Charting the translational landscape of early development

This is the project summary of my ERC starting grant: The biogenesis of proteins transitions through two main phases: transcription and translation. While transcription has been extensively studied, both at the individual gene-level and genome-wide, translation has only recently been explored by high-throughput methods. Since translation has been shown to be more predictive of the protein content than the abundance of mRNA the study of translational control is arguably as important as the study of transcription. It is increasingly becoming clear that translation itself is under tight regulation and that the factors modulating protein synthesis may differ between tissues. A comprehensive understanding of what determines translational efficiency in a given tissue and time point is therefore imperative to our understanding of gene regulation. Recently, evidence from zebrafish has emerged that during embryogenesis there is a major switch in translational programs coinciding with the transition from a maternal to a zygotic transcriptome. It is not known what triggers the switch and what determines translational efficiency after the switch. This project aims to characterize this and other translational programs in an integrated genome-wide manner. In particular, we will use the developing zebrafish as a model system to 1) identify factors involved in the switch from a maternal to a zygotic translational program, and 2) generalize 1) to the whole organism and identify tissue-specific translational programs and their factors. Ultimately, understanding translational regulation is necessary for a comprehensive understanding of gene regulation. The outlined project will provide new insight into the regulation of translational specialization and its effects. In addition to providing new biological insights, this project will also develop open source tools that will facilitate the analysis of high-throughput translation assays for the scientific community.