Wednesday, August 20, 2025 8/20/2025

The role of Tex15 in shaping stochastic olfactory receptor gene choice.

Award Number: F31DC021641
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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The role of Tex15 in shaping stochastic olfactory receptor gene choice. - PROJECT SUMMARY/ABSTRACT The incredible specificity with which we can discern a vast diversity of smells emerges from how olfactory sensory neurons (OSN) express olfactory receptor (OR) genes. These OR genes encode the proteins that bind chemical odorants. Each OSN stochastically transcribes only one allele of an OR gene. An OSN can choose to express any one of the approximately 1400 OR genes or 2800 alleles. There is no one to one relationship between an odorant and an OR as a combination of ORs are involved in the detection of one odorant. Thus, the diversity of ORs expressed is important to the main olfactory epithelium’s (MOE) ability to detect a vast range of smells. The choice of an OR gene occurs as OSN progenitors mature into an OSN. Recent work has revealed remarkable remodeling of the local chromatin and co-expression of multiple OR genes during this period, but the molecular mechanisms governing these processes and their connection to a singular OR allele expression in a mature OSN remain unknown. We show that testis expressed 15 (Tex15), a protein that has only been studied in the testes where it regulates methylation and silencing of transposons, is crucial for stochastic OR gene choice. We find that when Tex15 is knocked out there is a dramatic reduction in the diversity of expressed OR genes with a few OR genes dominating stochastic choice. Strikingly, Tex15 is only transiently expressed in OSN progenitors during a period of OR co-expression. Our central hypothesis is that Tex15 is epigenetically controlling stochastic OR gene choice, either by regulating DNA methylation or other aspects of OR gene chromatin structure. Aim 1 will determine whether Tex15 is required for transient co-expression of multiple OR genes in OSN progenitors. In aim 2, we will determine whether Tex15 protein binds to OR genes. Finally in aim 3, our experiments on primary OSNs from Tex15 null mice will determine how gene repression is mediated in OSN progenitors – through methylation or deposition of repressive heterochromatin. Together, these experiments will elucidate a novel aspect of how OSNs come to stochastically choose a single OR and how Tex15 gene and protein guides this specific yet diverse choice. We anticipate this project will uncover new and/or unexpected role for Tex15 in the MOE. This will also reveal the key molecular underpinnings for how our sense of smell develops and may provide important insight to further understand the mechanisms of smell disorder. The proposed fellowship will train this applicant in several innovative techniques in biochemical, cellular, molecular, and computational neuroscience. The established faculty-student mentorships will ensure proper scientific and professional training necessary to become a successful, independent sensory and computational neurobiologist.


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 = $40,916 )
2025	2025	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	3	7/21/2025	NON-COMPETING CONTINUATION	$40,916
														Subtotal = $40,916

Issue Date FY: 2024 ( Subtotal = $40,352 )
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	2	8/29/2024	NON-COMPETING CONTINUATION	$40,352
														Subtotal = $40,352

Issue Date FY: 2023 ( Subtotal = $39,072 )
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	001	1	8/26/2023	NEW	$0
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	1	8/26/2023	NEW	$39,072
														Subtotal = $39,072

Grand Total All Awards = $120,340

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The role of Tex15 in shaping stochastic olfactory receptor gene choice.

Award Number: F31DC021641

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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