Analysis of Gene and microRNA Function through High-Content Screening
Conference Recording Jul 28, 2014
About the Speaker
Dr. Mano received his PhD in Biochemistry from the University of Coimbra, Portugal, where he became an expert in non-viral methods for gene delivery and he subsequently worked as a Post-Doctoral fellow at the Laboratory of Molecular Medicine at ICGEB Trieste, focusing his research activity on the understanding of the cellular and molecular mechanisms governing cell transduction by gene transfer vectors based on the adeno-associated virus. Starting from September 2008, Dr. Mano has taken the position of Scientific Manager of the High-Throughput Screening Facility at the ICGEB Trieste. Dr. Mano was responsible for the initial setting-up of this screening Facility and, since then he has been responsible for coordinating the different screening projects with intra- and extra-mural investigators and supervising all the activities performed in the Facility. Research activity of Dr. Mano is focused on high-throughput and high-content screening using genome-wide siRNA and microRNA libraries.Abstract
Phenotypic high-content screening enables the systematic testing of a large number of reagents, such as genome-wide libraries of siRNAs and microRNAs, allowing the unbiased analysis of a high number of cells, at the single-cell level. This presentation will discuss successful examples of the use of high-content screening to characterize gene and microRNA function.As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. To explore the potential of microRNAs in inducing cardiac regeneration, we performed a high-content screening aimed at identifying microRNAs able to increase proliferation of cardiac myocytes. Using this approach, we identified a restricted number of microRNAs able to very efficiently increase the proliferation of both neonatal and adult cardiomyocytes in vitro and in vivo. In a mouse model of myocardial infarction, these microRNAs stimulated marked cardiac regeneration and a complete recovery of cardiac functional parameters.Other screenings will be discussed, including the identification of microRNAs counteracting cellular senescence and of host cell factors and microRNAs involved in restricting cell transduction by gene therapy vectors based on the Adeno-Associated virus.