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Visualisation of translation initiation reaction on single mRNA molecules in vivo

Project description

Imaging RNA protein interactions in cells

Protein synthesis commences with the binding of key initiation factors to mRNA molecules and ribosomes in a process known as translation initiation. Despite its importance in gene expression regulation, little is known about the underlying dynamics of translation initiation. To address this issue, the EU-funded smTI project plans to develop a single-molecule imaging method applicable to live cells. This method will help to visualise in real-time the binding and release of eukaryotic initiation factors, eIFs and ribosomal subunits on mRNA molecules. Results will unveil important aspects of protein synthesis regulation in health and disease.

Objective

Translation initiation is a key step in the regulation of protein synthesis and is regulated by at least 12 different initiation factors in eukaryotes (eIFs). However, the underlying dynamics of this process remain unclear. I propose to develop a single-molecule live-cell imaging method that can be broadly applied to study the dynamics of translation initiation on individual mRNAs in human cells. The aim of the project is to visualise the binding and release of eIFs and ribosomal subunits on single mRNA molecules in real-time during translation initiation. This method, combined with imaging the synthesis of a nascent polypeptide on a single mRNA, will address the role of dynamic eIFs assembly in heterogeneous mRNA translation events, such as translational bursting and start site selection. The project will uncover the real-time dynamics of translation initiation, reveal the key mechanism of translation regulation, and provide a powerful and generally applicable method to study translation initiation and other RNA-binding protein interactions with mRNAs. The project will be developed with a leading research group for translation imaging. I introduce single-molecule imaging techniques that would facilitate new research in the group and enable transfer of ideas. The project will expand my research experience, skills, and professional networks, thereby enhancing my career development as an independent researcher.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2020

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Coordinator

KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW
Net EU contribution
€ 187 572,48
Address
KLOVENIERSBURGWAL 29 HET TRIPPENHUIS
1011 JV AMSTERDAM
Netherlands
Activity type
Research Organisations
Links
Total cost
€ 187 572,48