Innovating Works

RNPdynamics

Financiado
Multivalent interactions driving RNP dynamics in development and disease
Ribonucleoprotein complexes (RNPs) play many key regulatory roles in development. Moreover, mutations causing cancer or neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), often occur in RNA-binding proteins (... Ribonucleoprotein complexes (RNPs) play many key regulatory roles in development. Moreover, mutations causing cancer or neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), often occur in RNA-binding proteins (RBPs). These mutations are concentrated in the intrinsically disordered regions (IDRs), which play a central role in the control of RNP assembly and disassembly. RNP dynamics is often driven by multivalent interactions that are mediated by multiple elements within IDRs of RBPs, which can condense the RNP such that it separates from the surrounding liquid through the phenomenon of liquid-liquid phase separation. Transcriptomic insights into the physiological functions of such multivalent RNP assembly are needed to understand their regulation, or deregulation through disease-causing mutations. Here, we will build a framework of experimental and computational methods to study the mechanisms by which the dynamic multivalent interactions drive RNP remodelling, and how such RNP dynamics contributes to cellular transitions in development and disease. The first objective will be to identify the functions of specific RBPs in cell-state transitions during neuronal differentiation, and the mechanisms of IDR-mediated multivalent interactions in these functions. The next objective will be to establish new tools to manipulate RNP assembly through multivalent RNA binding sites and IDRs. Finally, the new insights and tools will be integrated with the goal to fine-tune the RNP assembly of ALS-mutant RBPs, and thereby ameliorate their toxicity. ver más
30/09/2025
NIC
2M€
Duración del proyecto: 69 meses Fecha Inicio: 2019-12-02
Fecha Fin: 2025-09-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2019-12-02
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2018-ADG: ERC Advanced Grant
Cerrada hace 6 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
KEMIJSKI INSTITUT No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5