Doctoral Candidates

Bakcground: I am a 24 years old graduate in Genetics and Molecular Biology at Sapienza University in Rome. For my master thesis I worked on characterizing lncRNAs in both physiological and pathological muscular contexts. There my research spanned from identifying RNA in human systems to then functionally characterizing their mechanisms of action in iPSC-derived cardiomyocytes. I always had a high degree of attraction to developmental biology, given its multifaceted nature and various systems to inquire on it. Both the zebrafish and the organoids model, represent tools I will be delighted to explore thoroughly. I am thrilled by the opportunity to put my effort into an advanced research complemented with direct approaches, including possible future therapeutic applications and regenerative medicine.

Research Project: The investigation will delve into how the mechanical state of zebrafish eye organoids translates into changes in epigenetic patterning and find which matrix compositions better support the in vivo epigenetic state. The objectives are to first modify the tensional forces of eye organoids by: 1) modification of YAP signalling, and 2) the use of ferrofluidic droplets to alter the mechanical integrity of the tissue. The changes in epigenetic signatures in response to these perturbations will be analysed by RNA-seq, ATAC-seq and WGBS to identify specific gene regulatory regions of the chromatin that adapt to changes in those cell-extrinsic mechanical inputs. The aim of the PhD student will be to use these mechanically sensitive gene regulatory regions to explore which matrices or alternative synthetic hydrogels mimic better the in vivo gene-regulatory state. This approach will permit for the efficient selection of settings that support optimal organoid morphogenesis.

Expected results: We will develop a highly innovative approach to rank successful organoid formation from an unprecedented epigenetic angle, aimed at reproducing the in vivo epigenetic context, and its crosstalk with the surrounding environment. This information will be used to determine the optimal external substrate which will mimic in vivo epigenetic patterning in an in vitro context. The experiments will set the foundations for understanding how changes in the mechanical state of the organoid and of their extracellular environment impact on gene-regulatory mechanisms in 3D cell structures.