In vitro modelling of ALS pathology

Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) are caused by the death of nerve cells. Within these dying cells, clumps- termed aggregates - of proteins are present, and can cause cell death. Cellular assemblies of liquid nature of the given proteins have been found to be the precursors of these deposits. While these assemblies have been (and still are being) studied in detail, information pertaining to the aggregation phenomenon is lacking. Many regard these deposits as ordered fiber-like structures, similar to what has been described in Alzheimer’s disease. We, however, hypothesize that these aggregates are of less-ordered, random - amorphous - nature. While these deposits contain many protein components, to reduce the complexity of our model, we only chose one of them. This component was produced in bacteria and purified. We found this protein to form liquid assemblies in the test- tube, which then turn later to solid aggregates. Indeed, we saw that this aggregate did not have a fiber like, rather amorphous, structure. During the PhD, we want to further dissect this model, and gather mechanistic information about the liquid-like assembly, the solid aggregate and the process of their formation. We aim to extend this model by including different bio-molecules. Eventually we will validate the model in cells.