Amiotrophic Lateral Sclerosis (ALS) is one of the most devastating degenerative neuromuscular disorders, characterized by motoneuron (MN) progressive degeneration, muscle atrophy and fatal paralysis.
Even though biomedical research in the field witnessed major efforts profused in the last years, many facets of ALS etiopathology remains elusive, concerning in particular the mechanism through which physiological functions are corrupted in diseased conditions.
The A1 project aims at applying state-of-the-art nanotechnologies as tools to elucidate the molecular, cellular and tissutal processes underlying nervous system differentiation and homeostasis, as a prerequisite to understand their pathological mis-regulation in the occurring neuromuscular degeneration.
Mouse motoneuron unit
Among the numerous genes involved in ALS onset and progression, the unit is focusing on the pleiotropic RNA-binding protein FUS/TLS (FUS), whose mutations have been found in 4% of familial cases of ALS. We are taking advantage of mouse Embryonic Stem Cells (mESCs) as a powerful model where investigating the role of FUS in ALS molecular etiopathogenesis.
Human iPSCs Unit
Induced Pluripotent Stem Cells (iPSCs) provide an opportunity to study human diseases in those cases where appropriate models are not available. We have derived human ALS-iPSCs that can generate motoneurons or muscle cells in vitro. This cell system recapitulates key hallmarks of the pathology, such as aberrant localization of mutated proteins in response to cellular stress, and can be exploited to investigate the correlation between mutations and ALS ethiopathogenesis.
Mouse skeletal muscle unit
The muscle unit is focused on the histological, molecular, functional and biomechanical analysis on both skeletal muscle and nervous tissue of the ALS animal models.
Electrophysiology unit
The unit develops electrphysiological and time-lapse imaging recording of neuronal and microglial cells activity to characterize their interactions in physiological and pathological conditions (ALS and brain tumours).
Biochemistry unit
The unit is specialized in protein engineering by genetic and chemical modification methods. In particular, transport protein variants are designed, cloned, expressed and purified. Protein carriers are thus exploited for delivery of pharma products, diagnostic probes and nucleic acids to cells and tissues.