Foto del docente

Brunella Del Re

Assistant professor

Department of Pharmacy and Biotechnology

Academic discipline: BIO/18 Genetics


Keywords: mobile genetic elements retrotransposition LINE-1 biological effects of magnetic fied, radiofrequency, 5G epigenetics

1) Long Interspersed Nuclear elements (LINE) are transposable elements so abundant to represent large portions of the human genome (about 20%). They amplify themselves, inserting copies in new genomic locations, by a RNA-mediated retrotransposition process. Their mobility is generally repressed in most differentiated somatic cells, but it can be activated in several conditions. Until now the factors involved in LINE activation are still little known. Aim of this study is to gain understanding on how retrotransposition is regulated, using a L1 engineering element in an in vitro retrotransposition assay. 

2) Exposure to extremely low frequency magnetic fields (ELF-MF) is ubiquitous in industrialized countries. Until now, conclusive results on ELF-MF biological and health effects have not yet been obtained because of the high number of parameters that have to be considered. Aim of this study is to investigate on the biological effects, including genotoxicity, of ELF-MFs with different physical characteristics.

1) LINE elements belong to the non-LTR retrotransposon class and amplify themselves by a retrotransposition process consisting of several steps: L1 RNA transcription, transport to the cytoplasm, translation of its two ORFs, formation of ribonucleic particle, return to nucleus, reverse transcription and integration of retrotranscripts in a new genomic location by a molecular mechanism termed target-site primed reverse transcription (TPRT). Although the majority of human LINEs are defective, about 100 functional elements have been estimated. Their mobility can give arise to insertional mutagenesis, transduction, genomic deletions, thus modifying genome structure and function. This could on one hand contribute to genome evolution, on the other one cause a variety of diseases. Active in gem line cells, LINEs are generally repressed in most somatic cells. Until now, multiple factors that limit L1 retrotransposition at different molecular steps have been identified, including methylation, RNA interference, APOBEC3 proteins, L1 ribonucleoprotein sequestering in stress granules. Recently it has been observed, using an in vitro retrotransposition, that L1 retrotransposition can occur in some somatic cells, such as human embryonic, neuronal precursor, tumour cells; in addition several chemical and physical agents, including UV, heavy metals, benzo(a)pyrene, have been reported to induce retrotransposition. The cellular factors determining these LINE activations are still little known. The aim of the present research is to gain understanding on how retrotransposition is regulated, using a L1 engineering element in an in vitro retrotransposition assay. The study addresses two aspects. The first concerns L1 regulation in relationship with neural cell differentiation. A neuroblastoma cell line ha been chosen as a model because it is easily induced to differentiate in vitro towards neural phenotype. This cell line has been observed to be able to support L1 retrotransposition, though with a low frequency. Analysis will be performed in order to verify whether and how differentiation can influence L1 mobility, which cellular factors and which steps of retrotransposition process can be involved. The second aspect that will be addressed deals with those environmental factors able to influence L1 retrotransposition. The effect of several chemical and physical agents, including magnetic fields, temperature shocks, oxidants, will be investigated studying the signalling pathways involved.

2) Extremely low frequency magnetic fields (ELF-MF) can influence cell physiology so that they are used as therapeutic agents. However a clear picture is not yet emerging because of the high number of parameters that have to be considered. ELF-MF biological effects critically depend on exposure duration, signal characteristics, magnitude of magnetic induction, hence the results obtained by different laboratories are often not comparable. The aim of this study is to investigate the influence of ELF-MFs with different physical characterictics on some biological end points (proliferation index, viability, heat shock and differentiation marker expression) in several human cell types. In addition possible genotoxic effects will be evaluated assessing both single- and double-strand DNA break induction.

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