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Illuminating the secretome: a protein tagging resource

Award Number: R24OD038113
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Illuminating the secretome: a protein tagging resource - SUMMARY Aberrant expression and secretion of proteins in the secretome have been linked to numerous diseases. Nematode secretomes are of additional significance as they mediate interactions with host tissues and present opportunities to discover novel immunomodulatory compounds. Although secretome proteins are enriched for drug targets and biomarkers for disease and aging, the gap in knowledge concerning the in vivo distribution of secreted proteins is a barrier to leveraging and contextualizing information we have so far to fully understand their biological function. To address this gap, we will create a resource of genetic stocks expressing endogenously tagged secretome proteins using a highly tractable model organism, the nematode C. elegans. We and others have established the feasibility and utility of large-scale tagging of secreted extracellular matrix proteins by fluorescent protein and affinity tags. A hallmark of our approach is the use of ‘knock-in’ editing of endogenous genes, to avoid mis/over-expression and to allow generation of stable genetic strains that allow reproducible and comparable analysis of expression patterns. We will prioritize 1000 high-value genes of widest interest to the biomedical community. This target set will include 410 secretome proteins with orthologs implicated in human diseases, aging, or proteostasis; 320 proteins prominent in excretory-secretory product (ESP) proteomics or innate immune roles; and 270 representatives of conserved secretome protein families and proteins secreted by unconventional secretory pathways. We have our initial list of 1000 targets and will prioritize select targets based on input from the C. elegans and broader scientific community. Secretome genes will also be curated using structure-based tools to classify proteins currently un-annotated based on primary sequence. Genetically tagged, stable knock-in stocks will be deposited in the stock center (CGC) for distribution as soon as they are validated, and molecular or expression information made available on CGC and WormBase databases as well as a UCSC-hosted website. In addition to the overarching goal of generating validated and curated knock-in strains, related technical and scientific aims will be pursued, and gene editing technology will be further optimized to enhance the value of the resource. As the secretome is enriched in small proteins (<200 amino acids), methods for tagging small proteins will also be developed. The precise localization of a subset of tagged proteins will be characterized in vivo at high resolution, to launch a draft Secretome Atlas. Our proposed resource will strongly leverage the tractability of protein tagging in C. elegans to deliver novel biological insights into the secretome. The results of this project will benefit multiple communities of funded researchers with interests in secreted extracellular proteins, both those using C. elegans and other organisms.


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 = $790,502 )
2026	2026	UNIVERSITY OF CALIFORNIA SANTA CRUZ	1156 HIGH ST	SANTA CRUZ	CA	95064	SANTA CRUZ	USA	Research Infrastructure Programs	000	1	6/8/2026	NEW	$790,502
														Subtotal = $790,502

Grand Total All Awards = $790,502

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Illuminating the secretome: a protein tagging resource

Award Number: R24OD038113

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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