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

Descripción del proyecto

Vías de regulación del lisosoma

Los lisosomas son orgánulos celulares que contienen enzimas hidrolíticas y participan en procesos fisiológicos clave de las células. Se sabe que la disfunción lisosómica está implicada en la aparición de un amplio conjunto de enfermedades humanas. Es importante destacar que la mayoría de las funciones realizadas por los lisosomas dependen de actividades hidrolíticas dentro de su luz. No obstante, la regulación de las actividades de los lisosomas y su papel en el gobierno del destino celular siguen planteando cuestiones cruciales. Por lo tanto, un conocimiento más detallado de las rutas de señalización que rigen la regulación de los lisosomas podría proporcionar nuevas herramientas terapéuticas para tratar estas enfermedades. El equipo del proyecto CytoLysoReg, financiado con fondos europeos, investigará las propiedades moleculares y biofísicas que permiten a las citocinas regular los lisosomas. El objetivo es permitir a los científicos manipular los lisosomas como método de tratamiento de enfermedades relacionadas con los lisosomas.

Objetivo

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.

Coordinador

UNIVERSIDAD DE SEVILLA
Aportación neta de la UEn
€ 172 932,48
Dirección
CALLE S. FERNANDO 4
41004 Sevilla
España

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Región
Sur Andalucía Sevilla
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 172 932,48