Analysing the detrimental effects of polyglutamine expansion

All proteins must fold to, and maintain, their correct three-dimensional shape to function. However, small changes in the sequence of the protein can disrupt this process, leading to protein aggregation and disease. The polyglutamine repeat family of proteins are involved in a range of neurodegenerative disorders, the most common being Huntington s disease. In healthy individuals up to 37 glutamine repeats can be tolerated in these proteins, however, in diseased individuals glutamine repeats in excess of 45 are always observed. In this project we will study the conformational properties of the polyglutamine tract to determine how polyglutamine tract expansion leads to protein misfolding, aggregation and disease.