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Investigating the chromatin landscape of complex tissues through cell-type-specific patterns

Award Number: F32GM153148
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Investigating the chromatin landscape of complex tissues through cell-type-specific patterns - Project Summary/Abstract The long-term objectives of this proposal include the following: 1) to generate cell-type- specific chromatin profiles of the four cell types of the intestine, 2) to identify the effect crippled silencing in intestinal stem cells has on progenitor cells, and 3) to characterize the transcriptional changes associated with an age-related increase in the Polycomb Repressive Complex-2 mark, H3K27me2, in the intestine. Cell-type-specific chromatin profiles aid the specific gene expression patterns necessary for the function and identity of the cell. Complex tissues are comprised of both stem and differentiated cells with different phenotypes, transcriptional profiles, and roles within the tissue. The intestine contains a population of stem cells responsible for replenishing damaged cells from the multiple stimuli exerted on the intestine throughout the organism’s life span. However, the determining factors, especially at the chromatin level, that make each cell type unique are unknown. Investigation into the chromatin modifications of each cell type will provide insight into the unique roles each cell plays in the function of the tissue. To generate gut cell-specific chromatin profiles, I will use CUT&Tag, a robust and sensitive chromatin profiling technique that can be used with low cell numbers. I will generate landscapes for chromatin modifications for all cell types of the gut to comprehensively profile the epigenetic state of this tissue. Because of the importance of silencing modifications for cellular identity and previous observations of loss of chromatin silencing affecting the gut cells, I will investigate the effect of the loss of different chromatin silencing pathways in intestinal stem cells on progenitor cells. Since the intestinal stem cells are the only mitotically active cells in the intestine and the source of all other cells in the gut, their chromatin profiles likely affect the progenitor cells. Additionally, observations of age-related increases in H3K27me2 in the Drosophila melanogaster gut may indicate the protective role H3K27me2 has in preventing pervasive transcription as tissue ages. The insights gained from this project will help us understand the cell-type-specific chromatin profiles of cells of complex tissue and how chromatin modification changes in stem cells affect their progenitors. My proposed project fits the mission of NIGMS to fund research in fundamental biology that increases understanding of the principles that underlie biological processes.


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 = $79,348 )
2026	2026	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	001	3	3/27/2026	NON-COMPETING CONTINUATION	$1,308
2026	2026	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	000	3	1/19/2026	NON-COMPETING CONTINUATION	$78,040
														Subtotal = $79,348

Issue Date FY: 2025 ( Subtotal = $75,520 )
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	001	2	6/13/2025	NON-COMPETING CONTINUATION	$1,236
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	000	2	12/23/2024	NON-COMPETING CONTINUATION	$74,284
														Subtotal = $75,520

Issue Date FY: 2024 ( Subtotal = $73,828 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	003	1	5/21/2024	NEW	$4,748
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	001	1	12/19/2023	NEW	$0
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	002	1	12/19/2023	NEW	$0
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Biomedical Research and Research Training	000	1	12/19/2023	NEW	$69,080
														Subtotal = $73,828

Grand Total All Awards = $228,696

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Investigating the chromatin landscape of complex tissues through cell-type-specific patterns

Award Number: F32GM153148

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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