Num. Contratto:
IRSN LW 2024-0012

Coordinatore: ENEA (Italia)

Responsabile ENEA: PAZZAGLIA SIMONETTA - SSPT-BIOTEC-RED (CASACCIA)

Ruolo ENEA: COORD

Sito Web: https://pianoforte-partnership.eu/discover/

Programma Quadro: HORIZON EUROPE

Programma UE: Euratom radioprotezione - Radioprotezione

Area Tematica: Radioprotection

Tipo Progetto: Programme Cofund Actions

Descrizione:

Radiation carcinogenesis has classically been attributed to unrepaired or misrepaired DNA damage. By now, there is increasing recognition that radiation can induce changes within the microenvironment and cause epigenetic modifications, which can also contribute to the development of cancer, challenging the conventional target theory in radiobiology. However, the interplay between DNA damage, microenvironmental changes, and epigenetic modifications in radiation-induced carcinogenesis is complex and not yet fully understood. DISCOVER will study the impact of radiation-induced changes in the microenvironment and the influence of related cell communication processes on carcinogenesis. The project will exploit a robust model of radiation-induced carcinogenesis, the Ptch1+/- mice, exhibiting a genetic predisposition for development of medulloblastoma (MB), a cerebellar tumour. Irradiation of these mice, even at low dose, increases MB incidence. The project aims to understand how different cerebellar populations, such as granule cell precursors, the MB cell of origin, and astrocytes, microglia and endothelium, representing microenvironmental components, respond to moderate (2 Gy) and low (0.1 Gy) radiation doses and contribute to tumour formation. Model systems of different complexity including (i) Ptch1+/- mice, (ii) ex-vivo cerebellum slices and (iii) in vitro cerebellar cell cultures, will be used to evaluate the effect of the microenvironment in transmitting radiation signals driving carcinogenesis. We will conduct a comprehensive analysis of various types of data, including morphology, function, tumourigenesis and omics data. We will also investigate secretome, as well as extracellular vesicles from exposed tissue and their specific bioactive cargo for their role in mediating radiation tumourigenesis. An integrated analysis of DISCOVER animal data and publicly available human brain cancer data aims to identify patterns/signatures for MB development. By adopting this comprehensive approach, DISCOVER aims to uncover the interactions between different cellular components of the cerebellar microenvironment and their role in radiation oncogenesis. Overall, these findings have the potential to improve our mechanistic understanding of the pathogenesis of radiation-induced cancer with important implications for human health risk assessment.

Attività svolta da ENEA:

L'ENEA coordina il progetto ed è leader del WP6 “Project Management” ed il WP7 “Training, Dissemination and Exploitation”, in stretta collaborazione con gli altri partner del progetto Il progetto prevede per ENEA l’esecuzione di esperimenti (in vitro, ex vivoe in vivo) per l’identificazione di segnali di danno e dei meccanismi molecolari che le cellule del microambiente potrebbero trasferire sulla cellula target, responsabile dell’insorgenza tumorale.

Note:

1 Rif. Progetto PIANOFORTE Id 101061037

Posizione:
1773

Codice Atto:
PS5ABH

Atto di approvazione ENEA:
23/2024/SSPT-TECS

Unità alla stipula:
SSPT-TECS-TEB

Costo eleggibile del Progetto: 1.344.970,00

Contributo al Progetto: 847.331,00

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Costo eleggibile per ENEA: 749.970,00

Contributo ad ENEA: 472.481,00

Anno di stipula:
2024

Durata in mesi:
36

Data di inizio:
01-02-2024

Data di scadenza:
31-01-2027