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Photoresponsive materials to study matricellular signaling dynamics during crypt formation and fission

Award Number: R01DK120921
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Photoresponsive materials to study matricellular signaling dynamics during crypt formation and fission - ABSTRACT The small intestine is lined with a single layer of epithelial cells that is organized into crypt-villus units. These epithelial cells perform multiple functions, such as aiding in digestion, nutrient absorbance, and serving as a barrier, but these processes also damage the epithelial layer. As a result, intestinal stem cell (ISCs) located near the base of crypts are responsible for the constant renewal and rapid replenishment of all intestinal cell types, but the crypts themselves also require maintenance through a process called fission. Crypt fission occurs when a single intestinal crypt divides and generates a new daughter crypt, which is essential for maintaining overall crypt density and intestinal health. Despite the important role of crypt fission in injury-induced crypt regeneration and its mis-regulation in intestinal diseases (e.g., inflammatory bowel disease), little is known about the mechanisms of how crypt fission is initiated, progresses through crypt bifurcation, and is regulated under different pathophysiological conditions. Thus, the proposed research aims to use photoresponsive hydrogels for the culture of intestinal organoids and then develop a robust and predictable in vitro model of crypt fission events. Our innovative materials and reductionist approach will allow us to precisely tune the properties of the ISC niche and understand how epithelial cells and ECM signaling contribute to crypt formation and fission. We will test hypotheses related to the role of crypt cells and matricellular signaling and its effects on organoid symmetry breaking, crypt formation, crypt fission, and the potential compensatory cellular response to local tissue damage. Specifically, we aim to: 1. Investigate the role of spatiotemporally varying cell-matrix on real time crypt formation in intestinal organoids. 2. Iteratively pattern intestinal organoid-laden hydrogels to study the role of the ECM interactions in guiding crypt fission. and 3. Spatiotemporally regulate crypt cell composition to investigate its role in crypt fission.


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 = $534,697 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	5/7/2025	NON-COMPETING CONTINUATION	$534,697
														Subtotal = $534,697

Issue Date FY: 2024 ( Subtotal = $517,420 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	6/13/2024	NON-COMPETING CONTINUATION	$517,420
2024	2023	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	6/13/2024	COMPETING CONTINUATION	$151,316
2024	2022	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	6/13/2024	NON-COMPETING CONTINUATION	-$151,316
														Subtotal = $517,420

Issue Date FY: 2023 ( Subtotal = $574,859 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/15/2023	COMPETING CONTINUATION	$574,859
														Subtotal = $574,859

Issue Date FY: 2022 ( Subtotal = $397,109 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/23/2022	NON-COMPETING CONTINUATION	$397,109
														Subtotal = $397,109

Issue Date FY: 2021 ( Subtotal = $399,456 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/4/2021	NON-COMPETING CONTINUATION	$399,456
														Subtotal = $399,456

Issue Date FY: 2020 ( Subtotal = $401,734 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/14/2020	NON-COMPETING CONTINUATION	$401,734
														Subtotal = $401,734

Issue Date FY: 2019 ( Subtotal = $417,445 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/22/2019	NEW	$417,445
														Subtotal = $417,445

Grand Total All Awards = $3,242,720

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Photoresponsive materials to study matricellular signaling dynamics during crypt formation and fission

Award Number: R01DK120921

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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