Abstract The goals of the Model Organisms Core are to carry out the biohazardous research projects that are proposed in the Projects 1-4 and within the Core itself, and to maintain the culture collection of different strains of both species of Coccidioides. This Core has two aims. One is to carry out all the activities and experiments proposed in the projects that involve live, virulent Coccidioides species, Coccidioides immitis and Coccidioides posadasii, as they are classified as BSL3 pathogens. The other aim of the Core C is to utilize new methods to make targeted mutations in conserved genes in both species of Coccidioides, and to test the mutants for their ability to grow on media and in mice. The BSL3 facility will enable testing new hypotheses from Projects 1, 2, & 3 in mice, and to generate new hypotheses about immune responses from the results of mouse experiments proposed in Aim 1 to inform Project 3. The proposed studies in Aim 2 are directly related to Project 4 and will also shed light on the fungal genes that contribute to virulence, which may be new targets for therapeutics, and to identify host genes and response pathways that control immune responses to Coccidioides infection, which may reveal new therapeutic targets for biological agents.