REBuILD · Exploring the role of TFEB in exosome biology and in novel approaches for treatment of lysosomal diseases
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-01-01 → 2018-01-31
- EU contribution
- €180,277
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Exploring the role of TFEB in exosome biology and in novel approaches for treatment of lysosomal diseases
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.
Data: CORDIS, © European Union
Project objective
Exosomes are small vesicles released to the extracellular environment by almost every cell type, with important functions in mediating intercellular communication in several physiological processes, including organism development, immune responses, neuronal communication and tissue repair. In addition, these vesicles have attracted much interest from the biomedical research community for their potential as biomarkers for diseases, therapeutic agents and vehicles for drug delivery. Despite this, little is known about the mechanism and molecular players involved in exosome biogenesis and secretion. The aim of this application is to expand our current knowledge on exosome biology and their therapeutic potential. Preliminary results suggest that Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, lysosomal exocytosis and autophagy induction, also controls the expression of various exosome-associated genes. By using mouse and human cells upregulated or knocked-down for TFEB expression, the applicant will establish a role for TFEB in exosome biogenesis, cargo selectivity and secretion. Furthermore, the applicant will determine the role of other TFEB-related cellular pathways, including starvation and Ca2+-related pathways, in regulating exosome formation. Finally, the applicant will explore the therapeutic potential of exosomes in cellular and mouse models of lysosomal storage disorders (LSDs). Collectively, this application combines both basic research and translational approaches to expand our current understanding of exosome biology and to provide proof of principle for novel therapeutic approaches of rare diseases.
Original text from CORDIS.
Participants
- FONDAZIONE TELETHON ETS · ROMACoordinatorItaly
Links
Data: CORDIS, © European Union