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Ca2+ signalling in neurodegeneration and Alzheimer's disease


Key facts

Type of research degree
Application deadline
Ongoing deadline
Project start date
Thursday 1 October 2020
Country eligibility
International (open to all nationalities, including the UK)
Competition funded
Source of funding
University of Leeds
Professor Ian Hope
School of Biology
<h2 class="heading hide-accessible">Summary</h2>

Human variants of the ryanodine receptor, the main intracellular calcium ion channel, could be responsible for Alzheimer&amp;rsquo;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.

<h2 class="heading hide-accessible">Full description</h2>

<p>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&rsquo;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&rsquo;s disease, such as the calcium hypothesis, need to be pursued.</p> <p>Such a difficult subject to research demands a good experimental model. <em>Caenorhabditis elegans</em> 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&rsquo;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 <em>C. elegans </em>is very much relevant.</p> <p>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&rsquo;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 <em>C. elegans </em>will allow assessment of consequences for amyloid aggregation. Findings could illuminate mechanisms underlying Alzheimer&rsquo;s Disease aetiology, could provide further avenues for investigation of the causes of neural degeneration, and could deliver novel strategies for treatment development.</p>

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &ldquo;Ca2+ signalling in neurodegeneration and Alzheimer&#39;s disease&rdquo; as well as&nbsp;<a href="">Prof. Ian Hope</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<h2 class="heading">Funding on offer</h2>

<p>We would encourage you to review the linked scholarships below and apply for any that are open to you.&nbsp; We also welcome applications from self-funded students.&nbsp;&nbsp;</p> <p>If you have any questions about funding please email <a href=""></a>&nbsp;</p>

<h2 class="heading">Contact details</h2>

<p>For further information please contact the <a href="">Graduate School Office</a> or<br /> e:&nbsp;<a href=""></a>, t: +44 (0)113 343 2889.</p>

<h3 class="heading heading--sm">Linked funding opportunities</h3>