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  Evaluating the therapeutic potential of leptin-based hexamers in neurodegenerative disease


   School of Medicine

  , ,  Sunday, June 30, 2024  Self-Funded PhD Students Only

About the Project

Translation of basic research into Alzheimer’s disease (AD) therapies is hindered by our inability to turn promising lab results into drugs that can be taken by patients. One way of addressing this, is to use compounds that we know are safe for human use, in pre-clinical studies examining the network properties that degrade in AD. Our previous work has identified that fragments of the metabolic hormone, leptin, prevent AD-related neurodegeneration and improve the type of memory that is first impaired in AD. In this project, we will extend this work to examine how leptin-based fragments affect a key pathological trait of AD: build-up of neurofibrillary tangles comprising hyper-phosphorylated tau. 

Tau modification and its accumulation in neurons strongly correlate with cognitive deficits and synaptic deficits in early AD. In healthy neurons, tau is concentrated in axons, but phosphorylation of tau in AD, targets it to synapses where it causes synaptic dysfunction. Consequently, limiting tau effects on synaptic function may prevent the synaptic abnormalities underlying AD-related cognitive deficits. However, our understanding of how tau impairs synaptic function, and how tau-related synaptic dysfunction can be targeted therapeutically is limited. Here, we propose to assess the neuroprotective actions of leptin-based fragments in tau models of dementia. This will include using a combination of electrophysiology, and confocal imaging techniques to assess beneficial effects in tau models of synaptic pathology. A range of behavioural tasks will be used to determine effects on hippocampus-dependent memory processes, whereas the synaptic expression of leptin receptors and associated targets will be determined in rodent and human tissue using state-of the art array tomography.

This study will facilitate the advancement of leptin-based drugs as a potential treatment for AD.

For informal enquiries about the project, contact Prof Jenni Harvey,

 

For general enquiries about the University of Dundee, contact

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.

QUALIFICATIONS

Applicants must have obtained, or expect to obtain, a UK honours degree at 2.1 or above (or equivalent for non-UK qualifications), and/or a Masters degree in a relevant discipline. For international qualifications, please see equivalent entry requirements here: www.dundee.ac.uk/study/international/country/.

English language requirement: IELTS (Academic) overall score must be at least 6.5 (with not less than 5.5 in reading, listening, speaking and 6.0 in writing). The University of Dundee accepts a variety of equivalent qualifications and alternative ways to demonstrate language proficiency; please see full details of the University’s English language requirements here: www.dundee.ac.uk/guides/english-language-requirements.

 

APPLICATION PROCESS

Step 1: Email Prof Jenni Harvey, to (1) send a copy of your CV and (2) discuss your potential application and any practicalities (e.g. suitable start date).

Step 2: After discussion with Prof Harvey, formal applications can be made via our direct application system. When applying, please follow the instructions below:

Candidates must apply for the Doctor of Philosophy (PhD) degree in Medicine (4 year) using our direct application system: apply for a PhD in Medicine.

Please select the study mode (full-time/part-time) and start date agreed with the lead supervisor.

In the Research Proposal section, please:

-         Enter the lead supervisor’s name in the ‘proposed supervisor’ box

-         Enter the project title listed at the top of this page in the ‘proposed project title’ box

In the ‘personal statement’ section, please outline your suitability for the project selected.

Biological Sciences (4) Medicine (26)

Funding Notes

There is no funding attached to this project. The successful applicant will be expected to provide the funding for tuition fees and living expenses, via external sponsorship or self-funding.

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