Activating Parkin to treat Parkinson’s disease

Activating Parkin to treat Parkinson’s disease

Project details

The E3 ubiquitin ligase Parkin is activated upon mitochondrial stress to initiate the destruction of damaged mitochondria. The last 5 years have provided a detailed molecular picture of how Parkin transitions from an inactive to an active E3 ligase. Importantly, mutations in Parkin lead to early-onset Parkinson’s disease, a progressive neurodegenerative disorder for which there are no treatments. Our recent work has revealed how Parkin activators may become new medicines to delay or stop the onset of disease (Gladkova Nature 2018, xxx). 

In your project, you will build on these discoveries, to develop small molecule activators of Parkin, using chemical, biochemical, biophysical and structural biology techniques. This will be integrated in larger efforts to understand physiology of Parkin, to exploit its promise for drug discovery.

Protein structure
The structure of activated phospho-Parkin bound to phospho-ubiquitin

About our research group

My lab moves to the Institute in November 2018 from the MRC Laboratory of Molecular Biology in Cambridge, UK. We will form the core of a new division that focusses on understanding ubiquitin and ubiquitin-like modifications, and as such integrate with and enable the many labs and divisions at the Institute, to uncover new links and discover new pathways regulated by ubiquitination. A particular interest will be on neurodegenerative diseases, including Parkinson’s disease, for which exciting links to inflammation, a core strength of the Institute, are currently emerging. Eventually, we hope to turn our mechanistic insights into first medicines, that delay or stop the onset of neurodegeneration in human patients.  

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