Objectif
The insulin-linked polymorphic region (ILPR) resides in the promoter region of the gene coding for insulin (INS). This region consists of a 14-base pair tandem repeat DNA sequence of 5'-ACAGGGGTGTGGGG-3'/3'-TGTCCCCACACCCC-5' and is located 363 base pairs upstream of the transcription start site of insulin. The insulin-linked polymorphic region can form non-canonical DNA secondary structures such as G-quadruplexes, i-motifs and hairpins. Previous work at the UCL School of Pharmacy has shown that different native insulin-linked polymorphic region sequence variants form different DNA structures and these result in differences in insulin gene transcription.
This project aims to reveal insights into the relationship between different DNA sequences in the insulin promoter region, the types of non-canonical structures they form, transcription of insulin and how this is influenced by small molecule ligands. The project will use biophysical approaches to determine the structure of different sequences in the insulin promoter, cell and molecular biology to understand the effects of different sequences and structures on insulin expression, including using small molecule ligands as probes. Finally, computational biology and x-ray crystallography will be used to design improved compounds that target the insulin-linked polymorphic region and switch on insulin transcription using structure-based rational design.
Champ scientifique (EuroSciVoc)
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
- sciences naturellessciences biologiquesgénétiqueADN
- sciences naturellessciences de la Terre et sciences connexes de l'environnementgéologieminéralogiecristallographie
- sciences médicales et de la santémédecine fondamentalepharmacologie et pharmacie
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Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
WC1E 6BT London
Royaume-Uni