Descrizione del progetto
Percorsi per la regolazione dei lisosomi
I lisosomi, ovvero organuli cellulari contenenti enzimi idrolitici, sono coinvolti in processi fisiologici cardine delle cellule. La disfunzione dei lisosomi è nota manifestarsi all’insorgenza di un’ampia serie di malattie umane. L’aspetto più importante è che la maggior parte delle funzioni svolte dai lisosomi dipendono dalle attività idrolitiche all’interno del loro lume. Ciononostante, la regolazione delle attività dei lisosomi e del loro ruolo nella gestione del destino cellulare sollevano tuttora interrogativi fondamentali. Pertanto, una migliore comprensione delle vie di segnalazione che disciplinano la regolazione dei lisosomi potrebbe fornire nuovi strumenti terapeutici per il trattamento di tali malattie. Il progetto CytoLysoReg, finanziato dall’UE, studierà le proprietà molecolari e biofisiche che permettono alle citochine di regolare i lisosomi. L’obiettivo consiste nel permettere agli scienziati la manipolazione dei lisosomi come approccio per il trattamento delle malattie legate ai lisosomi.
Obiettivo
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.
Campo scientifico
- engineering and technologyenvironmental engineeringwaste managementwaste treatment processesrecycling
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinephysiology
- natural sciencesbiological sciencesbiophysics
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
41004 Sevilla
Spagna