Paradigm Genetics, Inc.

Icoria, Inc.

Kiichi Adachi

Lisbeth Hamer

Jeffrey R Shuster

Todd DeZwaan

Matthew M Tanzer

Sanjoy Mahanty

Ryan Heiniger

Amy Skalchunes

Sze-Chung Lo

Huaqin Pan

Sheryl Frank

Blaise Darveaux

Maria Victoria Montenegro-Chamorro

Rex Tarpey

John E Hamer

Maria Victoria Montenegro-Chamarro

Rex Tarper

The present inventors have discovered that Asparagine Synthase is essential for fungal pathogenicity. Specifically, the inhibition of Asparagine Synthase gene expression in fungi results in no signs of successful infection or lesions. Thus, Asparagine Synthase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit Asparagine Synthase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of asparagine synthase as antibiotics

The present inventors have discovered that Threonine synthase is essential for fungal pathogenicity. Specifically, the inhibition of Threonine synthase gene expression in fungi results in no signs of successful infection or lesions. Thus, Threonine synthase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit Threonine synthase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of threonine synthase as antibiotics

The present inventors have discovered that histidinol-phosphatase is essential for fungal pathogenicity. Specifically, the inhibition of histidinol-phosphatase gene expression in fungi results in small, non-sporulating lesions and reduced pathogenicity. Thus, histidinol-phosphatase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit histidinol-phosphatase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of histidinol-phosphate as antibiotics

The present inventors have discovered that 3-Isopropylmalate dehydratase is essential for fungal pathogenicity. Specifically, the inhibition of 3-Isopropylmalate dehydratase gene expression in fungi results in no signs of successful infection or lesions. Thus, 3-Isopropylmalate dehydratase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit 3-Isopropylmalate dehydratase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of 3-isopropylmalate dehydratase as antibiotics

The present inventors have discovered that &agr;-Aminoadipate Reductase is essential for fungal pathogenicity. Specifically, the inhibition of &agr;-Aminoadipate Reductase gene expression in fungi results in no signs of successful infection or lesions. Thus, &agr;-Aminoadipate Reductase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit &agr;-Aminoadipate Reductase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of &agr;-aminoadipate reductase as antibiotics

The present inventors have discovered that 5-Aminolevulinate synthase is essential for fungal pathogenicity. Specifically, the inhibition of 5-Aminolevulinate synthase gene expression in fungi results in no signs of successful infection or lesions. Thus, 5-Aminolevulinate synthase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit 5-Aminolevulinate synthase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of 5-aminolevulinate synthase as antibiotics

The present inventors have discovered that homocitrate synthase is essential for fungal pathogenicity. Specifically, the inhibition of homocitrate synthase gene expression in fungi results in no signs of successful infection or lesions. Thus, homocitrate synthase can be used as a target for the identification of antibiotics, preferably antifungals. Accordingly, the present invention provides methods for the identification of compounds that inhibit homocitrate synthase expression or activity. The methods of the invention are useful for the identification of antibiotics, preferably antifungals.

Methods for the identification of inhibitors of homocitrate synthase as antibiotics

The present invention relates to methods for facilitating site directed homologous recombination in a eukaryotic organism to produce genomic mutants using transposon mediated mutagenesis of cosmid vectors carrying large genomic inserts from the target eukaryotic organism. The transposon carries a bifunctional marker that can be used for selection in both bacteria and the target eukaryotic organism. Minimization of the length of the cosmid vector allows for maximization of the size of the genomic insert carried by the cosmid. Maximization of the size of the genomic insert increases the frequency of homologous recombination with the genome of the target eukaryotic organism.

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Durham, NC, United States of America

Kiichi Adachi