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Visualizing splicing dynamics in human cells by cryo-ET

Project description

Decoding gene regulation

During RNA transcription of coding genes, the initial RNA molecules include non-coding segments known as introns. These sequences must be removed to generate mature messenger RNA (mRNA) suitable for protein synthesis, a process carried out through splicing. RNA splicing is mediated by the spliceosome, a complex and dynamic assembly of proteins and RNAs. Although considerable research has been devoted to understanding the spliceosome, its precise behaviour within living cells remains elusive. With the support of the Marie Skłodowska-Curie Actions programme, the SpliceTomo project seeks to capture the spliceosome in action within the cell nucleus. To achieve this, researchers will use cutting-edge imaging techniques, including cryo-electron tomography, to deepen our understanding of gene regulation in health and disease.

Objective

The spliceosome is a dynamic, multicomponent macromolecular complex essential for the precise removal of introns from pre-mRNA. While extensive genetical, biochemical, and structural studies have provided insights into the splicing cycle, the structural dynamics and distribution of spliceosomes within human cells remain only partially understood. In this project, I aim to study the in situ structures of the spliceosome by cryo-electron tomography (cryo-ET) and sub-tomogram averaging, alongside other advanced techniques, to elucidate the dynamic assembly and spatiotemporal distribution of spliceosome, as well as its crosstalks with other nuclear machinery. This research aims to visualize macromolecular complexes in their native environments at near-atomic resolution in the nucleus, providing new insights into the mechanisms of pre-mRNA splicing in human cells.

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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

EUROPEAN MOLECULAR BIOLOGY LABORATORY
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.

€ 242 260,56
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost

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