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GIARDIA DRUG TARGETS: STRUCTURE, FUNCTION AND INHIBITORS

Award Number: R01AI059733
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2005
PERIOD OF PERFORMANCE END DATE: 09/14/2010

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GIARDIA DRUG TARGETS: STRUCTURE, FUNCTION AND INHIBITORS - DESCRIPTION (provided by applicant): Giardia lamblia is a food and waterborne parasite prevalent in developing countries, and a major cause of outbreaks of diarrhea in the United Sates, that has been classified as a bioterrorism category B organism by the Center for Disease Control because compromised water and food supply could affect US populations as well as army units in foreign countries. Drugs commonly used against anaerobic protozoa are used to treat giardiasis. However, they produce undesirable side effects, clinical resistance may occur in both immunocompromised and immunocompetent patients, and the rate of recurrence is high. The goal of this project is to develop new drug targets for alternative treatments of giardiasis. The sequence of the G. lamblia genome is available, thus, a genomic approach combined with biological insight has been taken to identify enzymes essential for the survival of the organism that are absent or are sufficiently divergent from the human enzymes to exploit those differences in the design of inhibitors. The selected enzymes will be cloned and expressed in E. coli using high throughput techniques, and those that are expressed in soluble form will be validated in G. lamblia by transcription interference methods. Essential enzymes will be prepared for structural and functional studies. Crystal structures will be determined, and will serve to guide the design of inhibitors specific to the Giardia enzymes. Assays to determine the kinetic constants of the enzymes will be developed and the catalytic mechanism will be studied to facilitate the in vitro evaluation of the inhibitors. Crystal structures of enzyme/inhibitor complexes will reveal how the inhibitor may be further improved. The effect of the inhibitors on the growth of G. lamblia will be determined. The long range goals of the project is to establish a database of potential drug targets against giardiasis, to gain insight about their mechanism of action, and to prepare inhibitors that are ready for preclinical evaluation.


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 = $0 )
2010	2009	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	5	9/3/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $568,876 )
2009	2009	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	5	6/5/2009	NON-COMPETING CONTINUATION	$56,887
2009	2009	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	5	1/12/2009	NON-COMPETING CONTINUATION	$511,989
														Subtotal = $568,876

Issue Date FY: 2008 ( Subtotal = $574,390 )
2008	2008	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	4	2/13/2008	NON-COMPETING CONTINUATION	$574,390
														Subtotal = $574,390

Issue Date FY: 2007 ( Subtotal = $569,652 )
2007	2007	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	3	1/26/2007	NON-COMPETING CONTINUATION	$569,652
														Subtotal = $569,652

Issue Date FY: 2006 ( Subtotal = $570,802 )
2006	2006	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	2	1/26/2006	NON-COMPETING CONTINUATION	$570,802
														Subtotal = $570,802

Issue Date FY: 2005 ( Subtotal = $603,128 )
2005	2005	MARYLAND BIOTECHNOLOGY INSTITUTE	701 E PRATT STREET, SUITE 200	BALTIMORE	MD	21202	BALTIMORE CITY	USA	Microbiology and Infectious Diseases Research	000	1	1/20/2005	NEW	$603,128
														Subtotal = $603,128

Grand Total All Awards = $2,886,848

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GIARDIA DRUG TARGETS: STRUCTURE, FUNCTION AND INHIBITORS

Award Number: R01AI059733

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2005

PERIOD OF PERFORMANCE END DATE: 09/14/2010

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