Exploring the role of TFEB in exosome biology and in novel approaches for treatment of lysosomal diseases

Project Information

REBuILD

Grant agreement ID: 661271

DOI

10.3030/661271

Project closed

EC signature date 4 May 2015

Start date 1 January 2016

End date 31 January 2018

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 180 277,20

EU contribution

€ 180 277,20

Coordinated by

FONDAZIONE TELETHON ETS
Italy

Periodic Reporting for period 1 - REBuILD (Exploring the role of TFEB in exosome biology and in novel approaches for treatment of lysosomal diseases)

Reporting period: 2016-01-01 to 2017-12-31

Summary of the context and overall objectives of the project

Cell-to-cell communication is a fundamental biological mechanism that allows the adaptation of any organism to environmental changes. Cells sense and respond to environmental cues, such as nutrient availability and stress, via the activation of important signaling molecules, whose activity is crucial to ensure the correct biological responses to constantly changing external demands. Importantly, these mechanisms are often de-regulated in several human diseases, ranging from metabolic disorders to cancer. Despite their relevance, the mechanisms by which cells sense and signal environmental and nutritional inputs is poorly understood. The main goal of this project is to get a deeper molecular understanding on these processes and on their relevance to disease.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Cell-to-cell communication represents an essential process for the coordination of cell functions and the environmental adaptation of multicellular organisms. Primary mediators of such communication are represented by small cellular vesicles released by most cell types known as exosomes.
This project has extended our knowledge on the molecular mechanisms controlling exosome biogenesis and secretion. Furthermore, this project has provided new important data identifying the mechanism by which cells sense and signal nutrient availability in physiological and pathological conditions.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

De-regulation of the mechanisms responsible for nutrient sensing and cell-to-cell communication has been associated to multiple human diseases, including metabolic disorders and cancer. The data generated in this project have profoundly advanced our understanding on the cellular events that modulate such processes. This will have a major impact on both basic and translational science, as it identifies key therapeutic targets for metabolic disease conditions.

TFEB at a glance