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 2020, 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, and we identified several features regulating ribosome elongation. In this PhD project, we now aim to take these findings further in the context of cancer cells or under conditions of environmental perturbations, in cases where misregulation of translation is thought to play a major role, notably in hepatocellular carcinoma. This highly interdisciplinary project combines wet lab experiments (multi-omics) and computational work dry (bioinformatics, data modeling), and leverages 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, PNAS 2020, http://www.pnas.org/lookup/doi/10.1073/pnas.1918145117
For any information on available current or future positions, please contact [email protected]