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An Integrated In Vitro 3D Model of Human Bone Marrow and Peripheral Infection

Award Number: R01EB030410
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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An Integrated In Vitro 3D Model of Human Bone Marrow and Peripheral Infection - PROJECT SUMMARY The immune response to a peripheral infection is a fundamental feature of the human immune system, providing robust protection from a myriad of infectious agents. The response necessarily invokes the innate immune system, but many features of this orchestrated response are poorly understood, limiting our ability to augment the response to new and ever evolving threats. In particular, the innate response engages the bone marrow to modify the magnitude and dynamics of the response. There are important differences between the mouse (primary model to study the innate immune response) and human innate immune responses, in particular scale and dynamics, and new technologies in 3D cell and tissue culture provide exciting opportunities in the field known as “organ-on-a-chip”. The primary goal of this project is to design, build, and validate an integrated human “ImmuneChip” platform that mimics key dynamic features of the production and trafficking of polymorphonuclear leukocytes (PMN, i.e., neutrophils) between the bone marrow, systemic circulation, and peripheral site of bacterial infection. Developing this technology is important because of the alarming expansion of antibiotic resistance bacteria which will demand creative and alternative approaches to combat. The specific aims are to: 1) design, build, and test a microfluidic ImmuneChip that simulates the homeostatic interaction between bone marrow, systemic circulation, and a sterile skin model; 2) establish a homeostatic circuit in the ImmuneChip in which HSPC expansion, PMN trafficking, and antimicrobial defenses respond to soluble mediators of bacterial infection; and 3) demonstrate an appropriate response to contain a methicillin-resistant (and sensitive) S. aureus peripheral infection within the ImmuneChip, and produce a test- bed for novel biological strategies to combat infection. The in vitro model will be able to uniquely simulate the dynamics of peripheral infection-bone marrow communication including transport barriers, residence time in the circulation, and dilution due to the large difference in the size of the compartments. Accomplishing our primary goal will create a technology that advances a new class of model systems to understand the human response to peripheral infection.


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	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	10/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $585,004 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	6/12/2024	NON-COMPETING CONTINUATION	$585,004
														Subtotal = $585,004

Issue Date FY: 2023 ( Subtotal = $678,182 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	6/1/2023	SUPPLEMENT FOR EXPANSION	$62,962
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	5/31/2023	NON-COMPETING CONTINUATION	$615,220
														Subtotal = $678,182

Issue Date FY: 2022 ( Subtotal = $716,067 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	6/16/2022	NON-COMPETING CONTINUATION	$628,362
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	4/8/2022	SUPPLEMENT FOR EXPANSION	$12,404
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	2	9/16/2022	SUPPLEMENT FOR EXPANSION	$75,301
														Subtotal = $716,067

Issue Date FY: 2021 ( Subtotal = $641,127 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/13/2021	NEW	$641,127
														Subtotal = $641,127

Grand Total All Awards = $2,620,380

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An Integrated In Vitro 3D Model of Human Bone Marrow and Peripheral Infection

Award Number: R01EB030410

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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