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Functional analysis of ribosome heterogeneity during zebrafish embryogenesis

Project description

Ribosome heterogeneity during zebrafish embryogenesis

Embryogenesis involves coordinated changes in gene expression at transcriptional and translational levels. In zebrafish, translation at early stages of embryo development relies on maternal, oocyte-derived ribosomes which are completely replaced by newly synthesised somatic ribosomes within five days after fertilisation. The EU-funded RiboHeterogeneity project will investigate the regulatory potential of maternal and somatic ribosomes during zebrafish embryogenesis. The research will analyse the translational activities of maternal and somatic ribosomes, substrate specificity, mRNA sequence and length, the kinetics of translation and the regulation of ribosomal degradation during embryogenesis. The results of the project have the potential to reveal novel regulatory mechanisms of vertebrate embryogenesis and will shed light on the functional significance of heterogeneous ribosomes.

Objective

The process of embryogenesis involves coordinated changes in gene expression at both transcriptional and translational levels. In zebrafish, translation at early stages of embryo development relies on maternal, oocyte-derived ribosomes which are completely replaced by newly synthesized somatic ribosomes within 5 days after fertilization. Strikingly, preliminary data obtained in the Pauli lab suggest that maternal and somatic ribosomes diverge not only in rRNA content but also in protein composition and structure. Despite their heterogeneity, potential differences in the function of maternal and somatic ribosomes remain unknown. The dual ribosomal system present in zebrafish embryos thus provides a unique, powerful tool to address the controversial idea regarding the existence of ‘specialized ribosomes’ having distinct functions in translation.

In the proposed research project, I will investigate the regulatory potential of maternal and somatic ribosomes during zebrafish embryogenesis. To this end, I will analyze the translational activities of maternal and somatic ribosomes by determining substrate specificity, preferred mRNA features (sequence and length) and kinetics of translation. In addition, I will study the regulation of ribosomal degradation during embryogenesis in order to understand how and why the maternal ribosomal machinery is turned-over despite the high energy cost associated with making a new set of ribosomes. To accomplish these aims, I will combine diverse state-of-the-art methodologies, including in vivo and in vitro translation assays, biochemical ribosome purification techniques, SLAM-seq, and molecular and genetic studies in zebrafish. The results obtained have the potential to reveal novel regulatory mechanisms acting during vertebrate embryogenesis and will help to pinpoint the functional significance of heterogeneous ribosomes.

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-2019

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Coordinator

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Net EU contribution
€ 174 167,04
Address
CAMPUS-VIENNA-BIOCENTER 1
1030 Wien
Austria
Region
Ostösterreich Wien Wien
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost
€ 174 167,04