Phd in HUMAN BIOLOGY AND MEDICAL GENETICS

Research: The mutual modulation of DNA methylation and microRNAs and its impact on physiological and pathological conditions

Recent studies highlight a relevant cross-talk and mutual regulation between DNA methylation and miRNAs, adding a layer of complexity to the epigenetic regulation of disease-associated processes. In this frameshift, my Ph.D. project will be centered on the study of the relationship between DNA methylation and miRNAs synthesis, both in physiological and pathological conditions. First, at the basic level, my aim is to investigate how the alteration of the one-carbon metabolism (deprivation of B-vitamins, administration of S-adenosylmethionine, Deazaaristeromycin and 3-Deazaadenosine) can influence the mutual modulation of the two epigenetic traits. Second, is to verify the possibility of these metabolic alterations and of this mutual epigenetic modulation to affect pathogenic processes, specially the gene expression alteration in Cystic Fibrosis (CF) and the neuroinflammatory processes associated with neurodegenerative diseases (particularly Alzheimer’s Disease, AD). For the first year, in the context of CF, the objective is to study the methylation status of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) and Foxi1 (Forkhead Box I1) in nasal airway epithelial stem-induced cells and organoids from CF patients and verify if hypomethylation conditions can result in an increase of CFTR expression. On the other hand, in the context of AD, the aim is to verify if DNA methylation modulates PICALM (Phosphatidylinositol Binding Clathrin Assembly Protein) and LRP1 (LDL Receptor Related Protein 1) expression and if one-carbon metabolism modulation can improve amyloid scavenging, in neuroblastoma cells and in blood-brain-barrier models.