Objective
One knows today that an important part of the control of gene expression in eukaryotic cells occurs at the post-transcriptional level. Translation regulations tallow the cell to quickly responds to environmental changes by the recruitment of inactive mRNA molecules into active polysomes. This is specially true for ckines, growth factors and other regulatory proteins, the expression of which is transient and highly controlled. Furthermore, post-transcriptional regulation gene expression could be a major, and often unsuspected, cause of problems for efficient production of proteins of interest to the industry. Clearly, "Cell factories" discriminate between mRNAs for translation, leading to yield protein synthesis in some cases and very poor yields in others. Unfortunately we have currently only very limited information about the criteria of such distinctions.
This project involves eight laboratories, from six EU countries, each of them on a complementary aspect of translational control. Its purpose is to create efficient improvement of our understanding of translation regulation. Elaborating an European cooperation on translational control is essential for sex change; the national level of exchange is too weak, due to the small number on-working on gene translational regulation.
Our proposal constitutes a first and necessary step towards the creation of new v? and new cell lines capable of improved protein production both in terms of yield- specificity. The first step will be a "scientific walk" along the mRNA molecule laboratory studying a different part of the messenger, as well as the translating machinery. The mechanisms controlling mRNA expression at the translational lev involve interrelationships between the different aspects of the translation machine. The topics which will be considered are the following:
Analysis of the relationship between the translation efficiency and the ribosome of the cell. (CNR)
Inhibition of initiation factor elf-2 phosphorylation as a tool to enhance trans-efficiency (CSIC).
Internal ribosomes entry sites, a way to selectively translate messenger RNAs. (INSERM and UCAM.DBIOC)
Understanding mRNA-binding proteins as regulators of translational efficiency. Modulation of translation by the conditionally regulated polyadenylation of the Modulation of translation efficiency using artificial antisense. (UCAM, ULB, EMModulation of the mRNA stability. (ULB and UR1°
Our joint efforts will help us to elaborate firstly an information network, sec"translation tool box" aimed to be available to everybody and containing characcomponents of the translation regulation mechanisms.
A further step will result in the design, using this translational tool box, of generation of vectors containing translational regulatory signals. These signals allow a more efficient expression of the mRNA, or confer an inducible controlleit. The existence of inducible systems can be very useful in cases where the pis toxic to the cell or an environmental nuisance. Acting ath the translation of the advantage of having a very quick and reversible effect of inducers. This future of biotechnology to be of prime importance in the fast growing field of where extremely rigorous controls of gene expression in addition to those avail of transcription will be required.
The final step of the project will be
1) the characterization of these vectors in the reference CHO cells2) the characterization in CHO cells of translational regulators identified in laboratories. The reference molecule which will be used to test the expression the fibrolblast growth factor 2 that has already been produced using bicistronified from CHO cells in one of the laboratories.
Advances achieved through our cooperation will thus result in a more efficient,inducible translation of mRNAs. This will convert the basic "Cell Factories" into "ADAPTED Cell Factories".
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsRNA
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Topic(s)
Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
1640 Rhode-Saint-Genèse
Belgium