Noncoding RNA Mechanisms involved in transcriptional and epigenetic plasticity of cancer cells
Background: Transcriptional reprogramming and cancer cell plasticity are emerging as a new hallmark of cancer, able to give cancer cells the ability to alter a specific aspect of their phenotype, either transiently or permanently, in response to challenging environments or harsh conditions. Regulatory non-coding RNAs, either short (microRNAs) and long (lncRNAs), are emerging as key elements in such regulatory mechanisms, providing a flexible, tunable and dynamic control of gene expression regulation [Kopp, 2018 Cell].
Aim: This project is aimed at investigating mechanisms provided by noncoding RNAs that are involved in the adaptive response and transcriptional reprogramming of breast cancer cells.
Activities: The candidate will focus on the high-resolution characterization of the function and the mechanism of one promising lncRNA candidate, which stood out as extremely relevant in modulating the tumour response to chemotherapy. In parallel, he/she will investigate the role of Target-induced-miRNA-degradation (TDMD) mechanism, a novel molecular mechanism in control of microRNA function [Ghini, 2018 Nat Comm], and its implication during reprogramming of breast cancer cells that occurs upon adaptation to chemotherapy, inter-conversion of Mammary Stem Cell (MaSC)-like to more differentiated cells, or epithelial-to-mesenchymal (EMT) transition.
Methodology: The project is highly interdisciplinary and involves experimental skills in different areas (molecular biology techniques, biochemical approaches, tissue culture in 2D, 3D and in vivo) with the use of cutting-edge approaches and state-of-the-art genomic technologies (i.e. RNAseq, ATACseq, Single-Cell sequencing, CRISPRi/a approaches, RAP, ChIRP, FISH…).