Name of Fellow

    Dr Yu Ye



    Wellcome Trust

    Contact information of fellow


    United Kingdom

    Title of project/programme

    Resolving ubiquitin-dependent degradation of misfolded proteins using advanced single-molecule techniques.

    Source of funding information

    Wellcome Trust

    Total sum awarded (Euro)

    € 338,950

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders


    alzheimer | Neurodegen

    Research Abstract

    My proposed research seeks to understand the links between degradation of protein aggregates and the ubiquitin-proteasome pathway. The project entails three goals. The first goal involves establishing a fluorescence-based system to detect individual interactions between aggregates and proteasomes. To achieve this, I will initially receive training on proteasome purification and examine how to modify proteins with specific ubiquitin chains. Subsequently, I will explore different fluorescence labe lling systems and optimise a labelling strategy for protein aggregates and the proteasome without disrupting their integrity. The fluorophores selected should be bright and photostable to be compatible with the single-molecule instruments. This single-molecule fluorescence system will be used to establish a method that can reveal interactions between individual protein aggregates and a single proteasome to determine the efficiency of degradation for different types of aggregates. The second goal will focus on aggregate degradation in cells using three-dimensional superresolution imaging. Heterogeneous interaction between aggregates and proteasomes can be resolved to determine whether certain types of aggregates can inhibit the proteasome. Finally, I will focus on cell lines with mutations on key Parkinson’s disease-related genes, and establish whether aggregate degradation is affected. Identifying altered degradation in these cells will relate proteasome functions directly to disease s tates.

Types: Fellowships
Member States: United Kingdom
Diseases: Parkinson's disease & PD-related disorders
Years: 2016
Database Categories: N/A
Database Tags: N/A

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