Spatiotemporal dynamics of dsRNA-protein associations throughout C. elegans development

NIH RePORTER · NIH · F32 · $74,284 · view on reporter.nih.gov ↗

Abstract

Project Summary Double-stranded RNA (dsRNA) structures are abundant in the nucleus and have been implicated in various diseases, such as autoimmune disorders, cancers, and neurological conditions like epilepsy and Alzheimer's. However, their functional role in RNA biology remains poorly understood, representing a significant gap in our knowledge. Our project aims to investigate the hypothesis that dsRNA presents a unique substrate in nascent transcripts, acting as a nucleation site for context-specific functional protein complex formation. Building on the Bass Lab's previous findings that dsRNAs are highly expressed in essential genes embedded in heterochromatin and enriched in embryos and neurons, we will employ computational approaches, including thermodynamics and machine learning, to identify high-confidence dsRNA-forming sequences and analyze their spatiotemporal expression patterns throughout C. elegans development. In the next phase of our project, we will explore the direct interaction of dsRNA binding proteins and the potential roles of secondary interacting proteins in forming diverse double-stranded ribonucleoprotein complexes using the J2 antibody and TurboID-based proteomics. This research will be conducted at the University of Utah Medical School under the mentorship of Distinguished Professor Brenda Bass, who has extensive experience in training independent scientists in biochemistry and molecular biology. The Bass Lab, within the Department of Biochemistry, provides the necessary resources and environment for successful postdoctoral training and project completion.

Key facts

NIH application ID
10826165
Project number
1F32GM153132-01
Recipient
UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
Principal Investigator
Ryan John Andrews
Activity code
F32
Funding institute
NIH
Fiscal year
2024
Award amount
$74,284
Award type
1
Project period
2024-02-01 → 2025-01-31