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Understanding the Roles of Glycosylated RNA Species in Homeostasis and Human Disease

Award Number: F32GM167207
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2026
PERIOD OF PERFORMANCE END DATE: 09/29/2029

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Understanding the Roles of Glycosylated RNA Species in Homeostasis and Human Disease - PROJECT SUMMARY ABSTRACT In 2021, Flynn et al. reported the existence of glycosylated RNAs (glycoRNAs), small RNA species decorated with glycans and localized on the surface of many mammalian cell types — a paradigm-challenging discovery which bridged the previously distinct scientific realms of RNA and glycoconjugates. Follow-up investigations into the nature of glycoRNAs revealed that their expression is dynamically regulated, fluctuating during immune activation and cancer progression, demonstrating the importance of glycoRNAs in human health and disease biology. However, the mechanistic determinants of these emerging glycoRNA functions remain elusive, in large part due to limitations of existing investigative techniques, which generally allow only blanket identification of glycoRNA species. We propose to leverage advances in AI-based protein design for the creation of de novo protein binders as molecular tools for the precisely targeted investigation of glycoRNAs and their interactions with native cellular machinery. We will first develop miniprotein binders against multiple epitopes of known endogenous glycoRNA-interacting proteins to identify critical interfaces for binding and cellular trafficking of glycoRNAs. We will design ultraspecific de novo glycoRNA binders based on our findings and employ them to investigate sequence- and glycan-specific interactions with cellular pathways. Finally, we will blockade protein- glycoRNA interactions in cellulo using our de novo binders to investigate the roles of glycoRNA in homeostasis and disease progression with unprecedented specificity. By using these tools to investigate these mysterious biomolecules and their interactions with native cellular machinery, we will deepen the field’s understanding of glycoRNAs and uncover potential avenues for disease diagnosis, prevention, and treatment.


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 = $76,300 )
2026	2026	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	001	1	9/9/2026	NEW	$0
2026	2026	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	1	9/9/2026	NEW	$76,300
														Subtotal = $76,300

Grand Total All Awards = $76,300

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Understanding the Roles of Glycosylated RNA Species in Homeostasis and Human Disease

Award Number: F32GM167207

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2026

PERIOD OF PERFORMANCE END DATE: 09/29/2029

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