Many diseases are associated with the formation of aberrant protein aggregates, yet controlled oligomerization provides advantages for biological structure and function. Among them are neurodegenerative diseases like Alzheimer’s or Huntington’s that are to date incurable and pose one of the grand challenges for society. Despite tremendous progress it remains unclear what causes neuronal toxicity. Different types of assemblies (oligomers, fibrils, amyloid-like aggregates, …) have been identified, but the underlying molecular mechanisms of formation remain elusive. Phase transitions are suggested to play a key role in protein aggregation of intrinsically disordered proteins such as Huntingtin. Still, direct evidence of these transitions in patient brains is missing. What role, if any, does liquid-liquid phase separation play in neurodegeneration? What molecular and cellular determinants influence these transitions? To answer these questions, a better definition of the structural and functional features of protein assemblies is necessary, including their material properties. Exploring different Huntington’s model systems, from in vitro to neuronal cells will provide maximal insight. You will use our imaging toolbox and other nanotechnology available in the department to tackle this challenge. You will also apply machine learning and correlation analysis to fully exploit our recently developed 3D quantitative phase imaging for disease monitoring. As an integral part of our team, you will have the opportunity to e.g., design new optics or to establish new synthetic cell model systems for neurodegenerative disease. We welcome applications from people with diverse backgrounds. Depending on your scientific profile and interests, the specific focus of the project can be adjusted.
This project is in collaboration with Hilal Lashuel (EPFL) and Aleksandra Radenovic (EPFL).
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