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Targeting mitochondrial dynamics to prevent Parkinson’s disease


Project Description

A common feature of Parkinson’s disease (PD) is the presence of alpha-synuclein protein aggregates in the brains of affected patients. These aggregates damage dopaminergic neuronal cells by increasing oxidative stress. It is well established that oxidative stress causes breakdown of the mitochondrial network, leading to neuronal cell death and disease progression. Understanding of how oxidative stress triggers damage to the mitochondrial network is essential for the development of novel treatments for PD, for which currently there is no cure. We have recently demonstrated that inhibition of a stress-activated ion channel, known as the TRPM2 channel, prevents breakdown of the mitochondrial network (refs 1-2) as well as the death of pancreatic beta cells.

Our unpublished work suggests a similar mechanism to underlie the death of dopaminergic neuronal cells. In an attempt to translate this knowledge to novel therapies, we have generated bespoke biologics (antibodies, recombinant proteins and peptides) capable of blocking the TRPM2-mediated mechanisms that kill these neuronal cells. The aim of the project is to use both in vitro and in vivo (preclinical) approaches to investigate the potential of these agents for treatment of PD.

Techniques to be used: General molecular biology, cell biology and protein chemistry techniques; confocal, super-resolution and electron microscopy; calcium imaging; in vitro and vivo models for Parkinson’s disease.



Funding Notes

University of Leeds research scholarships (View Website) for UK students
and

Self-funding: applications accepted throughout the year

References

For publications from Sivaprasadarao’s group, visit:
https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/135/professor-asipu-sivaprasadarao
For publications of Bon's group, visit:
https://medicinehealth.leeds.ac.uk/medicine/staff/1194/dr-robin-s-bon

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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