Project description
Novel sequencing methods to study translation machinery in single cells
Recent developments in novel single-cell sequencing methods made possible the quantification and analysis of the transcriptomes in millions of individual cells. On the contrary, no current methods allow the evaluation of translation efficiencies in single cells and their correlation with the tRNA levels and modifications, including RNA-bound proteins and RNA methylation. The EU-funded scTranslatomics project aims to develop innovative technologies that will enable the investigation of translation and translation regulatory mechanisms at single-cell resolution. The novel multi-omics approaches to quantify and evaluate translation in single cells will provide information about ribosome position along the transcript, the RNA methylation status of the transcript, RNA-bound proteins, tRNA expression levels and modifications.
Objective
In recent years novel single-cell sequencing methods have allowed an in-depth analysis of the diversity of cell types and states in a wide range of organisms. Due to the continuous optimization of experimental and computational methods by many research groups, it is now possible to sequence the transcriptomes of thousands to millions of individual cells. Albeit an exciting development, transcription only covers the first step in the central dogma. The second step, the process of translation, is currently much harder to explore in single cells. Building upon existing ribosome profiling protocols, our laboratory recently majorly increased the sensitivity of these assays allowing ribosome profiling in single cells. However, currently no methods exist to determine the translation efficiencies in single cells and to correlate translation efficiencies to tRNA levels and their modifications, RNA bound proteins, and m6A methylation of mRNA, all major regulatory mechanisms of translation. The overarching goal of this proposal is to develop several novel multi-omics approaches to quantify translation in single cells by integrating information on ribosome position along the transcript, tRNA expression levels, tRNA modifications, RNA-bound proteins, and the m6A methylation status of the transcript. These technologies will open novel avenues to start exploring translation and its regulatory mechanisms with single-cell resolution. Whereas major discoveries have been made during the last decade by exploring the genome, the epigenome, and the transcriptome using single-cell sequencing approaches, translation, the major second step in the central dogma, is still very much unexplored at the single-cell level. I hope that the tools, presented in this proposal will provide the community with methods to explore, and ultimately understand, how translation contributes to the astonishing heterogeneity among single cells.
Fields of science (EuroSciVoc)
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This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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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.
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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-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2021-ADG
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1011 JV AMSTERDAM
Netherlands
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