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Dissecting endolysosomal intracellular trafficking defects in Parkinson’s disease


Institute of Healthy Ageing

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Dr Kerri Kinghorn , Prof L Partridge No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

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Applications are invited for a Rosetrees Trust funded PhD studentship hosted at the UCL Institute of Healthy Ageing

Mutations in genes mapping to endolysosomal intracellular trafficking pathways are increasingly being implicated in Parkinson’s disease (PD). Indeed, heterozygous mutations in the lysosomal storage disorder gene GBA1 are considered the greatest genetic risk factor for PD. We have previously developed successful fly models of PD (Kinghorn et al. Brain 2015 138:1801-16; Kinghorn et al. J. Neuroscience 2016 36:1165-11670), which have provided crucial insights into the pathogenic mechanisms leading to neurodegeneration. Flies lacking GBA activity display lysosomal-autophagic defects and mitochondrial dysfunction, and are rescued by the mTOR inhibitor rapamycin.

The aim of this post is to study the pathogenic mechanisms linking mutations in lysosomal storage disorder-linked PD genes to the development of neurodegeneration, using novel loss-of-function Drosophila models, in addition to advanced genetic techniques. We will focus on the endolysosomal-trafficking defects, as well as on common downstream pathogenic mechanisms, with a view to identifying new therapeutic targets in PD.

The underlying pathogenic mechanisms will be investigated in the PD fly models using fly genetics and pharmacological treatments, fly phenotyping, including molecular and biochemical assays such as qPCR and western blotting, survival assays, immunostaining and microscopy, gene-specific functional read-outs, and omics analyses as required. This studentship will provide excellent training in neuroscience and experimental approaches to neurodegeneration.

Entry requirements: applicants are required to hold a first or upper-second class UK Bachelor’s degree in a relevant subject (or international equivalent), or a recognised Master’s degree.

Informal enquiries: contact Dr Kerri Kinghorn, UCL Institute of Healthy Ageing [Email Address Removed].

Application procedure: Application is by CV and covering letter emailed to [Email Address Removed].

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Funding Notes

A student stipend of £17,009 per annum plus tuition fees at Home(UK)/EU rate and research/travel costs.

For EU students accepting a place on a programme for entry in the academic year 2020/21 the UK Government has confirmed arrangements that will allow them to pay the same tuition fees as UK students for the duration of their enrolment on that specific programme (subject to any annual increase in accordance with the applicable terms and conditions and the UCL fees schedule).
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