Proteins can misfold and self-assemble into highly ordered fibrillar amyloid structures with toxic effects, a phenomenon that is linked to about 40 human diseases, including type-2 diabetes and the neurodegenerative disorders Parkinson disease and Alzheimer's disease (AD). Molecular chaperones play important roles in preventing protein misfolding and its potentially harmful consequences. Deterioration of molecular chaperone systems upon ageing are thought to underlie age-related neurodegenerative diseases and augmenting their activities could have therapeutic potential. Our research focuses on the molecular mechanisms of dementia relevant chaperone domain BRICHOS against self-assembly of proteins and peptides, e.g. Aβ42 and Tau associated with AD and islet amyloid polypeptide (IAPP) associated with type 2 diabetes, and the augmentation of chaperone activity for future clinical applications.

Spider silk has amyloid-like properties and is one of the toughest biomaterials that exist. Spider silk proteins, spidroins, undergo a rapid transformation from highly concentrated soluble dope with helical and disordered conformations to solid β-strand-rich fibers. During spidroin self-assembly, the long, repetitive regions are converted into β-sheet crystals connected by disordered linkers, and this process is regulated by comparatively small and globular N and C-terminal domains. Our research aims to find out the importance of amyloid-like structure formation during the fast spider silk assembly process, and the underlying mechanisms of structural transformation. In particular we are interested to produce and study a specific motif present in certain repetitive regions in its soluble and fibrillar state.

In these projects, the student will produce challenging proteins and peptides recombinantly, and study the properties by biochemical and biophysical methodologies.

You are welcome to send further contact for project details.