Ricerc@Sapienza

RNA-binding proteins (RBPs) play multiple roles in RNA metabolism and their mutation, delocalization and/or altered expression have been proposed to cause familial and sporadic amyotrophic latrla sclerosis (ALS). In our lab, human iPSC-derived motor neurons, skeletal muscle cells and neuromuscular organoids are used as in vitro model systems to study the role of the RBPs FUS, HuD/ELAVL4 and TDP-43 in ALS. To this aim, we have developed protocols for rapid and efficient conversion of human iPSCs into motor neurons and skeletal muscle cells. This method is based on the inducible expression of "programming factors" for the generation of spinal (NIL programming factors) or cranial (NIP programming factors) motor neurons, or skeletal muscle cells (Baf60c and MyoD) thanks to the integrative trasposable vector epiggyBac.

Pathogenic variants of the GNAO1 gene, encoding the alpha subunit of an inhibitory heterotrimeric guanine nucleotide-binding protein, have been linked to a neurodevelopmental disorder characterized by devlopmental delay, hypotonia, epilepsy and hyperkinetic movements. In our lab we use iPSCs to generate cortical neurons, brain organoids, rosette arrays, gastruloids and neuruloids to study the molecular mechanisms underlying this disorder, to test potential drugs and to develop new therapeutic approaches.