FindAPhD Weekly PhD Newsletter | JOIN NOW FindAPhD Weekly PhD Newsletter | JOIN NOW

Investigating mechanisms of mitochondrial quality control in Drosophila models of neurodegeneration


   Mitochondrial Biology Unit

   Thursday, January 05, 2023  Competition Funded PhD Project (Students Worldwide)

About the Project

PINK1 and Parkin (PRKN), two genes linked to Parkinson's disease, have been strongly linked to the selective degradation of mitochondria (mitophagy). However, much of our current understanding comes from in vitro studies, and we still have a poor understanding of this process in a physiological context in vivo [1]. PINK1 phosphorylates ubiquitin (pS65-Ub) on mitochondria to trigger mitophagy. We have recently developed protocols to detect PINK1 activity and monitor mitophagy under physiological conditions in vivo in Drosophila [2]. With these quantitative mass spectrometry and immunodetection methods, we can now deeply analyse the spatiotemporal activation of the pathway in vivo by monitoring the level and localisation of pS65-Ub.

This project will investigate the mechanisms of Pink1 activation in Drosophila, in particular analysing the tissue specific distribution of pS65-Ub and mechanisms of degradation. Using state-of-the-art super-resolution microscopy, the project will also probe the sub-cellular distribution of pS65-Ub, addressing whether it may associate with sub-mitochondrial compartments in vivo. Importantly, we will also investigate the physiological mechanisms of stimuli. We are also interested in understanding the role that mitochondrial calcium plays in quality control processes [3], and this project would provide an opportunity to collaborate on these investigations. This project will shed new light on important mechanisms of mitochondrial quality control and potentially identify new targets for therapeutic interventions.

Keywords

General: Mitochondria, Neurodegeneration, Mitophagy

More specific: PINK1, quality control, mass spectrometry, super-resolution microscopy, calcium, Drosophila

Research Group: https://www.mrc-mbu.cam.ac.uk/research-groups/whitworth-group


Funding Notes

Details about funding and eligibility are available on our website: View Website
The start date: October 2023.
The University's application portal opens on 15 September 2022.
Applications will not be accepted via the enquiry email address. This address is to ask the supervisors for further information about the project. For details on how to apply please see our postgraduate studies webpage: View Website.

References

[1] PINK1/Parkin mitophagy and neurodegeneration-what do we really know in vivo?
Whitworth AJ, Pallanck LJ.Curr Opin Genet Dev. 2017 Jun;44:47-53. doi: 10.1016/j.gde.2017.01.016. PMID: 28213158
[2] https://doi.org/10.1101/2021.06.10.447841
[3] Comprehensive Genetic Characterization of Mitochondrial Ca2+ Uniporter Components Reveals Their Different Physiological Requirements In Vivo.
Tufi R, Gleeson TP, von Stockum S, Hewitt VL, Lee JJ, Terriente-Felix A, Sanchez-Martinez A, Ziviani E, Whitworth AJ.Cell Rep. 2019 Apr 30;27(5):1541-1550.e5. doi: 10.1016/j.celrep.2019.04.033. PMID: 31042479

Email Now


Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.

PhD saved successfully
View saved PhDs