Baden-Württemberg Foundation Funds Research Project on Protein Aggregation
22 February 2017
Heidelberg molecular biologist Prof. Dr Bernd Bukau has been awarded a grant of approximately 280,000 euros from the Baden-Württemberg Foundation for a research project on the neurodegenerative disorder of Parkinson's disease. The project is a continuation of the previous work by Prof. Bukau and his team on the dissolution of protein aggregates that are responsible for a number of different diseases, including Alzheimer's. The experiments are focussed on so-called heat shock proteins (Hsp), which cells produce to counteract the aggregates. The Heidelberg University researchers expect their work to provide new insights into the origin and prevention of Parkinson's disease. The foundation is funding the project for three years as part of its "International Top Research III" programme.
In the project entitled "Mechanism of alpha-synuclein amyloid fibril disaggregation by molecular chaperones", the researchers will be investigating the Hsp70 class of heat shock proteins. These proteins are molecular chaperones that protect other proteins from aggregating or that isolate and repair aggregated proteins. The researchers want to understand how Hsp70 affects the ɑ-synuclein protein aggregates that are specific to Parkinson's. In their earlier work, Bukau's team was able to demonstrate that Hsp70 is able to dissolve aggregates of the ɑ-synuclein protein. The team now plans on delving into the molecular basis of this activity.
Dutch researcher and Bukau team member Dr Anne Wentink will use methods from biochemistry and structural biology to detail more closely the binding of Hsp70 to a complete three-dimensional structure of the ɑ-synuclein amyloid. "A precise understanding of the binding mechanisms should give us valuable information on the cell's inherent abilities to counteract protein aggregates, thus leading to new approaches in developing medications to treat Parkinson's," explains Prof. Bukau. Structural biologist Prof. Dr Helen Saibil of the University of London will collaborate with the team of Heidelberg researchers. She will use electron microscopy to visualize Hsp70 binding to ɑ-synuclein proteins at a high resolution in the nano range.
Bernd Bukau is Director of the Center for Molecular Biology of Heidelberg University (ZMBH) as well as a researcher with the German Cancer Research Center (DKFZ). In the interdisciplinary field of biochemistry and molecular biology, he studies the quality control mechanisms that cells use to monitor the process of protein folding and to correct defective proteins – of crucial importance to the function of human cells. Prof. Bukau was awarded the 1999 Leibniz Prize from the German Research Foundation for his groundbreaking work in this area.
The "International Top Research" programme of the Baden-Württemberg Foundation is designed to support cooperation with outstanding foreign scientists.