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PACKAGING OF THE SEGMENTED GENOME OF BACTERIOPHAGE PHI6

Award Number: R01GM034352
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: 01/01/1985
PERIOD OF PERFORMANCE END DATE: 06/30/2009

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PACKAGING OF THE SEGMENTED GENOME OF BACTERIOPHAGE PHI6 - DESCRIPTION (provided by applicant): Bacteriophages of the family cystoviridae are unique in that they have genomes of 3 segments of double-stranded RNA packaged precisely within a preformed procapsid. Phi6 is the first member of this family and has been studied extensively. A model has been proposed for the mechanism of precise genomic packaging in phi6. The model is strongly supported by the confirmation of predicted results in both in vitro and in vivo packaging. The packaging involves the serially dependent transport of plus strands s, m and I into preformed procapsids with specificity determined by changes in the binding sites on the outside of P1, the major structural protein of the procapsid. The goal of this project is to determine the interaction of the RNA molecules with specific parts of protein P1; to identify the specific elements involved in the changing of the RNA binding sites as the packaging program procedes. This proposal is for the investigation of the location of the binding sites, their amino acid sequences and the determination of the interaction between the RNA and the binding sites. A major question posed is whether the binding sites for the different RNA molecules are physically separate from each other or whether they are overlapping and involve the same regions of protein P1. Approaches utilized in this project include the cross-linking of specific RNA molecules to their binding sites and the use of phage display libraries to locate binding sites. Collaborative structural studies are also proposed in which cores that have packaged different amounts of RNA will be examined by cryoelectron microscopy to determine their changes in conformation. This study also includes a comparative investigation of genomic packaging in the distantly related bacteriophage phi8, which seems to follow the general rules determined for phi6 but with less stringency and with a number of additional features, particularly the participation of host factors and viral genes not found in other members of the cystoviridae. The cystoviridae are the only segmented dsRNA viruses whose mode of packaging is understood. There is no current understanding of the genomic packaging of the reoviridae, segmented dsRNA viruses that cause disease in plants and animals, including humans.


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: 2008 ( Subtotal = $426,672 )
2008	2008	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Biomedical Research and Research Training	000	22	6/27/2008	NON-COMPETING CONTINUATION	$426,672
														Subtotal = $426,672

Issue Date FY: 2007 ( Subtotal = $426,754 )
2007	2007	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Biomedical Research and Research Training	000	21	6/29/2007	NON-COMPETING CONTINUATION	$426,754
														Subtotal = $426,754

Issue Date FY: 2006 ( Subtotal = $425,741 )
2006	2006	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Biomedical Research and Research Training	000	19	6/28/2006	NON-COMPETING CONTINUATION	$425,741
														Subtotal = $425,741

Issue Date FY: 2005 ( Subtotal = $423,433 )
2005	2005	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Biomedical Research and Research Training	000	18	6/24/2005	COMPETING CONTINUATION	$423,433
														Subtotal = $423,433

Issue Date FY: 2003 ( Subtotal = $370,630 )
2003	2003	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Cell Biology and Biophysics Research	000	17		NON-COMPETING CONTINUATION	$370,630
														Subtotal = $370,630

Issue Date FY: 2002 ( Subtotal = $359,834 )
2002	2002	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Cell Biology and Biophysics Research	000	16	12/24/2001	NON-COMPETING CONTINUATION	$359,834
														Subtotal = $359,834

Issue Date FY: 2001 ( Subtotal = $349,353 )
2001	2001	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	455 FIRST AVE	NEW YORK	NY	10016	NEW YORK	USA	Cell Biology and Biophysics Research	000	15	2/19/2001	NON-COMPETING CONTINUATION	$349,353
														Subtotal = $349,353

Issue Date FY: 2000 ( Subtotal = $335,008 )
2000	2000	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Cell Biology and Biophysics Research	000	14	12/20/1999	COMPETING CONTINUATION	$335,008
														Subtotal = $335,008

Issue Date FY: 1999 ( Subtotal = $93,464 )
1999	1999	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Cell Biology and Biophysics Research	001	13	3/29/1999	SUPPLEMENT FOR EXPANSION	$93,464
														Subtotal = $93,464

Issue Date FY: 1998 ( Subtotal = $292,698 )
1998	1998	PUBLIC HEALTH RESEARCH INSTITUTE OF NEW YORK CITY	225 WARREN STREET, SUITE E230F	NEWARK	NJ	07103	ESSEX	USA	Cell Biology and Biophysics Research	000	13	1/9/1998	NON-COMPETING CONTINUATION	$292,698
														Subtotal = $292,698

Grand Total All Awards = $3,503,587

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PACKAGING OF THE SEGMENTED GENOME OF BACTERIOPHAGE PHI6

Award Number: R01GM034352

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: 01/01/1985

PERIOD OF PERFORMANCE END DATE: 06/30/2009

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