The Poly-STOP project received a 2020 BIST Ignite Grant in June 2021.
The expansion of certain amino acid chains (polyglutamines, PolyQ) in various proteins found in neuronal cells is responsible for neurodegenerative diseases such as Huntington’s chorea, which currently has no cure and no treatment to slow down its development.
Benedetta Bolognesi, leader of the Protein Phase Transitions in Health and Disease Group at the Institute for Bioengineering of Catalonia (IBEC), and Xavier Salvatella, leader of the Laboratory of Molecular Biophysics at the Institute for Research in Biomedicine (IRB Barcelona), lead PolySTOP. The project will combine the methodology developed by Bolognesi’s lab to measure these amino acid expansions in vivo —which will apply to the more than 300 mutations of the Htt-Nt protein responsible for Huntington’s disease— with the experience of Salvatella’s team in the structural study of these expansions and the design of peptides.
“Our methodology allows us to analyse the propensity of thousands of PolyQ sequences to produce amyloid plaques. It is a systematic way to measure how these chains and their ‘adjacent regions’ impact aggregation. With this we can obtain ‘mutational landscapes’ that will allow us to understand what exactly these areas do in the aggregation process. Xavier’s team will then be able to study their structure and design peptides that can bind to glutamines and control their aggregation,” explains Dr Bolognesi. “This may offer therapeutic alternatives not only for Huntington’s, but also for other neurodegenerative diseases that are currently untreatable.“