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Selective aptamer probe for detecting and targeting multimolecular G-quadriplexes aggregates in amyotrophic lateral sclerosis (ALS) disease

Project description

Molecular insight into specialised genomic structures

Parts of the genome, such as telomeres and gene promoters rich in guanine bases, deviate from the usual double helix conformation. Instead, four guanine bases interact to form G-quadruplexs (G4s), square-shaped structures that fold back into a knot. This stable conformation influences important cellular functions, including gene expression and response to stress. With the support of the Marie Skłodowska-Curie Actions programme, the SPOTTER project focuses on multimolecular G4s (mG4s) that involve multiple DNA strands. Researchers aim to develop the first selective probe designed to recognise only mG4s. This aptamer-based tool will enable live-cell imaging and genome-wide mapping of mG4s, providing new insights into their functions

Objective

G-quadruplex structures (G4s) are gaining attention due to their widespread presence in the human genome, featuring over 700,000 identified sequences. These stable G4s are often found in critical areas of our DNA, such as telomeres, gene promoters, and regions linked to repeat expansions in diseases.

However, when investigating their biological function, multimolecular G-quadruplexes (mG4s) have been often overlooked and deemed unlikely to be physiologically relevant, with the bulk of recent advances on G4-biology almost exclusively focused on unimolecular G-quadriplexes (uG4s).

SPOTTER aims to fill this critical gap in the biology of mG4, by generating a selective probe that is currently missing to study these structures. Specifically, in this proposal, an aptamer-based probe that can be tuned to interact exclusively with mG4s will be developed.This tool will facilitate live-cell imaging and genome-wide mapping of mG4s for the very first time.

This will further allow me to explore the role of mG4 formed in guanine-rich RNA repeat expansions, which could trigger formation of insoluble aggregates that are relevant to neurodegenerative diseases, such as in amyotrophic lateral sclerosis (ALS).

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

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

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Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Net EU contribution
€ 260 347,92
Address
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ London
United Kingdom
Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Total cost
No data