Protein misfolding is at the heart of several diseases including neurodegeneration, which collectively affect 7 million people in Europe, costing the healthcare systems €130 billion per year. Proteins with complex primary sequences such as long stretches of glutamine (polyQ), adopt non-native conformations and aggregate. The disease-causing protein may be expressed at equal levels in a variety of tissues, yet misfolding occurs only in few cell-types – in most cases neurons. Defining the relevant cellular context that impacts tissue-specific manifestation of protein misfolding is of paramount importance to address the basis of neurodegeneration paving avenues for therapeutic intervention. Novel therapies will then help us to tackle/ mitigate the age-related health concerns faced by the Western society.
The overall objective of this project is to identify why neurons are susceptible to protein misfolding diseases. We will address this objective by combining new animal models and cell cultures, along with state-of-the-art genomic technologies.