Translational control through tRNA thiolation: data analysis and experiments

Studying the dynamics and regulation of mRNA translation by ribosomes provides insights into the regulation of cellular mechanisms. Using ribo-seq data it is possible to quantify and determine the role played by translation in the control of gene expression. The characterization of the ultimate mechanisms causing differences in the translation behavior is a matter of intensive study. Especially in recent years tRNA modifications by thiolation of bases at the wobble position revealed that they are involved in determining the accuracy of the genetic code by enhancing aminoacylation kinetics, assisting proper codon-anticodon pairing and by preventing frameshifting during translation

In this project you will first computationally analyze available ribo-seq data for E. coli to discover the set of genes for which stress conditions are likely to produce the most reproducible effects. In a second part of the project, you will perform experiments aimed at verifying the hypothesis that tRNA thiolation affects translation efficiency by measuring variations in the resulting ribo-seq data to uncover significant changes in the dynamics of translation. Thirdly, you will analyze the ribo-seq profiles resulting from database and experimentally derived data using advanced statistical and machine learning methods to gain crucial insights into the fundamental mechanisms regulating the dynamics of the translation process. Visits to the group of Dr. Chiarugi, head of the Bioinformatics Unit of the Metabolic Research Laboratories of the Cambridge University (UK) are planned during the project.