Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- medical and health sciencesbasic medicinepharmacology and pharmacy
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
WC1E 6BT London
United Kingdom