A screen for dominant negative genes will be used to identify targets and pathways in Candida albicans. The genes and pathways identified will be developed as new antifungal targets. An expression vector system suitable for screening libraries in C. albicans has been devised. Phase I of this project includes final construction and optimization of the expression vector and construction of cDNA libraries capable of identifying dormant negative mutants. Preliminary screening will begin in Phase I. Phase II of the project will entail identifying essential genes and processes by dominant negative mutagenesis and to develop screens for new antifungals based on these essential genes. The method proposed for identifying essential genes is ideal for C. albicans, a diploid human pathogen not normally amenable to genetic analysis, and can be automated. PROPOSED COMMERCIAL APPLICATIONS: Elitra is creating a unique relational database of both targets and drug screens for major gene/protein targets across multiple pathogens. This database will markedly enhance the ability of Elitra and its corporate partners to make informed decisions about which novel targets to pursue. Elitra has built a unique, ultra rapid Gene-to-Screen technology platform that will allow miniaturized drug screens to be developed for any validated target in its proprietary database within 2-3 weeks. Screening for new antibiotics begun with the in-house chemical screening library of 250,000 plus compounds.