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MAZEF-MEDIATED PROGRAMMED CELL DEATH NETWORK IN E. COLI

Award Number: R01GM069509
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2007
PERIOD OF PERFORMANCE END DATE: 05/31/2011

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MAZEF-MEDIATED PROGRAMMED CELL DEATH NETWORK IN E. COLI - DESCRIPTION (provided by applicant): Programmed cell death (PCD), defined as an active process which results in cell suicide, is recognized as an essential mechanism in multicellular organisms. In 1996, we reported on the first chromosomal toxin-antitoxin system discovered to be responsible for PCD in bacteria. This was the Escherichia coli (E. coli) mazEF regulateable module in which mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, that overcomes the lethal effect of MazF. Since 1996, we have made considerable progress in understanding the genetic, biochemical, structural and physiological properties of this system, and its relation to stressful conditions and the action of some well known antibiotics. In continuation of this work, here we propose to extend our research by a comprehensive characterization of a novel quorum sensing Extra-cellular Death Factor (EDF) that we were excited to discover as being a signaling peptide molecule required for E. coli mazEF-mediated cell death. Our five specific aims are as follows: 1 to characterize the exact chemical composition of E. coli EDF; 2. to elucidate the mechanism of EDF action; 3.To elucidate the relation of EDF to mazEF and to E. coli other toxin-antitoxin systems; 4.To characterize the EDF receiver(s) system; 5.To characterize EDFs of bacteria other than E. coli. The integrative research on EDF and its relation to bacterial death that we propose here should contribute to the understanding of a unique novel quorum sensing signaling molecule and its importance to bacterial PCD. Moreover, our results should also help to clarify a fundamental biological phenomenon of bacterial communication and thereby the multicellular behavior of bacterial populations. Practically, the results of our study may be useful as a basis for a novel strategy for generating a new class of antibiotics that trigger bacterial PCD, and thereby to help what has become a public health problem.


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 = $149,688 )
2010	2010	HEBREW UNIVERSITY	AUTHORITY FOR RESEARCH DEVELOPMENT	JERUSALEM				ISR	Biomedical Research and Research Training	000	4	5/12/2010	NON-COMPETING CONTINUATION	$149,688
														Subtotal = $149,688

Issue Date FY: 2009 ( Subtotal = $151,200 )
2009	2009	HEBREW UNIVERSITY	AUTHORITY FOR RESEARCH DEVELOPMENT	JERUSALEM				ISR	Biomedical Research and Research Training	000	3	5/20/2009	NON-COMPETING CONTINUATION	$151,200
														Subtotal = $151,200

Issue Date FY: 2008 ( Subtotal = $151,200 )
2008	2008	HEBREW UNIVERSITY	**	JERUSALEM		00000		ISR	Biomedical Research and Research Training	000	2	5/8/2008	NON-COMPETING CONTINUATION	$151,200
														Subtotal = $151,200

Issue Date FY: 2007 ( Subtotal = $164,160 )
2007	2007	HEBREW UNIVERSITY	**	JERUSALEM		00000		ISR	Biomedical Research and Research Training	000	1	7/13/2007	NEW	$164,160
														Subtotal = $164,160

Grand Total All Awards = $616,248

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MAZEF-MEDIATED PROGRAMMED CELL DEATH NETWORK IN E. COLI

Award Number: R01GM069509

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2007

PERIOD OF PERFORMANCE END DATE: 05/31/2011

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