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Function and regulation of two key serine proteases in insect immunity

Award Number: R01GM058634
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: 03/01/1999
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Function and regulation of two key serine proteases in insect immunity - Project Summary Extracellular serine proteases and their non-catalytic homologs coordinate key defense mechanisms in insects. This includes responses of mosquitoes against pathogens and parasites that cause serious human diseases. Proteolytic cleavage generates active phenoloxidases (POs), thioester proteins (TEPs), Spätzle and other cytokines. PO catalyzes the production of reactive chemicals to sequester and kill the invading organisms. TEPs opsonize parasites, targeting them for destruction. Spätzle and other cytokines trigger intracellular signaling pathways to induce the expression of antimicrobial peptides and other defense proteins. In insect vectors of human diseases, the protease networks may be evaded or disrupted by proteins from the intruders. Knowledge of the system components and their interactions from biochemical model insects such as Manduca sexta is useful for gaining detailed molecular understanding of fundamental aspects of insect innate immunity, including these protease cascades and provides basic knowledge that can guide studies of similar systems in insect disease vectors. We have elucidated a part of the M. sexta protease network that activates proPO in response to bacteria and fungi. In this network, recognition proteins bind to microbes and activate the proteases in a cascade mode. We have annotated 193 genes encoding serine proteases and their homologs, identified 36 of the proteins in larval hemolymph, and acquired data indicating that some of them play critical roles in immune signal transduction. Based on the molecular probes, purified proteins and working experience, we propose to investigate two critical steps of the protease network, which are conserved in dipteran species, by combining hemolymph fractionation, recombinant protein production and processing, sequence and expression information, and state-of-the-art mass spectrometry. The specific aims of this project are to: 1) characterize the system initiation by examining interactions of peptidoglycans, two recognition proteins, and hemolymph protease-14 precursor (proHP14) at the domain level; 2) identify 1−2 proHP6-activating proteases and elucidate their activation mechanisms. New knowledge gained in this project will improve understanding of insect immunity at a biochemical level and stimulate related research in vector species.


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 = $0 )
2025	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	18	12/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	18	6/16/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $345,504 )
2022	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	18	8/22/2022	NON-COMPETING CONTINUATION	$345,504
														Subtotal = $345,504

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	17	9/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $349,787 )
2020	2020	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	17	8/24/2020	NON-COMPETING CONTINUATION	$349,787
														Subtotal = $349,787

Issue Date FY: 2019 ( Subtotal = $353,983 )
2019	2019	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	16	8/16/2019	NON-COMPETING CONTINUATION	$353,983
														Subtotal = $353,983

Issue Date FY: 2018 ( Subtotal = $466,993 )
2018	2018	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	15	9/18/2018	COMPETING CONTINUATION	$466,993
														Subtotal = $466,993

Issue Date FY: 2014 ( Subtotal = $0 )
2014	2012	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	14	9/4/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $221,050 )
2012	2012	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	14	8/29/2012	NON-COMPETING CONTINUATION	$221,050
														Subtotal = $221,050

Issue Date FY: 2011 ( Subtotal = $221,050 )
2011	2011	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	13	8/19/2011	NON-COMPETING CONTINUATION	$221,050
														Subtotal = $221,050

Issue Date FY: 2010 ( Subtotal = $223,283 )
2010	2010	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	12	8/27/2010	NON-COMPETING CONTINUATION	$223,283
														Subtotal = $223,283

Issue Date FY: 2009 ( Subtotal = $263,713 )
2009	2009	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	001	11	9/15/2009	COMPETING CONTINUATION	$263,713
2009	2008	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	10	9/15/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $263,713

Issue Date FY: 2008 ( Subtotal = $215,901 )
2008	2008	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	10	3/10/2008	NON-COMPETING CONTINUATION	$215,901
														Subtotal = $215,901

Issue Date FY: 2007 ( Subtotal = $215,901 )
2007	2007	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	9	3/7/2007	NON-COMPETING CONTINUATION	$215,901
														Subtotal = $215,901

Issue Date FY: 2006 ( Subtotal = $222,349 )
2006	2006	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	8	2/27/2006	NON-COMPETING CONTINUATION	$222,349
														Subtotal = $222,349

Issue Date FY: 2005 ( Subtotal = $263,815 )
2005	2005	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Biomedical Research and Research Training	000	7	2/28/2005	COMPETING CONTINUATION	$263,815
														Subtotal = $263,815

Issue Date FY: 2003 ( Subtotal = $157,272 )
2003	2003	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Cell Biology and Biophysics Research	000	6		NON-COMPETING CONTINUATION	$157,272
														Subtotal = $157,272

Issue Date FY: 2002 ( Subtotal = $152,990 )
2002	2002	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Cell Biology and Biophysics Research	000	5	3/4/2002	NON-COMPETING CONTINUATION	$152,990
														Subtotal = $152,990

Issue Date FY: 2001 ( Subtotal = $148,429 )
2001	2001	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Cell Biology and Biophysics Research	000	4	2/23/2001	NON-COMPETING CONTINUATION	$148,429
														Subtotal = $148,429

Issue Date FY: 2000 ( Subtotal = $140,512 )
2000	2000	KANSAS STATE UNIVERSITY, AGRICULTURE & APPLIED SCIENCE	ANDERSON HALL ROOM 206	MANHATTAN	KS	66506	RILEY	USA	Cell Biology and Biophysics Research	000	2	8/4/2000	NON-COMPETING CONTINUATION	$1
2000	2000	OKLAHOMA STATE UNIVERSITY, GRANTS & CONTRACTS FIN ADM	203 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Cell Biology and Biophysics Research	000	3	8/7/2000	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$140,511
														Subtotal = $140,512

Issue Date FY: 1999 ( Subtotal = $187,018 )
1999	1999	KANSAS STATE UNIVERSITY, AGRICULTURE & APPLIED SCIENCE	ANDERSON HALL ROOM 206	MANHATTAN	KS	66506	RILEY	USA	Cell Biology and Biophysics Research	000	1	3/1/1999	NEW	$187,018
														Subtotal = $187,018

Grand Total All Awards = $4,149,550

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Function and regulation of two key serine proteases in insect immunity

Award Number: R01GM058634

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: 03/01/1999

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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