Tuesday, October 15, 2024 10/15/2024

Mechanisms of Gonococcal Pilin Antigenic and Phase Variation

Award Number: R37AI033493
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract The pathogenic Neisseria are obligate human pathogens that rely on several antigenic variation systems to colonize and cause disease in the human population. This proposal will further our studies into the molecular mechanisms for pilin antigenic variation in Neisseria gonorrhoeae. High-frequency gene conversion reactions mediate extensive changes in the pilin amino acid sequence with segmental recombination between one of 18 silent pilin copies and the single expressed pilin gene. Over the tenure of this grant, we have (1) identified most of the proteins involved in this process, (2) demonstrated that the pathogenic Neisseria carry diploid chromosomes that may facilitate gene conversion, (3) shown that the formation of an alternative DNA structure called a guanine quartet (G4) is necessary for pilin antigenic variation, (4) shown that transcription of a small RNA within the G4 is necessary for pilin antigenic variation, and (5) that the small RNA forms an RNA-DNA duplex (an R-loop). We will determine how new pilin variants replace the previous ones during pilin antigenic variation. We will test the hypothesis that the G4 structure and associated R-loop initiate gene conversion by altering chromosomal DNA replication. We will define how gene conversion occurs by applying various approaches to determine the steps between the initiation of the process and the creation of the final variant pilins by defining the molecules created and the effect of specific mutants on the generation of different intermediate molecules. Finally, we will test whether the N. gonorrhoeae diploid chromosomes are involved in gene conversion. The results of these cutting-edge studies will significantly impact the analysis of (1) Neisserial pathogenesis, (2) mechanisms of antigenic variation in Neisseria and other bacterial gene conversion mechanisms, and (4) the way programmed recombination is used in many cell types to alter gene expression or content. These studies will move all these fields forward and continue pilin antigenic variation as a model for diversity generation systems that use DNA recombination.


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 = $527,985 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	31	5/22/2024	NON-COMPETING CONTINUATION	$527,985
														Subtotal = $527,985

Issue Date FY: 2023 ( Subtotal = $521,036 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	30	6/15/2023	COMPETING CONTINUATION	$521,036
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	002	30	8/15/2023	COMPETING CONTINUATION	$0
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	29	6/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $521,036

Issue Date FY: 2022 ( Subtotal = $493,498 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	29	1/27/2022	NON-COMPETING CONTINUATION	$493,498
														Subtotal = $493,498

Issue Date FY: 2021 ( Subtotal = $532,915 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	28	1/25/2021	NON-COMPETING CONTINUATION	$532,915
														Subtotal = $532,915

Issue Date FY: 2020 ( Subtotal = $492,998 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	27	8/17/2020	SUPPLEMENT FOR EXPANSION	$39,500
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	27	1/23/2020	NON-COMPETING CONTINUATION	$453,498
														Subtotal = $492,998

Issue Date FY: 2019 ( Subtotal = $453,498 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	26	1/25/2019	NON-COMPETING CONTINUATION	$453,498
														Subtotal = $453,498

Issue Date FY: 2018 ( Subtotal = $453,498 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	004	25	7/25/2018	EXTENSION WITH OR WITHOUT FUNDS	$689
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	002	25	6/6/2018	EXTENSION WITH OR WITHOUT FUNDS	$36,922
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	25	12/15/2017	EXTENSION WITH OR WITHOUT FUNDS	$453,498
2018	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	24	6/6/2018	NON-COMPETING CONTINUATION	-$36,922
2018	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	003	24	7/25/2018	NON-COMPETING CONTINUATION	-$689
														Subtotal = $453,498

Issue Date FY: 2017 ( Subtotal = $386,250 )
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	24	1/30/2017	NON-COMPETING CONTINUATION	$386,250
														Subtotal = $386,250

Issue Date FY: 2016 ( Subtotal = $386,250 )
2016	2016	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	23	1/11/2016	EXTENSION WITH OR WITHOUT FUNDS	$386,250
														Subtotal = $386,250

Issue Date FY: 2015 ( Subtotal = $386,250 )
2015	2015	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	22	1/10/2015	NON-COMPETING CONTINUATION	$386,250
														Subtotal = $386,250

Issue Date FY: 2014 ( Subtotal = $386,250 )
2014	2014	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	21	1/17/2014	NON-COMPETING CONTINUATION	$347,625
2014	2014	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	21	6/9/2014	NON-COMPETING CONTINUATION	$38,625
														Subtotal = $386,250

Issue Date FY: 2013 ( Subtotal = $363,075 )
2013	2013	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	20	2/14/2013	COMPETING CONTINUATION	$347,625
2013	2013	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	002	20	6/7/2013	COMPETING CONTINUATION	$15,450
2013	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Allergy and Infectious Diseases Research	000	19	2/13/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $363,075

Issue Date FY: 2012 ( Subtotal = $369,988 )
2012	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	19	1/26/2012	NON-COMPETING CONTINUATION	$369,988
														Subtotal = $369,988

Issue Date FY: 2011 ( Subtotal = $383,834 )
2011	2011	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	18	6/15/2011	NON-COMPETING CONTINUATION	$34,894
2011	2011	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	18	1/7/2011	NON-COMPETING CONTINUATION	$348,940
														Subtotal = $383,834

Issue Date FY: 2010 ( Subtotal = $409,964 )
2010	2010	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	17	1/14/2010	NON-COMPETING CONTINUATION	$373,725
2010	2010	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	17	8/6/2010	SUPPLEMENT FOR EXPANSION	$36,239
														Subtotal = $409,964

Issue Date FY: 2009 ( Subtotal = $504,675 )
2009	2009	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	16	12/23/2008	NON-COMPETING CONTINUATION	$339,750
2009	2009	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	002	16	9/22/2009	NON-COMPETING CONTINUATION	$127,175
2009	2009	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	16	6/16/2009	NON-COMPETING CONTINUATION	$37,750
														Subtotal = $504,675

Issue Date FY: 2008 ( Subtotal = $377,500 )
2008	2008	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Allergy and Infectious Diseases Research	000	15	1/31/2008	EXTENSION WITH OR WITHOUT FUNDS	$377,500
														Subtotal = $377,500

Issue Date FY: 2007 ( Subtotal = $316,811 )
2007	2007	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Allergy and Infectious Diseases Research	000	14	1/10/2007	NON-COMPETING CONTINUATION	$316,811
														Subtotal = $316,811

Grand Total All Awards = $9,075,581

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Mechanisms of Gonococcal Pilin Antigenic and Phase Variation

Award Number: R37AI033493

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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