PTER team (January 2016)
THE TRANSLATION AND THE TRANSLATOME
Protein synthesis is a major step in the regulation of gene expression. More than 50% of the of the variation in protein levels is related to translational regulation (Schwanhäusser et al. 2011).
There is growing evidence that the translatome (defined as the fraction of all translated mRNAs, Figure 1) strongly correlates with the proteome and is and functionally relevant to cellular phenotypes (Wang et al. 2013).
The translatome is therefore an ideal framework for measuring gene expression to fill the gaps in gene regulation studies from genome to proteome, in the perspective of an integrated vision of cell physiology.
Figure 1: Gene expression, from genome to translatome (adapted from Keene et al, 2007)
- Characterize the pancreatic ß cells translatome under normal and pathological conditions, and identify the cellular role of a major regulator: Angel1.
We highlighted new translational regulations in the physiology of endocrine cells using pancreatic ß cells.
We have identified a new player, Angel1, which appears to play an important role in translation regulation of these cells.
Figure 2: Angel1 is a new regulator which is predominantly expressed in the pancreas and could regulate gene expression at two levels: size control of the poly (A) tail and translation.
The team PTER (Post Transcriptional and Epigenetic Regulations) studies translational regulation in gene expression control in normal and pathological cells.
Our goal is to build a new picture of gene expression representative of cell dynamics, focusing on translational regulation as a source of a wide range of epigenetic changes as revealed recently by ribosome profiling.
This vision of cell physiology leads us to identify important regulators of metabolic changes in normal and pathological situations. They represent potential therapeutic targets from which, when possible, lead compounds can be proposed for the design of therapeutic agents.
- Translational Research Project : Development of a cell death-inducing peptide.
We characterized the pro-necrotic properties of an Angel1-derived peptide in several cancer cell lines (Masse et al., 2014).
We are developping antitumor approaches in collaboration with several teams working on cell targeting strategies.
Figure 3: The A1 peptide induces rapid cell death involving a dramatic disorganization of the F-actin network, cell blebbing and membrane permeabilization
Our research programs needs lead us to develop different techniques to study the translatome, adapting molecular biology protocols to optimize the bioinformatic analysis. Only recently we gained access to the translatome at a genome-wide level. Beyond the acquisition of data, comprehensive exploration of the results need bioinformatic developments. The biological knowledge that they produce will be further integrated in wider regulatory networks to establish a comprehensive representation of the regulation of gene expression and a real continuum from the genome to the proteome” in an integrative computational biology framework.
- Identify new modes of epigenetic regulation of gene expression: particularly with Angel1 studies in the pancreatic beta cell, as well as during lymphocyte transformation during parasitic infection.
- Complete our expertise in translatome studies to achieve a wholy integrative bridging biology and bioinformatics.
- Fill the gaps in gene regulation studies from genome to proteome to open new thematic areas for the integration of “omics” data in a complete computational biology framework