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Ixodes scapularis Immuno-Developmental and Metabolic Signaling Pathways and Interference with Ticks and Tick-borne Pathogens

Award Number: P01AI138949
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: 07/13/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2030

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Ixodes scapularis Immuno-Developmental and Metabolic Signaling Pathways and Interference with Ticks and Tick-borne Pathogens - OVERALL – Abstract The proposed renewal Program Project (P01), entitled “Ixodes scapularis Immuno-Developmental and Metabolic Signaling Pathways and Interference with Ticks and Tick-borne Pathogens”, aims to understand the molecular mechanisms by which a set of newly recognized I. scapularis conserved signaling pathways, either discretely or via synergism, govern key episodes of arthropod development, metabolism, and immunobiology that shape their vectorial competence for the harboring and transmission of agents of Lyme disease and anaplasmosis. We have discovered unorthodox aspects of tick signaling pathways that involve mammalian-arthropodal crosstalk and are triggered by ingested cytokines, scavenger receptor-like proteins, or hormones, and influence tick microbicidal responses, development, and/or metabolism, as exemplified by the Dome1-JAK-STAT, immune deficiency (IMD), and adiponectin receptor-like protein (ISARL) signaling pathways. We have also established that suppressing the expression of select key extracellular components of these signaling pathways, such as via RNA interference-mediated knockdown of cell surface tick receptors or extracellular molecules, interrupts tick engorgement or pathogen transmission. In this renewal application, which builds on these paradigms and combines the complementary expertise and resources from four institutions with impressive histories of research involving tick-borne infections, we propose to further characterize these signaling pathways and explore whether essential cell surface tick receptors, domains, and/or extracellular molecules could be targeted as novel anti-tick vaccines to impede essential aspects of vector biology and tick-pathogen life cycles. Two of the most widespread and emerging bacterial pathogens, Borrelia burgdorferi and Anaplasma phagocytophilum, remain our focus as prototypic examples of tick- transmitted extracellular and intracellular microbes, respectively. This renewal Program Project Grant leverages specific assays, tools, and methodologies developed by our laboratories, supported by an Administrative Core and Tick Resources Core, whereby new information as well as organisms, cell lines, and resources will be generated and shared, not only among the P01 team, but also with broader scientific communities via open-source databases, platforms, and the project website. The proposed goals are to: 1) Operate Resource Cores that provide research reagents and information to all Projects and the scientific community; 2) Characterize signaling pathways regulating vector immune-developmental cascades; 3) Investigate metabolic pathways regulating tick immune responses; and 4) Explore tick immune-developmental and metabolic pathways as anti-tick vaccine targets. Altogether, this proposal will increase our understanding of atypical tick biology and advance the development of new preventions against major tick-borne infections, while also planting new seeds of innovative research in vector-borne infections and enticing a new generation of scientists to engage in and advance this important yet neglected field of scientific research.


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: 2026 ( Subtotal = $1,898,910 )
2026	2026	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	7	2/2/2026	NON-COMPETING CONTINUATION	$1,898,910
														Subtotal = $1,898,910

Issue Date FY: 2025 ( Subtotal = $1,941,828 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	6	1/30/2025	COMPETING CONTINUATION	$1,941,828
2025	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	5	2/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,941,828

Issue Date FY: 2022 ( Subtotal = $1,537,478 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	7/28/2022	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2021 ( Subtotal = $1,537,478 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	4	6/29/2021	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2020 ( Subtotal = $1,537,478 )
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	3	7/23/2020	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2019 ( Subtotal = $1,537,478 )
2019	2019	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	2	7/10/2019	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2018 ( Subtotal = $1,578,353 )
2018	2018	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	1	7/12/2018	NEW	$1,578,353
														Subtotal = $1,578,353

Grand Total All Awards = $11,569,003

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Ixodes scapularis Immuno-Developmental and Metabolic Signaling Pathways and Interference with Ticks and Tick-borne Pathogens

Award Number: P01AI138949

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: 07/13/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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