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Determining the mechanism and impact of streptococcal RaS-RiPPs on the human oral microbiome

Award Number: R00DE032311
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/16/2024
PERIOD OF PERFORMANCE END DATE: 08/15/2027

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Determining the mechanism and impact of streptococcal RaS-RiPPs on the human oral microbiome - PROJECT SUMMARY The human oral microbiome is home to a unique group of bacteria with the ability to affect the overall health of the human host: Streptococci spp. This group is involved in a wide range of diseases, from dental caries to infective endocarditis. They include important oral pathogens such as the cariogenic Streptococcus mutans and commensal organisms such as Streptococcus mitis. These important oral members produce a large array of radical-S-adenosylmethionine ribosomally synthesized and post-translationally modified peptides (RaS-RiPPs). The newly identified compounds include a wealth of chemical structures and have been found to inhibit the growth of other oral Streptococci, as well as modulate the behavior of producer organisms themselves. The initial goal of this proposal is to elucidate the mechanism of action of the RaS-RiPP tryglysin from S. mutans, and to examine its impact on the functional oral microbiome. Upon defining tryglysin’s mechanism of action on oral Streptococci and the oral microbiome, this study will be expanded to examine the biological significance of other RaS-RiPPs produced by Streptococci: streptosactin, suisactin, rotapeptides, and NxxC family peptides. While the chemical structure and synthesis of these peptides has been defined, the biological significance of these identified RaS-RiPPs is unexplored. Given the important status of Streptococci spp. to the health of the human oral microbiota, this represents a major gap in knowledge about a class of peptides with huge potential impacts on overall oral health. This proposal aims to create a research platform for studying RaS-RiPPs from oral Streptococci, defining their function, and examining shifts in the functional oral microbiome in response to their production. Executing this research program at the University of Illinois at Chicago (UIC) will allow for the establishment of the candidate as an independent researcher and provide avenues for the achievement of the candidate’s career goals: establishing a productive and first-rate research laboratory and securing a tenured faculty position at a major research institution.


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 = $249,000 )
2025	2025	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Oral Diseases and Disorders Research	000	3	7/10/2025	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Oral Diseases and Disorders Research	000	2	9/10/2024	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $498,000

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Determining the mechanism and impact of streptococcal RaS-RiPPs on the human oral microbiome

Award Number: R00DE032311

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/16/2024

PERIOD OF PERFORMANCE END DATE: 08/15/2027

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