University of Leeds Featured PhD Programmes
Engineering and Physical Sciences Research Council Featured PhD Programmes
King’s College London Featured PhD Programmes

Ca2+ signalling in neurodegeneration and Alzheimer’s disease

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Human variants of the ryanodine receptor, the main intracellular calcium ion channel, could be responsible for Alzheimer’s disease. Caenorhabditis elegans provides a powerful genetic system for laboratory study and has a short life span making this species ideal for investigation of this hypothesis.

Full description
Dramatic changes in cytosolic calcium ion concentrations are central to neural excitation. However, intracellular calcium ion levels also have other crucial regulatory roles, vital for the long-term health and function of nerve cells. During nerve cell excitation, the ryanodine receptor is the key channel for controlled release of calcium ions from the principal source, the endoplasmic reticulum. Many variants of the ryanodine receptor present in the human population retain calcium channel function but with modified opening properties which alter cytosolic calcium ion levels. Subtly altered calcium ion concentrations are likely to have negative consequences for nerve cells over time and there is some evidence of a link between ryanodine receptor function and Alzheimer’s disease. Given the lack of success in clinical drug trials aimed at treating this condition, so far, research on alternative explanations for the root cause of Alzheimer’s disease, such as the calcium hypothesis, need to be pursued.

Such a difficult subject to research demands a good experimental model. Caenorhabditis elegans provides a powerful genetic system for laboratory study with a short life span that makes this animal ideal for investigation of age-related conditions like Alzheimer’s disease. Although a nematode may appear only distantly related to us, the remarkable level of conservation between animals at the cell biological and molecular genetic levels means C. elegans is very much relevant.

Through the proposed project, the potential for subtle calcium ion dyshomeostasis, arising from aberrant ryanodine receptor function, to contribute to age-related neuronal degeneration, such as associated with Alzheimer’s Disease, will be assessed. The consequences of minor ryanodine receptor dysfunction, generated through CRISPR-Cas9 genome editing, will be determined with respect to neural function, nerve cell integrity, and amyloid aggregation. Neural function will be assessed with respect to memory and sensory activity. Neural degeneration and synaptic strength will be examined morphologically in GFP-labelled cells and by electron microscopy. Expression of amyloid-beta peptide in C. elegans will allow assessment of consequences for amyloid aggregation. Findings could illuminate mechanisms underlying Alzheimer’s Disease aetiology, could provide further avenues for investigation of the causes of neural degeneration, and could deliver novel strategies for treatment development.

Funding Notes

We would encourage you to review the linked scholarships here View Website apply for any that are open to you. We also welcome applications from self-funded students.
Formal applications for research degree study should be made online through the University's website. Please state clearly in the research information section that the research degree you wish to be considered for is “Ca2+ signalling in neurodegeneration and Alzheimer's disease” as well as Prof. Ian Hope as your proposed supervisor.
If you have any questions about funding please email

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

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully

FindAPhD. Copyright 2005-2020
All rights reserved.