Objectif Regulation of gene expression is a fundamental process in all cellular systems. While the major steps in gene regulation such as transcription and translation are well understood, the role of tRNA availability (e.g. abundance, half-life) in regulating translation is largely unknown. The ultimate objective of this proposal is to investigate how tRNA availability within a cell can influence which mRNA molecules are actively translated by the ribosome. More specifically, it aims to address (i) whether mechanisms such as transcription, nucleo-cytoplasmic transport and degradation vary for individual tRNAs coding for different amino acids and (ii) how altered tRNA dynamics can affect protein abundance, and hence fitness, in different cellular conditions.To address these questions, I propose systematically charting the tRNA abundance landscape using yeast as a model organism. I will quantitatively investigate the processes of tRNA production, transport and degradation, in order to determine which steps in tRNA homeostasis are altered under diverse stress conditions, compared to optimal growth conditions. I will then investigate the impact of tRNA dynamics in cell fitness through competitive growth experiments. In this manner, I propose to construct the first dynamic map of tRNA abundance, which holds the potential to help understand the process of gene expression regulation in fine detail.In the long-term, the goals described in this proposal will not only provide new insights into regulatory mechanisms of protein translation but will also help to achieve a better understanding of factors that influence fitness and cell survival. With recent discoveries relating changes in tRNA abundance to apoptosis and gene misregulation in tumorigenic cells, future research on understanding how tRNA availability is regulated and how it contributes to cell survival could lead to new strategies for the rational design of molecular therapies against cancer. Champ scientifique natural sciencesearth and related environmental sciencesphysical geographycartographynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural scienceschemical sciencesorganic chemistryaminesmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Appel à propositions FP7-PEOPLE-2012-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur MEDICAL RESEARCH COUNCIL Contribution de l’UE € 221 606,40 Adresse 20 Park Crescent W1B 1AL LONDON Royaume-Uni Voir sur la carte Type d’activité Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contact administratif Samantha Skehel (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée