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EU-Förderung (242.261 €): Zielsetzung der mRNA-Struktur zur Steuerung der Translation mit kleinen Molekülen Hor 27.03.2026 EU-Rahmenprogramm für Forschung und Innovation "Horizont"
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Zielsetzung der mRNA-Struktur zur Steuerung der Translation mit kleinen Molekülen
mRNAs represent a vast and underexploited space for drug discovery. As direct regulators of protein synthesis, they provide a direct conduit to function. Current efforts to target RNAs in cells with small molecules often fail to robustly yield function in a predictable manner and usually need to be tailored on a target basis. A major reason is that most approaches prioritize binding affinity over biological outcome assuming, by analogy to proteins, that tighter binding necessarily induces greater efficacy. Yet for RNA, functional output depends more on structural context, temporal accessibility, and interaction dynamics than on affinity alone. This proposal aims to discover structured, ligandable motifs in messenger RNAs (mRNAs) and to decode the mechanistic principles by which small-molecule binding can alter mRNA function. Because mRNAs control protein output directly, they offer a unique opportunity to modulate disease-relevant pathways, especially in cancers and intractable proteins. Recent unpublished work I conducted on targeting the ABL1 mRNA demonstrates this concept. We identified a functional structured element in the coding sequence of ABL1 through data-guided computational modeling. The motif we uncovered is responsive to small-molecule binding in cells. We aim to expand to other mRNAs and discover general, transferable routes to modulate translation via RNA structure. Specifically, we will focus on three interconnected aims: (1) to discover functional, structured and targetable motifs in key mRNAs, (2) to understand how small-molecule binding can be transformed into biological function, (3) to elaborate a high-throughput screening platform to efficiently explore the functional RNA-ligand chemical landscape. Establishing a rational, generalizable framework for mRNA-targeted small molecules would open new therapeutic avenues, especially for currently undruggable and orphan disease targets.
Geförderte Unternehmen:
| Firmenname | Förderungssumme |
| Centre National de la Recherche Scientifique CNRS | ? |
| Institut Curie | 242.261 € |
Quelle: https://cordis.europa.eu/project/id/101281304
Diese Bekanntmachung wurde von Englisch nach Deutsch übersetzt. Die Bekanntmachung bezieht sich auf einen vergangenen Zeitpunkt, und spiegelt nicht notwendigerweise den heutigen Stand wider. Der letzte verfügbare Stand wird auf folgender Seite wiedergegeben: Centre National de la Recherche Scientifique (CNRS), Paris, Frankreich.