In vitro and In-cell characterization of Quadruplex-duplex hybrids: conformation, folding, and recognition by drug-like ligand molecule

Información del proyecto

QDHassay

Identificador del acuerdo de subvención: 101090333

DOI

10.3030/101090333

Proyecto finalizado el 31 Agosto 2022

Fecha de la firma de la CE 12 Junio 2022

Fecha de inicio 1 Agosto 2022

Fecha de finalización 31 Julio 2024

Financiado con arreglo a

• Widening participation and spreading excellence

Coste total

Sin datos

Aportación de la UE

€ 166 278,72

Coordinado por

Masarykova univerzita
Czechia

Objetivo

"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 quadruplexduplex 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 Skodowska 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."

Palabras clave

• NMR
• In-cell NMR
• Nucleic acids
• Quadruplex-duplex hybrid
• DNA-drug interaction

Programa(s)

• HORIZON.4.1 - Widening participation and spreading excellence PROGRAMA PRINCIPAL
  
• HORIZON.4.1.5 - Fostering brain circulation of researchers and excellence initiatives
  

Tema(s)

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

Régimen de financiación

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

Convocatoria de propuestas

HORIZON-WIDERA-2022-TALENTS-02

Coordinador

Masarykova univerzita

• Aportación neta de la UEn: € 166 278,72
• Dirección: Zerotinovo namesti 9 ; 601 77 Brno ; Chequia
• Región: Česko › Jihovýchod › Jihomoravský kraj
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: Sin datos