A two-step, scalable method is described for identifying the cellularfunction(s) of one or more genes of unknown function, and for identifyingmodulators or the gene(s). The method uses the reversal or alteration of aphenotype created by the expression of the heterologous gene, e.g., a humangene, to identify modulators of that gene's activity. That modulator is thenused in an in vitro or in vivo disease model system to identify compoundswhich affect disease progression. The subset of compounds which influencedisease in a therapeutic manner are drug leads. However, all compounds whichinfluence disease progression are tools to at least partially characterizegene function. The inhibitor identification step or the method is preferablycarried out using a plurality of microbial strains or cell lines expressingdifferent heterologous DNA sequences in a single solution. The method isparticularly useful for genes which have not been validated as good inhibitortargets.
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