CIBSS speaker and researcher at the University of Freiburg Prof. Dr. Claudine Kraft has been awarded a Synergy Grant by the European Research Council (ERC). Over six years, she and her international partners will receive a total of €10 million euros for their project “DegrAbility: On the Degradability of Protein Aggregates by Autophagy”. The aim of the project is to better understand why the cellular recycling process known as autophagy is unable to clear certain types of protein aggregates and to harness this knowledge to improve autophagy in ageing and disease. Kraft will receive around €3.33 million euros for her part of the project.
· Press Release
ERC Synergy Grant for Prof. Dr. Claudine Kraft
CIBSS speaker Prof. Dr. Claudine Kraft is part of a team receiving an ERC Synergy Grant of ten million euros for her research on how autophagy degrades large protein aggregates in health and disease.
Prof. Dr. Claudine Kraft. Photo: Jürgen Gocke / University of Freiburg
Interaction with the aggregate stalls autophagy machinery
The cells in our body are constantly rebuilding themselves: components that are damaged or not needed any longer are cleared and the basic building blocks are recycled. Aggregated proteins are removed by a process named autophagy. In ageing and neurodegenerative diseases such as Alzheimer’s disease, autophagy is not functioning properly anymore. As a consequence, large protein aggregates accumulate and cause damage to the cell.
While aggregates remain in a liquidlike, more dynamic state, the autophagy machinery recognizes them and triggers the clearance process. At some point however, aggregates stiffen and are no longer efficiently removed by autophagy. “Until now, it was thought that the properties of the aggregate determine whether it can be broken down or not,” says Kraft. “But early results from my group’s research and that of my two partners suggest that the problem is actually the interaction between the autophagy machinery and the aggregate.” Her team could previously show that this molecular interaction needs to remain dynamic – once the aggregate is too tightly bound, autophagy stalls and aggregates accumulate.
The “DegrAbility” project will uncover the mechanisms that control this process with the aim to explore potential strategies for ways to release the stalling. This might benefit patients suffering from disabling neurodegenerative diseases and other age-related conditions by clearing up toxic aggregates such as plaques in Alzheimer’s disease.
Combining forces to understand determinants for efficient autophagy
Kraft teamed up with Prof. Dr. James Hurley at the Department of Molecular & Cell Biology at the University of California Berkeley, USA, and Prof. Dr. Sascha Martens at the Max Perutz Labs at the University of Vienna, Austria. Hurley’s expertise in high-resolution structural analyses will make the interaction between aggregate and autophagy machinery visible on the atomic level, while Martens will use biochemical reconstitution systems to test and manipulate them at the molecular level. Kraft will employ tunable cell models to understand how these mechanisms control autophagy in a biological setting and which implications this has for cell function.
Kraft emphasizes: „The expertise we are leveraging is only possible thanks to our three complementary approaches.” With “DegrAbility”, the researchers and their teams hope to contribute to the development of therapeutic strategies targeting toxic protein aggregates. “Our ultimate goal is to identify novel mechanisms that could be used in the future to specifically promote protein degradation in ageing and disease processes,” explains Kraft.
About Claudine Kraft
Claudine Kraft is a professor at the Institute of Biochemistry and Molecular Biology, University of Freiburg. Her group investigates the molecular mechanisms of autophagy, the fundamental recycling process within cells. They study how cells identify and degrade internal components, contributing to insights into diseases such as Alzheimer’s and cancer. She has been a professor at the University of Freiburg since 2017, a member of CIBSS since 2019 and a part of the CIBSS leadership team since 2025. She has also had research positions at the University of Vienna, ETH Zurich and University of Manchester. Kraft holds a European Research Council (ERC) Consolidator Grant for the project AutoClean (2018–2025) and is a principal investigator in several collaborative research initiatives, including CRC 1177 Autophagy, CRC 1381 Dynamic Organization of Protein Machineries, and the Research Training Group RTG 2606 ProtPath.
ERC Synergy Grants
The ERC Synergy Grant supports teams of two to four researchers working together and combining different skills and resources to tackle ambitious research problems. This year, 66 out of 712 submitted project proposals were selected for funding.