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IN VIVO PROFILING FOR ORAL CANDIDIASIS DRUG TARGET DISCOVERY

Award Number: R44DE017033
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2005
PERIOD OF PERFORMANCE END DATE: 03/31/2011

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IN VIVO PROFILING FOR ORAL CANDIDIASIS DRUG TARGET DISCOVERY - DESCRIPTION (provided by applicant): Candida albicans is the most frequently isolated fungal pathogen of humans and represents an important public health problem. However, antifungal treatments are hampered by emerging resistance, toxicity concerns, lack of fungicidal activity, and narrow spectrum of action. Thus, there is a critical need for new antifungal drug targets, and new antifungal drug strategies. An important step in the identification of new targets for antifungal drug discovery is the use of in vivo genome profiling using appropriate diseased samples to identify fungal-specific genes which are required for infection. The Phase I application successfully utilized emerging technologies to identify C. albicans genes induced during murine oral candidiasis. Specifically, we identified a subset of: (i) in vivo expressed genes; (ii) infection and colonization-associated genes, and (iii) novel and fungal-specific genes that will likely play a role in the transition from comced targets identified during the Phase I research are required for oral infection. Specific C. albicans knockout strains will be generated and assessed for their ability to cause disease during oral candidiasis. Specific Aim 2 will demonstrate that oligonucleotides can function as antifungal agents against Candida species in vitro. Oligonucleotides will be designed against pre-existing antifungal drug targets and against infection- required targets identified in Specific Aim 1. The oligonucleotides will be preferentially designed against domains within the gene open reading frame that are conserved amongst pathogenic fungi. The antifungal capability of the oligonucleotides will be assessed specifically at the mRNA level, and analyzed for the corresponding alterations in growth, viability, or specific phenotype trait. Specific Aim 3 will demonstrate that the oligonucleotides can be used alone, and in combination with known antifungal agents, to treat murine oral candidiasis. The rese Mucosal candidiasis is the mostcommon type of Candida infection and occurs frequently in immunocompromised patients, and patients with an altered bacterial flora. Despite the large number of at risk patients, antifungal treatment is hampered by toxic side effects and emerging antifungal resistant Candida strains and species.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2010 ( Subtotal = $330,143 )
2010	2010	GUILD ASSOCIATES INC	5750 SHIER RINGS	DUBLIN	OH	43016	FRANKLIN	USA	Oral Diseases and Disorders Research	000	3	7/23/2010	NON-COMPETING CONTINUATION	$330,143
														Subtotal = $330,143

Issue Date FY: 2009 ( Subtotal = $394,339 )
2009	2009	GUILD ASSOCIATES INC	5750 SHIER RINGS	DUBLIN	OH	43016	FRANKLIN	USA	Oral Diseases and Disorders Research	000	2	7/29/2009	COMPETING CONTINUATION	$394,339
														Subtotal = $394,339

Grand Total All Awards = $724,482

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IN VIVO PROFILING FOR ORAL CANDIDIASIS DRUG TARGET DISCOVERY

Award Number: R44DE017033

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2005

PERIOD OF PERFORMANCE END DATE: 03/31/2011

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