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Assembly of Picornaviral Replication Complexes

Award Number: R01AI059130
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Assembly of Picornaviral Replication Complexes - The picornaviruses are a family of small positive sense single stranded RNA viruses that cause a wide range of diseases at an annual cost well into the hundreds of million dollars. Members include acute hepatitis A virus, the heart disease causing coxsackie B3 virus, rhinoviruses that cause more than half the occurrences of the common cold, and the paralyzing poliovirus. These viruses share a life cycle where RNA replication and viral assembly occurs in large membrane anchored replication complexes assembled on the surfaces of vesicles derived from the endoplasmic reticulum. The replication process is driven by a virally encoded RNA dependent RNA polymerase (3Dpol) that is responsible for the synthesis of all viral RNA. This research project is focused on the structure and assembly of the viral replication centers and on structure-function studies of the viral polymerases to understand mechanisms that control of elongation rates and replication fidelity. We have solved multiple crystal structures of 3Dpol as elongation complexes with bound RNA and these structures revealed a novel mechanism by which RdRPs close their active sites for catalysis in response to nucleotide binding. In this upcoming project period we will use biophysical and structural biology methods to further our mechanistic understanding of RNA translocation by 3Dpol and to solve the structures of viral initiation and uridylylation complexes. We will also use single molecule microscopy and particle tracking methods to directly visualize the in vitro assembly of viral replication complexes onto supported lipid bilayers.


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: 2024 ( Subtotal = -$74,375 )
2024	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	15	2/22/2024	NON-COMPETING CONTINUATION	-$74,375
														Subtotal = -$74,375

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	001	15	2/23/2023	NON-COMPETING CONTINUATION	$0
2023	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	15	2/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $377,640 )
2021	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	15	1/15/2021	NON-COMPETING CONTINUATION	$377,640
														Subtotal = $377,640

Issue Date FY: 2020 ( Subtotal = $377,640 )
2020	2020	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	14	1/24/2020	NON-COMPETING CONTINUATION	$377,640
														Subtotal = $377,640

Issue Date FY: 2019 ( Subtotal = $377,640 )
2019	2019	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	13	1/14/2019	NON-COMPETING CONTINUATION	$377,640
														Subtotal = $377,640

Issue Date FY: 2018 ( Subtotal = $377,640 )
2018	2018	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	12	1/22/2018	NON-COMPETING CONTINUATION	$377,640
														Subtotal = $377,640

Issue Date FY: 2017 ( Subtotal = $376,618 )
2017	2017	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	003	11	8/30/2017	COMPETING CONTINUATION	$24,760
2017	2017	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	002	11	7/5/2017	COMPETING CONTINUATION	$0
2017	2017	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	001	11	2/10/2017	COMPETING CONTINUATION	$351,858
2017	2014	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	10	11/3/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $376,618

Issue Date FY: 2014 ( Subtotal = $291,060 )
2014	2014	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	10	5/12/2014	NON-COMPETING CONTINUATION	$291,060
														Subtotal = $291,060

Issue Date FY: 2013 ( Subtotal = $273,596 )
2013	2013	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	9	5/6/2013	NON-COMPETING CONTINUATION	$273,596
														Subtotal = $273,596

Issue Date FY: 2012 ( Subtotal = $341,060 )
2012	2012	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	8	5/9/2012	NON-COMPETING CONTINUATION	$291,060
2012	2012	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	001	8	9/13/2012	NON-COMPETING CONTINUATION	$50,000
														Subtotal = $341,060

Issue Date FY: 2011 ( Subtotal = $291,060 )
2011	2011	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	7	6/7/2011	NON-COMPETING CONTINUATION	$291,060
														Subtotal = $291,060

Issue Date FY: 2010 ( Subtotal = $294,000 )
2010	2010	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	6	6/11/2010	COMPETING CONTINUATION	$294,000
														Subtotal = $294,000

Issue Date FY: 2009 ( Subtotal = $0 )
2009	2008	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	5	9/28/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $233,790 )
2008	2008	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	5	3/6/2008	NON-COMPETING CONTINUATION	$233,790
														Subtotal = $233,790

Issue Date FY: 2007 ( Subtotal = $238,318 )
2007	2007	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 408	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	4	3/15/2007	NON-COMPETING CONTINUATION	$238,318
														Subtotal = $238,318

Issue Date FY: 2006 ( Subtotal = $245,436 )
2006	2006	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 211	FORT COLLINS	CO	80523	LARIMER	USA	Allergy and Infectious Diseases Research	000	3	3/6/2006	NON-COMPETING CONTINUATION	$245,436
														Subtotal = $245,436

Issue Date FY: 2005 ( Subtotal = $251,342 )
2005	2005	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 211	FORT COLLINS	CO	80523	LARIMER	USA	Microbiology and Infectious Diseases Research	000	2	3/28/2005	NON-COMPETING CONTINUATION	$251,342
														Subtotal = $251,342

Issue Date FY: 2004 ( Subtotal = $251,342 )
2004	2004	COLORADO STATE UNIVERSITY	UNIV SERVICES CENTER, ROOM 211	FORT COLLINS	CO	80523	LARIMER	USA	Microbiology and Infectious Diseases Research	000	1	3/4/2004	NEW	$251,342
														Subtotal = $251,342

Grand Total All Awards = $4,523,807

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Assembly of Picornaviral Replication Complexes

Award Number: R01AI059130

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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