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Cellular and Biophysical Approach to Understand the Cytokine-mediated Regulation of the Lysosomal Hydrolytic Capacity

Project description

Pathways for lysosome regulation

Lysosomes, cell organelles containing hydrolytic enzymes, participate in key physiological processes of cells. Lysosome dysfunction is known to be involved at the onset of an ample set of human diseases. Importantly, most of the functions carried out by lysosomes depend on hydrolytic activities within their lumen. Nonetheless, the regulation of lysosome activities and their role in cell fate governance still raise crucial questions. Therefore, a deeper understanding of the signalling pathways governing the regulation of lysosomes could provide new therapeutic tools to treat these diseases. The EU-funded CytoLysoReg project will investigate the molecular and biophysical properties that enable cytokines to regulate lysosomes. The goal is to allow scientists to manipulate lysosomes as an approach to treat lysosomal-related diseases.

Objective

Dysfunction of lysosomes—the recycling plants of cells, now recognised to participate in multiple aspects of cell physiology—is involved at the onset of several human diseases. Importantly, most of the functions carried out by lysosomes depend on hydrolytic activities within their lumen. Thus, a deeper understanding of the signalling pathways involved in the regulation of lysosomes would provide new tools to ameliorate the symptoms associated with these diseases. The regulation of lysosomal gene expression was partially elucidated by the discovery of the role played by the mTOR-TFEB axis during starvation. However, as recently shown by the researcher (Nature Comm 2018) and others the cytokines-STAT3 axis also contributes to lysosomal regulation. However, the molecular mechanisms of the cytokine-mediated lysosomal regulation still remain unresolved. Thus, the herein proposed project (CytoLysoReg) is aimed at unveiling the molecular and biophysical properties allowing cytokines to regulate lysosomes. CytoLysoReg is an innovative, multidisciplinary project based on international collaborations and preliminary data generated by the researcher during his work as Senior Research Associate at the University of Dundee. The data generated during the execution of CytoLysoReg on lysosomal regulation will allow us to manipulate lysosomes as an approach to treat lysosomal-related diseases (e.g. cancer, LSDs). The role of Prof. Diaz-Quintana as supervisor will be essential, providing his expertise in biophysics and protein structure, and facilitating the integration of the researcher into the host institution (IIQ-Seville). Finally, after finishing the MSCA-IF fellowship, the researcher will be invited to develop his independent scientific career and reinforce the Biological Chemistry line—considered a strategic research line to be developed at the host institute—at the IIQ-Seville thanks to the ongoing MSCA Fellows Stabilisation and Recruitment of Talent Programme of the US.

Coordinator

UNIVERSIDAD DE SEVILLA
Net EU contribution
€ 172 932,48
Address
CALLE S. FERNANDO 4
41004 Sevilla
Spain

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Region
Sur Andalucía Sevilla
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 172 932,48