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Control of Virus Induced Lysis

Award Number: R01GM027099
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: 01/01/1980
PERIOD OF PERFORMANCE END DATE: 06/30/2020

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Control of Virus Induced Lysis - Project Summary The focus is on the mechanism by which bacterial viruses (phages) achieve destruction (lysis) of the host cell and release of the viral progeny. The Gram-negative bacterial cell has three layers: the cytoplasmic or inner membrane (IM), the cell wall or peptidoglycan (PG), and the outer membrane (OM). Recent progress has revealed that dsDNA phages that dominate the biosphere encode three types of proteins, each responsible for attacking one of the three components of the cell wall. The overall process is controlled by holins, small proteins that accumulate in the IM for typically 15 to 60 minutes, when, suddenly, they trigger to form holes. The sudden formation of these membrane holes kills the cell and instantly stops all energy metabolism, marking the end of the infection cycle. This allows another class of proteins called endolysins are able to attack the cell wall, degrading the sugar-sugar or peptide linkages. Once the PG network is destroyed, a newly discovered class of proteins, called the spanins, conducts the final step. Spanins connect the IM to the OM through the PG meshwork. Once that meshwork is destroyed, the spanins undergo a conformational change and disrupt the OM. We will test a model that the destruction of the OM is the result of membrane fusion with the IM, thus removing the last barrier to virus release. The first Aim is to characterize the spanins at the molecular and structural levels, using genetics, molecular biology, cell biology, ultrastructural microscopy, biochemistry and structural studies. The second Aim, a major collaborative effort with the co-PI Dr. J. Xiao of Johns Hopkins, is focused on using super-resolution microscopy in achieving a complete description of the lysis process in four dimensions (space and place in the cell, as well as time in the infection cycle.) These studies will further our understanding of how bacterial viruses, or phages, kill their prey and effect dispersal of their progeny. Besides illuminating many fundamental processes, this may have direct practical benefits because there is a growing consensus that phages, as natural antibacterial agents, will become an important tool in combating bacterial pathogens, which are increasingly resistant to available antibiotics.


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: 2022 ( Subtotal = -$149 )
2022	2019	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	002	38	6/29/2022	NON-COMPETING CONTINUATION	-$149
2022	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	37	6/29/2022	NON-COMPETING CONTINUATION	$0
2022	2017	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	36	6/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = -$149

Issue Date FY: 2021 ( Subtotal = -$483 )
2021	2019	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	38	12/28/2020	NON-COMPETING CONTINUATION	-$483
														Subtotal = -$483

Issue Date FY: 2019 ( Subtotal = $329,386 )
2019	2019	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	38	8/1/2019	NON-COMPETING CONTINUATION	$329,386
														Subtotal = $329,386

Issue Date FY: 2018 ( Subtotal = $329,879 )
2018	2018	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	37	7/17/2018	NON-COMPETING CONTINUATION	$329,879
														Subtotal = $329,879

Issue Date FY: 2017 ( Subtotal = $330,347 )
2017	2017	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	36	6/20/2017	NON-COMPETING CONTINUATION	$330,347
2017	2014	TEXAS A & M RESEARCH FOUNDATION	400 HARVEY MITCHELL PKWY STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	34	1/21/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $330,347

Issue Date FY: 2016 ( Subtotal = $439,156 )
2016	2016	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	003	35	9/1/2016	SUPPLEMENT FOR EXPANSION	$97,426
2016	2016	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	002	35	8/22/2016	COMPETING CONTINUATION	$341,730
2016	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	34	8/17/2016	NON-COMPETING CONTINUATION	$0
2016	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	34	3/1/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $439,156

Issue Date FY: 2014 ( Subtotal = $277,644 )
2014	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	34	4/17/2014	NON-COMPETING CONTINUATION	$277,644
														Subtotal = $277,644

Issue Date FY: 2013 ( Subtotal = $267,926 )
2013	2013	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	33	3/22/2013	NON-COMPETING CONTINUATION	$249,880
2013	2013	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	33	6/19/2013	NON-COMPETING CONTINUATION	$18,046
														Subtotal = $267,926

Issue Date FY: 2012 ( Subtotal = $277,644 )
2012	2012	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	32	4/11/2012	NON-COMPETING CONTINUATION	$277,644
														Subtotal = $277,644

Issue Date FY: 2011 ( Subtotal = $277,644 )
2011	2011	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	31	4/15/2011	COMPETING CONTINUATION	$277,644
														Subtotal = $277,644

Issue Date FY: 2009 ( Subtotal = $620,299 )
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	30	12/19/2008	NON-COMPETING CONTINUATION	$433,068
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Trans-NIH Recovery Act Research Support	002	30	9/22/2009	SUPPLEMENT FOR EXPANSION	$139,113
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	30	3/31/2009	NON-COMPETING CONTINUATION	$48,118
														Subtotal = $620,299

Issue Date FY: 2008 ( Subtotal = $472,212 )
2008	2008	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	29	2/25/2008	NON-COMPETING CONTINUATION	$472,212
														Subtotal = $472,212

Issue Date FY: 2007 ( Subtotal = $477,350 )
2007	2007	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	28	12/22/2006	NON-COMPETING CONTINUATION	$477,350
														Subtotal = $477,350

Issue Date FY: 2006 ( Subtotal = $482,639 )
2006	2006	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	27	12/27/2005	COMPETING CONTINUATION	$482,639
														Subtotal = $482,639

Grand Total All Awards = $4,581,494

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Control of Virus Induced Lysis

Award Number: R01GM027099

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: 01/01/1980

PERIOD OF PERFORMANCE END DATE: 06/30/2020

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