Translational defects in motor neuron diseases

The growing interest of the scientific community for post-transcriptional control of gene expression is moving towards a completely new concept of the protein synthesis machinery, i.e. polyribosome. Polyribosomes are now recognized as platforms where several post-transcriptional and translational controls, from RNA binding proteins to non-coding RNA, are impinging to shape cell proteomes. Despite this interest, the overall picture is still sketchy at best. In this context, our laboratory studies the super-structural organization and function of the polyribosome in vitro and in vivo and applies our discoveries to shed light into neuro-generative diseases of motor neurons and bacterial infections. In particular we are interested in better understanding global and local translational defects in Muscular Spinal Atrophy (in collaboration with the University of Edinburgh and the NICO of Turin) and Amyotrophic Lateral Sclerosis (in collaboration with the Cibio di Trento, the San Raffaele Life and Health University in Milan, the University College London). The experimental methods we use range from classical biochemical and biophysical techniques to the latest sequencing approaches for positional analysis of ribosomes at single nucleotide resolution (Ribo-Seq). These studies are applied to a number of organisms (bacteria, yeast, mouse, human and other non-model organisms) and are accompanied by analysis of polyribosomes by high-resolution imaging (super-resolved microscopy in collaboration with IIT Genova, Atomic Force microscopy in collaboration with FBK Trento, cryo-EM in collaboration with IBF Milano). The integration of omics and structural aspects requires specific analytical and computational techniques, which we develop (in collaboration with DISI University of Trento and the University of Edinburgh) and use to deepen our understanding of these devastating diseases. As biological systems we deploy our experience in the preparation of primary neuronal cultures in microfluidic chambers and murine tissues obtained from various disease models. These in vivo systems are finally integrated with in vitro approaches for the molecular characterization of the processes under study.

Members:
Lorenzo Lunelli
Mario Milani
Gurav Sharma
Gabriella Viero (Principal investigator)