genetics to test the putative involvement of genes in mediating disease. Based on a hypothesis about a putative gene function we use gene-targeting technology to inactivate or to modify a gene of interest. New transgenic mouse mutants are then generated and characterized for their immunocompetence in different in vivo infection models. Conditional (e.g. cell-specific) mouse mutagenesis is used to identify mechanisms involved in disease induction and progression.
Other technologies in the lab include the use of gene expression profiling. Here, we are using cDNA and exon arrays to gain a global understanding of gene expression and transcriptional regulation. Primary immune effector cells (for example macrophages) are isolated from mutant and wildtype mice and profiled for differences in gene expression. The functional relevance of genes identified to be differentially regulated is then tested in vivo.