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The Role of Non-Canonical DNA Structures in Insulin Expression

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.

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Topic(s)

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

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITY COLLEGE LONDON
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
GOWER STREET
WC1E 6BT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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