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

Projektbeschreibung

Wege zur Regulierung von Lysosomen

Lysosomen – Zellorganellen, die hydrolytische Enzyme enthalten – sind an wichtigen physiologischen Zellprozessen beteiligt. Es ist bekannt, dass eine Dysfunktion der Lysosomen an der Entstehung zahlreicher menschlicher Erkrankungen beteiligt ist. Die meisten der von Lysosomen ausgeführten Funktionen hängen von hydrolytischen Aktivitäten in ihrem Lumen ab. Dennoch werfen die Regulierung der Lysosomen-Aktivitäten und ihre Rolle bei der Steuerung des Zellschicksals noch immer entscheidende Fragen auf. Ein eingehenderes Verständnis der Signalwege, die die Regulierung der Lysosomen steuern, könnte daher neue therapeutische Instrumente zur Behandlung dieser Erkrankungen liefern. Das EU-finanzierte Projekt CytoLysoReg wird die molekularen und biophysikalischen Eigenschaften untersuchen, die es Zytokinen erlauben, Lysosomen zu regulieren. Ziel ist es, der Wissenschaft die Möglichkeit zu bieten, Lysosomen zu manipulieren, um lysosomal bedingte Erkrankungen zu behandeln.

Ziel

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.

Koordinator

UNIVERSIDAD DE SEVILLA
Netto-EU-Beitrag
€ 172 932,48
Adresse
CALLE S. FERNANDO 4
41004 Sevilla
Spanien

Auf der Karte ansehen

Region
Sur Andalucía Sevilla
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
€ 172 932,48