Principal Investigators

    Dr F Buss


    University of Cambridge

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    Investigating the role of Myosin VI in quality control of mitochondria linked to Parkinson's disease pathology

    Source of funding information


    Total sum awarded (Euro)

    € 733,816

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders


    Research Abstract

    In this project we will investigate the molecular function of the actin-based motor protein myosin VI in mitochondrial quality control. Defects in mitochondrial turnover are closely linked to Parkinson’s disease (PD), the second most common neurodegenerative disorder. A hereditary form of PD is caused by mutations in the E3 ubiquitin ligase Parkin; this protein has been shown to mediate selective autophagy of damaged mitochondria, called mitophagy. Several lines of evidence and data from published large-scale whole genome studies suggest a functional link between Parkin and myosin VI and its cargo adaptors. To test this hypothesis and analyse the link between myosin VI and Parkin in more detail we will use in situ proximity labeling and a combination of confocal fluorescence microscopy, live cell and super-resolution microscopy as well as electron microscopy. To determine the requirement of myosin VI and its adaptor proteins for Parkin-mediated mitophagy, we will use siRNA KD cells, KO cells created by CRISPR/Cas9 genome editing, primary fibroblasts and neurons from our myosin VI KO mouse as well as iPS cells generated from human PD patient fibroblasts. In addition we will employ multiple approaches to assess whether loss of myosin VI or its adaptor proteins affects mitophagy and thereby leads to an accumulation of damaged mitochondria with reduced function.

    Lay Summary

    Further information available at:

Types: Investments > €500k
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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