Project description
Molecular insight into mRNA export and gene expression regulation
The export of mRNA from the nucleus to the cytoplasm is crucial in gene expression, ensuring only fully processed mRNAs reach the cytoplasm, while unprocessed RNAs are degraded. Although this selective export is believed to involve export factors that package mature mRNA, many aspects in the process remain poorly understood, including the specific proteins involved. With the support of the Marie Skłodowska-Curie Actions programme, the mRNApackex project aims to identify and characterise proteins implicated in nuclear mRNA export. Detailed characterisation of these promising candidate proteins will provide new insights into the mechanisms of mRNA packaging and the regulation of gene expression.
Objective
The export of mRNA from the nucleus to the cytoplasm is an essential step in eukaryotic gene expression. This process requires that only fully processed mRNAs are exported, while undesirable RNAs are degraded in the nucleus. This selectivity is proposed to be mediated by the packaging of mature mRNA by export factors, protecting mRNA from nuclear degradation and licensing it for export to the cytoplasm. However, this model has not been directly and thoroughly tested. Furthermore, the full range of factors that promote the selective packaging and export of mRNA is not yet known.
In this proposal, I propose an interdisciplinary and collaborative project that addresses these two major outstanding topics in gene expression. To address the role of mRNA packaging as a key driver of nuclear export versus degradation, I propose to employ a time-resolved transcriptomics and modeling approach to simultaneously measure nuclear mRNA export and degradation rates, modulating mRNA compaction state with rapid protein degradation. Next, I will employ ORF-tag, a novel genome-wide gain-of-function screening method that will determine the full list of proteins sufficient to drive nuclear mRNA export. I will then characterize promising novel export factors using transcriptomic and biochemical approaches to integrate these proteins into our structural understanding of nuclear mRNA packaging.
The diverse methodology of this project, the technical support both within the host labs and the facilities on campus, and the high quality of training resources and supervision available will facilitate my own development as a scientist and prepare me perfectly to establish my own independent research group. Through my relocation from the UK to Austria, I will expand the European RNA biology network, forging future international collaborations. My background in molecular and computational biology will allow me to execute this impactful project and answer fundamental questions in gene expression.
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Keywords
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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1030 Wien
Austria
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