Ricerc@Sapienza

Using Drosophila melanogaster as model organism, which is considered a valuable model for the analysis of the biological consequences of radiation exposure, we have recently found that a pre-exposure to a dose of 40 cGy at dose rate of about 2.5 mGy/h (Low Dose Low Dose Rate (LDLDR)) confers radioresistance to chromosomal DNA damage after a challenging exposure of 10Gy. This revealed us that a radio-adaptive response also exists for Drosophila mitotic cells after a LDLDR treatment. In addition, our preliminary genetic and RNA seq data indicated that this response is mediated by DNA damage response pathway and strongly depends on modulations of lincRNAs and transcripts involved in ribosome biogenesis. Furthermore, we have also found that the permanence on a strongly reduced radiation environment, such as the INFN-LNGS underground laboratory can indeed affect Drosophila development and, depending on the genetic profile, may affect viability for several generations even when flies are moved back to the reference radiation environment. Collectively, our findings suggest that small variations of radiation dose/dose rate above and below background, can trigger significant biological responses on a complex multicellular organism and reinforce the view that the Linear No Threshold (LNT) model cannot be generally taken into account for the evaluation of radiation risks. My proposal aims at investigating the biological effects of LDLDR on Drosophila cells by tackling two main tasks: (TASK 1) Characterizing the LDLDR-induced resistance to dsDNA breaks; (TASK 2) Validating the RNA seq data in Drosophila to understand the molecular bases underlying the LDLDR-induced radio-adaptive response.