This project builds on our longstanding interest to understand gene regulatory mechanisms in the liver, and notably the links between circadian rhythms, feeding/fasting cycles and liver physiology. In that context, we recently focused on protein translation and protein accumulation levels in whole liver extracts and in cell nuclei. Recently (see Gobet 2019, below) we generated and modeled ribosome profiling (RP) data and uncovered codon-specific and inter-site dwell times (DTs) determining ribosome elongation rate in mammals. These DTs were highly stable across all conditions tested. In parallel, we quantified (aminoacyl-) tRNA levels in mouse liver and identified several features regulating ribosome elongation, such as aminoacylation levels and tRNA/codon usage balance. In this PhD project, we now aim to take these findings further in the context of cancer cells, in cases were misregulation of translation is thought to play a major role, such as hepatocellular carcinoma. This highly interdisciplinary project combines wet lab experiments (multi-omics) and dry (bioinformatics, data modeling) combining concepts & tools from molecular biology, gene regulation, bioinformatics.
Links to representative recent publications form our lab, illustrating the questions and methodologies:
- Mauvoisin, PNAS 2014, https://www.pnas.org/content/111/1/167
- Wang, Cell Metabolism 2017, https://www.sciencedirect.com/science/article/pii/S1550413116305344
- Gobet, Curr Opin Genet Dev 2017, https://www.sciencedirect.com/science/article/pii/S0959437X1730031X
- Gobet, bioRxiv 2019, https://www.biorxiv.org/content/10.1101/551838v1
For any information on available current or future positions, please contact [email protected]