Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, characterized by progressive motor neurons (MNs) degeneration, which leads to a deterioration of neuromuscular functions, causing weakness, paralysis and atrophy of skeletal muscles.
ALS is a disease of obscure aetiology, for which neither a cure nor a therapeutic option is available.
Some genetic variants have been associated to the familial forms of the disease, including mutations in C9orf72, SOD1, TARDBP and FUS. However, most of ALS cases are sporadic and believed to be caused by the effect of environmental factors such as exposure to virus, fertilizers, heavy metals, dietary and others.
Given the strong influence that environmental factors play in modulating the epigenome of a cell, the goal of this project is to understand the epigenetic changes and associated gene expression profile that precede the symptom of ALS in order to identify crucial signatures that can anticipate the disease onset. For this purpose, we will perform chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) and transcriptome analysis (RNA-Seq) of pre-symptomatic SOD1G93A tissue.
The match between ChIP-Seq and RNA-Seq could led to better understand the development of this devastating disease and design new therapeutic strategies.
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, characterized by a progressive loss of the motor neurons at the spinal or bulbar level. Unfortunately, so far, there are no explicit evidences of the final causative mechanisms and despite ALS is being clinically described in 1874 the pathogenesis mechanisms have not yet been fully understood.
One of the current limitations in ALS battle is the impossibility to be diagnosed before ALS becomes clinically evident.
The novelty of this project is the epigenetic approach to deeply investigate the chromatin landscape of both spinal cord and skeletal muscle at a pre-symptomatic stage of the disease. The achievement of these objectives will be extremely powerful to understand the molecular mechanisms triggering this devastating disease. Using innovative approaches, such as ChIP-seq and RNA-seq strategy, we will map the epigenetic and transcriptional changes that will occur in both in spinal cord and muscle compartment. Moreover, this project will increase the knowledge about the role of these two different tissues in the ALS progression.
Using a genome-wide approach we will unbiased describe the epigenetic and transcriptional changes leading to the neuron degeneration and muscle atrophy providing fruitful information for the discover of new diagnostic biomarkers for ALS.