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ORGANIZATION AND FUNCTION OF A TYPE II SECRETION COMPLEX

Award Number: R01AI049294
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: 04/01/2001
PERIOD OF PERFORMANCE END DATE: 06/30/2013

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ORGANIZATION AND FUNCTION OF A TYPE II SECRETION COMPLEX - Extracellular secretion and targeted delivery by the type II secretion (T2S) system is considered a major virulence mechanism in gram negative pathogens, as many of the proteins secreted via the T2S pathway constitute important virulence factors, including toxins and degradative enzymes. The T2S apparatus is comprised of at least 13 different proteins, EpsC-EpsN and PilD, that assemble into a complex that spans the entire cell envelope of Vibrio cholerae. The dynamic and perhaps transient nature of this complex may be a prerequisite for function as its assembly and disassembly may drive extracellular secretion. The energy required for this process is thought to be generated from ATP hydrolysis by EpsE, a cytoplasmic protein that is associated with the cytoplasmic membrane via interaction with the membrane proteins EpsL. EpsM and EpsF. EpsE's interactions with these components modulate its ATPase activity and promote its localization to distinct sites within the V. cholerae cell envelope. The experiments described in this proposal are designed to test the hypothesis that specific protein-protein interactions and acidic phospholipids drive T2S in an ATP-dependent process at discrete sites In the cell envelope of V. cho/erae. Specffically, this proposal will i) determine the mechanism by which the enzymatic activity of EpsE is controlled by components of the cytoplasmic membrane including phospholipids. EpsL and EpsF; ii) investigate the ordered assembly of Eps components and determine the mechanism by which EpsD and EpsC drive focal assembly of the T2S complex; iii) map the cleft that forms when EpsM assembles and identify the cellular factor that binds to the cleft. Resolving the mechanisms of regulated assembly and spatial localization of the T2S system will further our understanding of T2S and may identify ways to manipulate the secretion process for preventative, therapeutic and/or biotechnological use.


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: 2012 ( Subtotal = $378,352 )
2012	2012	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	11	6/13/2012	NON-COMPETING CONTINUATION	$378,352
														Subtotal = $378,352

Issue Date FY: 2011 ( Subtotal = $378,536 )
2011	2011	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	001	10	7/1/2011	EXTENSION WITH OR WITHOUT FUNDS	$378,536
2011	2010	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Trans-NIH Recovery Act Research Support	000	9	6/30/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $378,536

Issue Date FY: 2010 ( Subtotal = $380,179 )
2010	2010	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Trans-NIH Recovery Act Research Support	000	9	5/19/2010	NON-COMPETING CONTINUATION	$380,179
														Subtotal = $380,179

Issue Date FY: 2009 ( Subtotal = $380,179 )
2009	2009	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Trans-NIH Recovery Act Research Support	001	8	5/28/2009	COMPETING CONTINUATION	$380,179
2009	2006	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	7	5/28/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $380,179

Issue Date FY: 2006 ( Subtotal = $351,240 )
2006	2006	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Allergy and Infectious Diseases Research	000	7	6/19/2006	NON-COMPETING CONTINUATION	$351,240
														Subtotal = $351,240

Issue Date FY: 2005 ( Subtotal = $346,915 )
2005	2005	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Microbiology and Infectious Diseases Research	000	5	3/30/2005	NON-COMPETING CONTINUATION	$346,915
														Subtotal = $346,915

Issue Date FY: 2004 ( Subtotal = $231,300 )
2004	2004	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Microbiology and Infectious Diseases Research	000	4	8/27/2004	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$231,299
2004	2004	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Microbiology and Infectious Diseases Research	000	3	2/5/2004	NON-COMPETING CONTINUATION	$1
														Subtotal = $231,300

Issue Date FY: 2003 ( Subtotal = $231,300 )
2003	2003	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Microbiology and Infectious Diseases Research	000	2		NON-COMPETING CONTINUATION	$231,300
														Subtotal = $231,300

Issue Date FY: 2002 ( Subtotal = $231,300 )
2002	2002	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Microbiology and Infectious Diseases Research	000	1	1/31/2002	NEW	$231,300
														Subtotal = $231,300

Grand Total All Awards = $2,909,301

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ORGANIZATION AND FUNCTION OF A TYPE II SECRETION COMPLEX

Award Number: R01AI049294

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: 04/01/2001

PERIOD OF PERFORMANCE END DATE: 06/30/2013

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