Analysing the role of mitochondrial calcium in neurodegeneration at Medical Research Council (Cambridge) on FindAPhD.com

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Dr A J Whitworth No more applications being accepted Funded PhD Project (UK Students Only)

Cambridge United Kingdom Cell Biology Genetics Molecular Biology Neuroscience

Mitochondrial Biology Unit, Medical Research Council (Cambridge)

About the Project

Mitochondrial calcium plays a key role in a wide array of cellular homeostatic processes and has been linked to causing neurodegeneration [1]. The research in our lab focusses on understanding the causes of various neurodegenerative diseases, such as Parkinson’s and Huntington’s Disease, to identify potential therapeutic interventions. We take a multi-disciplinary approach to combine molecular cell biological techniques with the powerful genetic model, Drosophila.

We have developed a genetic toolkit to manipulate mitochondrial calcium flux in Drosophila [2]. Using these, we have found that reducing mitochondrial calcium uptake is beneficial in a range of neurodegenerative disease models [3]. This project will further characterise this interaction as a potential therapeutic avenue, and to understand the molecular basis behind the sensitivity of these disease conditions to mitochondrial calcium.

The experimental aims will encompass a wide range of techniques including Drosophila genetics, live-imaging techniques to analyse mitochondrial calcium dynamics, as well as behavioural and neuro-functional assays. Molecular techniques will also be employed to analyse cellular changes, in particular to the metabolic pathways and autophagy, that underpin the consequences of dysregulated mitochondrial calcium handling. Insight into these pathogenic and homeostatic mechanisms will give us a greater understanding of the causes of these diseases and illuminate potential therapeutic avenues.

Competitive applicants will have a high degree classification from a leading university, with excellent knowledge and experience within the fields of cell biology, genetics and the use of small model organisms in modelling human disease. They will also have substantial lab experience in molecular, cell biology and/or genetic techniques.

Keywords

General: Mitochondria, Calcium, Neurodegeneration

More specific: Parkinson’s disease, Huntington’s disease, Drosophila, in vivo, autophagy

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

Funding Notes

This studentship is available for UK/Irish citizens or UK permanent residents. Details about funding and eligibility are available on our website: https://www.mrc-mbu.cam.ac.uk/postgraduate-studies
The start date: October 2024.
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: https://www.mrc-mbu.cam.ac.uk/postgraduate-studies.

References

1. Granatiero V, De Stefani D, Rizzuto R. Mitochondrial Calcium Handling in Physiology and Disease. Adv Exp Med Biol. 2017;982:25-47.
doi:10.1007/978-3-319-55330-6_2
2. Tufi R, Gleeson TP, von Stockum S, Hewitt VL, Lee JJ, Terriente-Felix A, Sanchez-Martinez A, Ziviani E, Whitworth AJ. Comprehensive Genetic Characterization of
Mitochondrial Ca(2+) Uniporter Components Reveals Their Different Physiological Requirements In Vivo. Cell Rep. 2019;27(5):1541-50 e5.
doi:10.1016/j.celrep.2019.04.033
3. Twyning MJ, Tufi R, Gleeson TP, Kolodziej KM, Campesan S, Terriente-Felix A, Collins L, De Lazzari F, Giorgini F, Whitworth AJ. Partial loss of MCU mitigates
pathology in vivo across a diverse range of neurodegenerative disease models. Cell Rep. 2024;43(2):113681. doi:10.1016/j.celrep.2024.113681