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The University of Southampton
Biological Sciences

Research project: Investigating mitochondrial-derived vesicles and their relationship to Parkinson's disease pathology

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Parkinson’s predominantly manifests during the course of ageing, leading to neuronal cell death in the brain, which results in cognitive and motor impairment. Mitochondrial damage and defects in associated repair pathways are one of the key drivers of disease pathology. This studentship will investigate physiological mechanisms that coordinate mitochondrial quality control, focusing on pathways regulated by the proteins PINK1 and Parkin, which are associated with genetic causes of Parkinson’s.

Our group has recently identified the endosomal adaptor and innate immune regulator Tollip as an essential coordinator of a Parkin-dependent mitochondrial derived vesicle (MDV) pathway. The MDV pathway is a repair mechanism that traffics damaged mitochondrial cargo to the lysosome, to preserve the integrity of the mitochondrial network and to limit cell death as a result of oxidative stress. This projects aims to elucidate the functional mechanisms associated with a Tollip-Parkin interaction and in particular how this complex regulates the transport of MDVs to the lysosome. In addition, this project will evaluate these mitochondrial quality control mechanisms in a model that more closely resembles Parkinson’s. This will entail use of neurons harvested from Thy1-SNCA mice, which overexpress alpha-synuclein, and use of alternative synuclein models developed in established cell lines. These experiments will give insight into how mitochondrial quality control is impaired following Synuclein-induced stress. Our overall objective is to determine how a Tollip-Parkin association regulates mitochondrial quality control and whether this complex is relevant in a model more closely related to disease.

Principle Investigator: David Tumbarello

Co-supervisor: Roxana Carare

PhD Student: Naomi Thorne

Funding provider:

The Gerald Kerkut Charitable Trust and University of Southampton

Funding dates: 28/09/2020 – 28/03/2024

Related research groups

Molecular and Cellular Biosciences
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