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Investigating the role of RNA helicase DHX36 in modulating aberrant RNA condensation

Award Number: F32GM161082
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/22/2025
PERIOD OF PERFORMANCE END DATE: 09/21/2027

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Investigating the role of RNA helicase DHX36 in modulating aberrant RNA condensation - Project Summary Stress granules (SGs) are transient cytoplasmic ribonucleoprotein (RNP) granules formed in response to cellular stress. SGs play crucial roles in regulating RNA metabolism and promoting cell survival, but their persistence can be cytotoxic and contribute to neurodegenerative diseases. Stable RNA G-quadruplex structures (rGQs) are involved in SG formation and can inﬂuence their biophysical properties to form either liquid- or solid-like assemblies. Hence, aberrant accumulation of rGQs can compromise SG dissolution upon removing stress, resulting in SG persistence. The primary focus of this application is to investigate how the RNA helicase DHX36, known for its ability to remodel rGQs, inﬂuences SG dissolution and aging dynamics. The proposal is structured around three speciﬁc aims. Aim 1 will examine how altering DHX36 levels and perturbing its ATP/RNA binding ability aﬀects SG aging dynamics, with a hypothesis that DHX36-mediated remodeling of rGQs in SGs is necessary for maintaining the ﬂuidity of SGs and preventing their transition to solid-like, potentially harmful states. Using live-cell imaging and quantitative biophysical methods, we will track SG disassembly kinetics following stress exposure and DHX36 manipulation. Aim 2 focuses on understanding how DHX36 aﬀects SG biophysical properties and aging dynamics, by employing optical tweezer-based nano-rheology approaches in an in vitro lysate-based stress granule system. Aim 3 will assess DHX36’s ability to remodel aberrant RNA condensation, particularly in the context of neurological diseases such as ALS, where repeat expansion RNAs form toxic condensates. Using bottom-up reconstitution of RNP condensates, this aim will test a hypothesis that DHX36 can chaperone intra-condensate liquid-to-solid phase transitions of repeat RNAs. By combining innovative biochemical, biophysical, and live-cell imaging approaches, this research aims to provide novel insights into the cellular mechanisms that regulate SG dynamics and RNA condensation. The ﬁndings could have broad implications for understanding RNP granule aging and may lead to potential therapeutic strategies for neurodegenerative disorders associated with aberrant RNP granules. The fellowship will be conducted at the University of Buﬀalo in the laboratory of Dr. Priya Banerjee, a leading researcher in the biophysics and biology of RNA-protein phase separation. This environment provides access to cutting-edge biophysical tools and a collaborative, interdisciplinary training environment, ensuring comprehensive preparation for an independent research career.


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 = $86,930 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	000	1	9/2/2025	NEW	$86,930
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	001	1	9/2/2025	NEW	$0
														Subtotal = $86,930

Grand Total All Awards = $86,930

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Investigating the role of RNA helicase DHX36 in modulating aberrant RNA condensation

Award Number: F32GM161082

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/22/2025

PERIOD OF PERFORMANCE END DATE: 09/21/2027

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