Tau je protein asociovaným s mikrotubuly, vnitřně narušeným, převážně lokalizovaným v neuronech, který se podílí na neurodegenerativních poruchách, jako je Alzheimerova choroba.
Předběžná náplň práce v anglickém jazyce
Tau is an intrinsically-disordered microtubule-associated protein, predominantly localized in neurons, which is involved in neurodegenerative disorders, such as the Alzheimer’s disease. Tau is known to stabilize microtubules and regulate the function of many other microtubule-associated proteins. What underlies these regulatory mechanisms on the molecular level is not fully understood. It has been shown recently that tau can form compartments through liquid-liquid phase separation in solution and ordered domains on the microtubule surface presumably also through phase separation. How do these processes regulate other cytoskeletal proteins and processes is however unknown.
In this project we will explore the regulatory roles of the ordered domains of tau and other intrinsically disordered cytoskeletal proteins emerging on the surface of cytoskeletal filaments. We will generate these domains on filaments in vitro and probe i) the interactions between domains of different intrinsically disordered proteins, and ii) the interactions of other proteins associated with cytoskeletal filaments, such as motor proteins or filament-severing enzymes, with these domains. Additionally / alternatively, we will explore the roles of these domains in the stabilization of cytoskeletal filaments and in generation of forces between cytoskeletal filaments. We will image the explored systems with single molecule resolution using total internal reflection fluorescence (TIRF) microscopy and probe the generated forces using optical tweezers. With this project we aim to clarify some of the regulatory mechanisms mediated by tau and other unstructured cytoskeletal proteins.
- zadáno a potvrzeno stud. odd.