Cel Translation of the genetic code into functional proteins is a fundamental biological process essential for cell survival and function. tRNAs are critical in this process because they recognize the codons on the messenger RNA and bring the cognate amino acid to the nascent peptide. To become functional, tRNAs undergo a series of processing steps and chemical modifications. Recently, my host group discovered that cells lacking wobble uridine modifications in the tRNA anticodon display translational slow down, a defect that triggers widespread protein aggregation in yeast and nematodes. These findings were the first to link tRNA metabolism to protein quality control and established tRNA metabolism as a novel layer in the regulation of protein homeostasis. However, the mechanisms underlying this phenomenon remain unknown.My goal is to elucidate how tRNA processing and modifications regulate protein quality control, by integrating genetic, biochemical, transcriptomic, translatomic and proteomic approaches.- First, I will identify tRNA biosynthesis genes that are critical for protein aggregation, by assessing global protein homeostasis in yeast cells lacking genes required for tRNA processing and modifications. - Second, I will characterize transcriptome-wide translation by ribosome profiling to determine whether protein aggregation phenotypes are accompanied by translational defect. This will reveal which tRNA processing and modifications are essential for optimal co-translational protein folding. - Finally, I will use yeast and nematode models of neurodegenerative diseases to test the functional importance of candidate steps of tRNA metabolism in disease-associated protein aggregation.My project will comprehensively address the link between tRNA metabolism and protein homeostasis. In particular, it will bridge RNA and protein quality control pathways and shed mechanistic insights into neurodegenerative diseases that originate from tRNA dysfunction. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingnatural sciencesbiological sciencesgeneticsRNAnatural scienceschemical sciencesorganic chemistryaminesmedical and health sciencesbasic medicinephysiologyhomeostasis Program(-y) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Temat(-y) MSCA-IF-2016 - Individual Fellowships Zaproszenie do składania wniosków H2020-MSCA-IF-2016 Zobacz inne projekty w ramach tego zaproszenia System finansowania MSCA-IF-EF-ST - Standard EF Koordynator UNIVERSITAET BERN Wkład UE netto € 112 951,40 Adres HOCHSCHULSTRASSE 6 3012 Bern Szwajcaria Zobacz na mapie Region Schweiz/Suisse/Svizzera Espace Mittelland Bern / Berne Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 124 255,55 Uczestnicy (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Zakończenie uczestnictwa Niemcy Wkład UE netto € 46 509,40 Adres HOFGARTENSTRASSE 8 80539 Munchen Zobacz na mapie Region Bayern Oberbayern München, Kreisfreie Stadt Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 46 509,40