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M. TUBERCULOSIS & HOST GENE EXPRESSION DURING INFECTION

Award Number: R01HL068513
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2001
PERIOD OF PERFORMANCE END DATE: 07/31/2006

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M. TUBERCULOSIS & HOST GENE EXPRESSION DURING INFECTION - DESCRIPTION (provided by applicant) The sequencing of many genomes has led to the development of new technologies for studying gene expression in prokaryotic and eukaryotic cells. These techniques, especially gene expression profiling with DNA arrays are revolutionizing studies of microbial physiology, eg, cellular responses to different growth conditions and environmental stimuli, etc. These new methods can also be used to study bacterial and/or host gene expression during infections, as they facilitate transcriptional analyses of the interaction between bacterial pathogens and their host. The purpose of this grant application is to do an integrated study of bacterial and host gene expression during M. tuberculosis infection of macrophages and animals, using standard DNA array technology and by developing new methods, as well. The aims of the project are as follows: 1) Expression profiling of M. tuberculosis genes in vitro and during infection.We will use DNA arrays containing the entire M. tuberculosis4000 gene set (Mtb gene array) to study the levels of all the mRNAs of wild type and mutant M. tuberculosis. in vitro in response to various environmental stresses. The arrays will also be used to study the levels of mRNAs of wild type and mutant M. tuberculosis during infection of human and mouse macrophage cell lines. We will also develop molecular beacon derived methods described in specific aim 3 to study the expression of M. tuberculosis genes in different tissues during the infection of animals. 2) the second major aim is to do expression profiling of host genes during M. tuberculosis infections. For these studies, we will use Affymetrix or custom arrays of the human and mouse genomes to study host gene expression during M. tuberculosis infection of macrophages and during later stages of infecrtion in different tissues of infected animals. 3) the final aim is to develop new methods for studying M. tuberculosis gene expression during animal infections. These methods will use molecular beacons and related techniques for fixed arrays that will allow the detection and quantitation of multiple M. tuberculosis mRNAs during infection and will employ specific amplification during hybridization so that low levels of bacterial mRNAs can be specifically detected in the presence of high levels of host RNA.


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: 2005 ( Subtotal = $538,376 )
2005	2005	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Lung Diseases Research	000	5	8/17/2005	NON-COMPETING CONTINUATION	$538,376
														Subtotal = $538,376

Issue Date FY: 2004 ( Subtotal = $538,376 )
2004	2004	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Lung Diseases Research	000	4	7/30/2004	NON-COMPETING CONTINUATION	$538,376
														Subtotal = $538,376

Issue Date FY: 2003 ( Subtotal = $574,164 )
2003	2003	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Lung Diseases Research	001	2	6/16/2003	SUPPLEMENT FOR EXPANSION	$35,788
2003	2003	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Lung Diseases Research	000	3	8/4/2003	NON-COMPETING CONTINUATION	$538,376
														Subtotal = $574,164

Issue Date FY: 2002 ( Subtotal = $466,800 )
2002	2002	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Lung Diseases Research	000	2	9/23/2002	NON-COMPETING CONTINUATION	$466,800
														Subtotal = $466,800

Issue Date FY: 2001 ( Subtotal = $466,800 )
2001	2001	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	455 FIRST AVE	NEW YORK	NY	10016	NEW YORK	USA	Lung Diseases Research	000	1	9/7/2001	NEW	$466,800
														Subtotal = $466,800

Grand Total All Awards = $2,584,516

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M. TUBERCULOSIS & HOST GENE EXPRESSION DURING INFECTION

Award Number: R01HL068513

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2001

PERIOD OF PERFORMANCE END DATE: 07/31/2006

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