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QDHassay

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In vitro and In-cell characterization of Quadruplex-duplex hybrids: conformation...

In vitro and In-cell characterization of Quadruplex-duplex hybrids: conformation, folding, and recognition by drug-like ligand molecule "Nucleic acids are intrinsically polymorphic. Apart from the Watson-crick duplex, guanine-rich sequences can form G-quadruplex (G4) structures, which have become attractive targets for small molecule ligands. It is now proven tha... ver más

31/07/2024

166K€

Presupuesto del proyecto: 166K€

Líder del proyecto

Masarykova univerzita No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-07-31

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

HORIZON-WIDERA-2022-TALENTS-02-01: Fostering balanced brain circulation – ERA Fellowships

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166.28K€ | Lider

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Últimas noticias

01-12-2024: REDES En las últimas 48 horas el Organismo REDES ha otorgado 1337 concesiones

01-12-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

01-12-2024: AEI En las últimas 48 horas el Organismo AEI ha otorgado 23 concesiones

Duración del proyecto: 25 meses Fecha Inicio: 2022-06-12
Fecha Fin: 2024-07-31

Líder del proyecto

Masarykova univerzita

TRL 4-5

Presupuesto del proyecto 166K€

Descripción del proyecto "Nucleic acids are intrinsically polymorphic. Apart from the Watson-crick duplex, guanine-rich sequences can form G-quadruplex (G4) structures, which have become attractive targets for small molecule ligands. It is now proven that G-quadruplexes can form in cells. Today most biophysical and structural/ligand binding studies are carried out in dilute aqueous solutions and the presence of artificial crowding agents/cosolvents. Still, recent works suggest that the folding of G4s may differ in the cellular milieu context due to the agents' limitations. Thus there is an immense need for in-cell-based structural biology approaches. In the proposal, I aim to address critical milestones leading to the bioactive conformation inside the cell and the development of effective/specific G4 targeting drugs using an essential sub-class of G4 structures as a paradigm, namely quadruplex−duplex hybrids (QDH-hereafter). We will focus on low- and high-resolution spectroscopic approaches and mass spectrometry-based ligand screening assays characterizing ligand-QDH interaction. On the methodological part, we will develop in-cell NMR in ""native"" conditions (starting from unfolded conformation: denovo folding) and propose a ligand screening assay inside the cellular system. Our project will contribute to unveil fundamental principles of nucleic acid folding. It will also foster collaboration between two European institutes specialized in complementary biophysical and structural approaches to study biomolecular folding. In a nutshell, the Maria Skłodowska Curie fellowship will flourish my scientific excellence and the resilience needed for my original ideas to become a reality and communication and public engagement skills across cultures and disciplines."

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