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TRANSLATE Report Summary

Project ID: 338999
Funded under: FP7-IDEAS-ERC
Country: Italy

Mid-Term Report Summary - TRANSLATE (Noncoding and Translational Modulation of Gene Expression and Epigenetic Changes)

The human immune system is necessary for fighting infections. In addition, it is abnormally activated in autoimmune diseases, and is repressed in cancer patients. In order to devise better therapeutical strategies, we need to know the mechanisms that regulate the function of the human immune system. In the recent years, the capability to sequence DNA at low cost and at high efficiency, coupled with the possibility to purify from human blood cellular subsets, has led to an explosion in the knowledge of the genes that regulate immune function. In particular, by focusing on subsets of T lymphocytes, we have been able to construct expression maps that helped us to identify diagnostic biomarkers and therapeutic targets. From there, we hope to build new therapies.
An existing bias is that we have so far studied the “transcriptome” (the genes expressed at the mRNA level) assuming that the “translatome” (the genes translated from mRNA to protein) faithfully reflected the transcriptome. This is not the case, because many mRNAs are silenced at the “translatome” level. For this reason, we have started a project aimed at defining gene expression maps that take in account the transition from the transcriptome to the translatome. Through the combination of ribosome profiling and experimental validation, we have been able to construct new gene expression maps that better describe the metabolism and function of T lymphocytes. These maps are a knowledge endpoint that can be exploited for a more focused and efficient definition of biomarkers and therapeutic targets, expecially in conditions where the “transcriptome” fails to be predictive or to generate targets.

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