R230136 – PhD Studentship (3 years) Brain on “FIRE” – investigating the role of microglia in epilepsy

Aston University


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College of Health & Life Sciences – Studentships
Location: 
Aston University Main Campus
Basis: 
Full Time
Closing Date:  23.59 hours BST on Monday 31 July 2023
Reference:  R230136
Release Date:  Monday 05 June 2023

PhD Studentship (3 years) Brain on “FIRE” – investigating the role of microglia in epilepsy

Department: College of Health and Life Sciences

Contract Type: Fixed Term

Basis: Full Time

Closing Date: 31st July 2023 [11.59pm GMT]

Supervisory Team: Supervisory team: Dr Sukhvir Wright, PI (BCH and Aston); Professor Gavin Woodhall, Associate Supervisor (Aston); Dr Clare Pridans, External Supervisor (University of Edinburgh); Dr Manoj Upadhya, Associate Supervisor (Aston)

Project Reference: HLS_Wright_Woodhall

Applications are invited for a three-year Postgraduate studentship, supported by Aston University’s Institute of Health and Neuroscience and Birmingham City Hospital, to be undertaken at Aston University. 

The position is available to start in October 2023.

Financial Support

This studentship includes a fee bursary to cover the Home fees rate, plus a maintenance allowance of £18,622 in 2023/4. This application is only available to Home students.

Background to the Project 

Immune cells are increasingly recognised as significant contributors to developing epilepsy and are implicated in up to 40% of the most devastating epilepsy syndromes1. Drugs that target the immune system can be beneficial in some of these patients with severe and difficult-to-treat epilepsy, however, they are not specific and affect the whole immune system leading to harmful side-effects2. Microglia, the resident immune cells in the brain, are primarily involved in the first and fast immune and inflammatory responses in the brain (i.e., the innate immune response). They are integral to maintaining brain function by removal of dying and non-functional neurons, synaptic pruning, and support of synaptogenesis3-5. Recent evidence points to microglia having critical roles in modulating neuronal activity6. Given their essential set of roles and responsibilities in the brain, it is not surprising that microglial dysfunction has been strongly implicated in the pathogenesis of neurological diseases including epilepsy7 In this PhD project we will generate disease models of difficult-to-treat epilepsy that genetically lack microglia and assess the impact on the underlying pathology, immunology, brain cell networks and signalling (electrophysiology). This work will build on existing work within the field of epilepsy in our laboratories.8,9 The successful candidate will benefit from learning established techniques of in vivo and in vitro electrophysiology, and immunohistochemistry to create the novel models proposed in this study. Establishing the role of microglia in the disruption of the normal crosstalk between the immune system and the brain in epileptogenesis will provide a specific therapeutic strategy that would treat and even prevent epilepsy, one of the most common neurological disorders. This ambitious and novel project will provide the PhD student with a team comprised of experts in cutting-edge immunology and neuroscience research combined with the clinical background to enable direct translation of findings to the clinic.

References: 1 Gaspard, N., et al. New-onset refractory status epilepticus: Etiology, clinical features, and outcome. Neurology 85, 1604-1613 (2015). 2 Dale, R. C., et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 83, 142-150 (2014). 3 Paolicelli, R. C., et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456-1458 (2011). 4 Schafer, D. P., et al. The “quad-partite” synapse: microglia-synapse interactions in the developing and mature CNS. Glia 61, 24-36 (2013). 5 Schafer, D. P., et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691-705 (2012).6 Badimon, A., et al. Negative feedback control of neuronal activity by microglia. Nature 586, 417-423 (2020). 7 Wu, W., et al. Microglial depletion aggravates the severity of acute and chronic seizures in mice. Brain Behav Immun 89, 245-255 (2020). 8 Modebadze, T., et al. A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat. PLoS One 11, e0147265 (2016). 9 Wright SK, et al. Multimodal electrophysiological analyses reveal that reduced synaptic excitatory neurotransmission underlies seizures in a model of NMDAR antibody-mediated encephalitis. Commun Biol. 2021 Sep 20;4(1):1106. doi: 10.1038/s42003-021-02635-8

Person Specification

The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in clinical medicine.  Preferred skill requirements include knowledge/experience of paediatric epilepsy.

Contact information

For formal enquiries about this project contact Sukhvir Wright by email at [email protected]

Submitting an application

As part of the application, you will need to supply:

  • A copy of your current CV
  • Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English
  • A research proposal statement*
  • A personal statement
  • Two academic references
  • Proof of your English Language proficiency

Details of how to submit your application, and the necessary supporting documents can be found here .  

Please select “Research Health Sciences” from the application form options.

*The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.

Please include the supervisor’s name, project title and project reference in your Personal Statement.

If you require further information about the application process please contact the Postgraduate Admissions team at [email protected]  

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