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Structural Studies of Togaviruses

Award Number: R01AI095366
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: 02/20/2012
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Structural Studies of Togaviruses - PROJECT SUMMARY Crystallography was the primary structural tool that first opened up structural investigation of viruses at near-atomic resolution. For instance, the first near-atomic resolution structure of an animal virus, namely a common cold virus, was determined by us in the mid-1980s using crystallographic methods (Nature 317:145-153, 1985). However, larger viruses with lipid envelopes are too variable in their structures and have too small a proportion of their surface involved in lattice contacts to make well-ordered crystals. Cryo-electron microscopy has now emerged as the leading tool for advancing structural biology. Single particle averaging of cryo-electron microscopic images is now frequently approaching atomic resolution with the use of direct electron detection devices and technology to compensate for blurring of images due to random motion during data acquisition. However, the limits of this technology are becoming apparent in the investigations of progressively more complex pleomorphic assemblies. Cryo-electron tomography has now emerged as an invaluable tool for the determination of the structure of individual viral particles without reliance on the availability of identical homogeneous particles. However, the resolution of tomographic reconstructions is usually insufficient to determine structures in atomic detail. Thus, a small part of this grant application is dedicated towards extending the resolution of tomographic maps. Alphaviruses and rubella virus constitute the Togavirus family because of their similarity in gene order. Among alphaviruses, Chikungunya virus is a major world health concern because of its re- emergence in Asia and Africa. We plan to extend our previous studies of the icosahedral, lipid- containing alphaviruses, and tackle the more difficult structural analysis of the pleomorphic rubella virus. Specifically, we are planning to obtain the structures of various alphaviruses when complexed with host receptor molecules and with antibodies and small molecule inhibitors that block maturation, attachment and fusion with host cells in order to study the structural intermediates encountered in the viral life cycle. This information will provide viral targets that can be exploited for the design of specific antiviral therapeutics. We are also developing new technology aimed at stretching and pulling individual cryoEM images to make them more similar and homogenous to improve the resolution of tomographic images of pleomorphic biological assemblies such as rubella virus.


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: 2025 ( Subtotal = -$2,394 )
2025	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	10	5/12/2025	NON-COMPETING CONTINUATION	-$2,394
														Subtotal = -$2,394

Issue Date FY: 2023 ( Subtotal = $646,227 )
2023	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	10	1/24/2023	NON-COMPETING CONTINUATION	$646,229
2023	2021	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE STE 1900	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	8	11/3/2022	SUPPLEMENT FOR EXPANSION	-$2
														Subtotal = $646,227

Issue Date FY: 2022 ( Subtotal = $646,229 )
2022	2022	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	9	1/25/2022	NON-COMPETING CONTINUATION	$646,229
														Subtotal = $646,229

Issue Date FY: 2021 ( Subtotal = $676,399 )
2021	2021	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	8	2/18/2021	SUPPLEMENT FOR EXPANSION	$30,170
2021	2021	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	8	1/22/2021	NON-COMPETING CONTINUATION	$646,229
														Subtotal = $676,399

Issue Date FY: 2020 ( Subtotal = $1,027,692 )
2020	2020	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	7	1/29/2020	NON-COMPETING CONTINUATION	$646,229
2020	2020	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	7	4/14/2020	SUPPLEMENT FOR EXPANSION	$381,463
														Subtotal = $1,027,692

Issue Date FY: 2019 ( Subtotal = $646,229 )
2019	2019	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	002	6	8/1/2019	COMPETING CONTINUATION	$0
2019	2019	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	6	1/10/2019	COMPETING CONTINUATION	$646,229
2019	2016	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	5	5/23/2019	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $646,229

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	5	1/17/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $642,306 )
2016	2016	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	5	1/13/2016	EXTENSION WITH OR WITHOUT FUNDS	$642,306
														Subtotal = $642,306

Issue Date FY: 2015 ( Subtotal = $642,306 )
2015	2015	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	4	1/22/2015	NON-COMPETING CONTINUATION	$642,306
														Subtotal = $642,306

Issue Date FY: 2014 ( Subtotal = $642,306 )
2014	2014	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	3	1/22/2014	NON-COMPETING CONTINUATION	$578,075
2014	2014	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	002	3	7/18/2014	NON-COMPETING CONTINUATION	$0
2014	2014	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	3	6/5/2014	NON-COMPETING CONTINUATION	$64,231
														Subtotal = $642,306

Issue Date FY: 2013 ( Subtotal = $603,767 )
2013	2013	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	2	1/10/2013	NON-COMPETING CONTINUATION	$578,075
2013	2013	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	2	6/10/2013	NON-COMPETING CONTINUATION	$25,692
														Subtotal = $603,767

Issue Date FY: 2012 ( Subtotal = $642,306 )
2012	2012	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	000	1	2/17/2012	NEW	$642,306
2012	2012	PURDUE UNIVERSITY	610 PURDUE HALL	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Allergy and Infectious Diseases Research	001	1	5/2/2012	NEW	$0
														Subtotal = $642,306

Grand Total All Awards = $6,813,372

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Structural Studies of Togaviruses

Award Number: R01AI095366

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: 02/20/2012

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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