Investigating the Molecular Consequences of Impaired Macroautophagy on the Development of Ataxia

Newcastle of University

Translational and Clinical Research Institute

Project Description

Autophagy plays a prominent role in neurodegeneration, inflammatory conditions, ageing and cancer. In humans, congenital autophagy defects are extremely rare although some cases are reported in association with diverse neurological and neurodevelopmental problems. Given the emergence of this group of genetic disorders, there is a need to understand the role of autophagy in neural integrity, particularly if autophagy-augmenting therapeutics are to be developed.

We have identified several families with defective macroautophagy due to biallelic pathogenic variants in the ATG7 gene, encoding a core autophagy protein, leading to ataxia and neurological deficits. The aim of this PhD studentship is to understand the interplay between dysfunctional autophagy and human neural integrity using patient-derived induced pluripotent stem cell (iPSC) models, generating isogenic controls via CRISPR/Cas9-based genome editing. The successful student will use a suite of molecular, biochemical and microscopy-based techniques to study neuronal cell fate, function and survival, in addition to performing RNA-sequencing studies to further dissect and delineate the transcriptional landscape of ATG7-deficient neurons.

Sponsor: The Pathological Society

Name of supervisor(s): Professor Robert Taylor and Dr Monika OláhováTranslational and Clinical Research Institute, plus Professor Majlinda LakeBiosciences Institute

Funding Information

Tuition Fees, Stipend (standard RC UK rate) and consumables.

Eligibility Requirements

Applicants should possess – or expect to gain – a degree in a relevant subject at first or 2:1 level.

The award is available to Home applicants only.

Application Process

You must apply through the University’s online postgraduate application system. To do this please ‘Create a new account’.

Only mandatory fields need to be completed, including:

  • Programme code 8300F* in programme of study section
  • ‘PhD in the Faculty of Medical Sciences – Neuroscience’ as programme of study
  • Studentship code – TC022 – in the studentship/partnership reference field
  • A covering letter and CV. The covering letter must state the title of the studentship, the studentship reference code and state how your interests and experience relate to the project
  • Degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications.

* The online application system only allows one application with programme code 8300F. If applying for TWO or more projects using that code then you must email [email protected] with the following information:

Your application number (from the first submitted application)

The second studentship code and corresponding title

A two page covering letter for the second project.

For further details, please contact: Professor Rob Taylor ([email protected])

Application closing date: 3rd May 2021.

To apply for this PhD, please use the following application link: