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

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.