Grant: Operating Grant

Proteins are made as linear molecules which must fold into stable three-dimensional structures, and find their correct workplace within cells. Defects in protein folding are the underlying causes of neurodegenerative syndromes including Parkinson and Alzheimer diseases, and genetic disorders such as cystic fibrosis. The molecular chaperones are specialized proteins which help other proteins to fold, and are critical cellular defenses against misfolding. A key chaperone is Hsp70, which has important roles in promoting folding but also in selecting proteins for degradation. Importantly, Hsp70 activity depends on co-chaperone proteins which regulate its action. My focus is on the two major co-chaperones, DnaJA1 and DnaJA2, and how they work together with Hsp70. The experimental approach follows two inter-related directions: understanding the biochemical mechanisms by which Hsp70 and its co-chaperones act on proteins, and investigating the cellular division of labour between the co-chaperones. Both of these research directions will be essential to understand and ultimately address the serious health challenges posed by protein misfolding diseases.