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The Role of LIMA1 in the Formation of the Giant Core Actin Bundles in Tuft Cells

Award Number: F31DK141157
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025
AWARD TERMINATION DATE: 02/23/2026

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The Role of LIMA1 in the Formation of the Giant Core Actin Bundles in Tuft Cells - PROJECT SUMMARY Within the small intestinal epithelium, tuft cells are a rare chemosensory cell type (less than 1% of cells), defined by their unique morphology consisting of large apical protrusions that extend over 2 μm into the lumen. Tuft cells have been implicated in sensing intestinal parasites and activating an immune response and are therefore recognized for their importance in maintaining the health of the intestinal epithelium. Tuft cell morphology is defined by a unique cytoskeletal structure consisting of giant bundles of actin filaments, which support an array of large apical membrane protrusions (a “tuft”) while extending over 6 μm down into the cell’s perinuclear region. Despite their role in activating an immune response against intestinal parasites, tuft cells remain understudied due to their rarity in the intestinal epithelium. As a result, there is a gap in our understanding of how the unique cytoskeletal architecture found in tuft cells contributes to the physiological function of this cell type. My preliminary research identified LIM domain and actin binding 1 (LIMA1) as a tuft cell enriched factor that localizes specifically to the basal ends of core actin bundles that extend deep into the sub-apical cytoplasm. Previous studies indicate that LIMA1 can cross-link actin, inhibit actin depolymerization, and inhibit actin branching in vitro, which are all molecular activates that tuft cells could use to promote the formation of giant actin bundles. Based on my preliminary data and previous studies in the literature, I hypothesize that LIMA1 drives the formation of the giant actin bundles found in tuft cells. Under Aim 1, I will test this hypothesis by establishing how LIMA1 expression impacts the formation of actin bundles in an intestinal cell culture model. In addition, I will use live cell imaging and Fluorescence Recovery After Photobleaching (FRAP) to characterize LIMA1 dynamics on actin bundles and determine if LIMA1 expression impacts the dynamics of actin turnover in decorated bundles. In Aim 2, I will determine whether LIMA1 expression is required for tuft cell actin bundle formation. Because tuft cells are not represented in intestinal epithelial cell culture models, I will instead use a LIMA1 knockout mouse model and visualize de novo tuft cell development in the context of intestinal organoids derived from these animals. This research seeks to develop a fundamental understanding of the molecular machinery underpinning the unique morphology of tuft cell. The insights derived from this project will additionally help us understand how tuft cells contribute to gastrointestinal physiology, immune sensing, and human health issues caused by intestinal parasites and for inflammatory illnesses such as Crohn’s Disease.


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: 2027 ( Subtotal = -$784 )
2027	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	10/27/2026	NON-COMPETING CONTINUATION	-$784
														Subtotal = -$784

Issue Date FY: 2026 ( Subtotal = -$19,168 )
2026	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/23/2026	TERMINATION	-$19,168
														Subtotal = -$19,168

Issue Date FY: 2025 ( Subtotal = $34,878 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/4/2025	NON-COMPETING CONTINUATION	$34,878
														Subtotal = $34,878

Issue Date FY: 2024 ( Subtotal = $34,314 )
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/8/2024	NEW	$34,314
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	7/8/2024	NEW	$0
														Subtotal = $34,314

Grand Total All Awards = $49,240

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The Role of LIMA1 in the Formation of the Giant Core Actin Bundles in Tuft Cells

Award Number: F31DK141157

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

AWARD TERMINATION DATE: 02/23/2026

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