Modelling monogenic epilepsy in human brain slice cultures (Neuroscience)

About the Project

Approximately 1 in 2000 children develop epilepsy before three years of age from a monogenic cause; of these, a third will continue to have seizures into adulthood. The pathological mechanisms often remain obscure, even when causative mutations have been identified, partly because pathology may start in utero, which makes its study extremely difficult. To address these challenges, and study the critical prenatal developmental mechanisms, we have established a novel experimental approach using intact human cortical network, through the Human Developmental Biology Resource (HDBR), to study the developmental consequences of altered prenatal gene expression. We have created living organotypic cultures of the developing human neocortex, in which we can manipulate expression levels of specific genes of interest. We may then examine synaptic development and neuronal network function, using state-of-the-art imaging and electrophysiological techniques. We will also investigate downstream changes in gene expression to identify potential compensatory or pathophysiology modifications. This approach can transform the clinical management of neurodevelopmental conditions in two important ways: by providing a means of validating the pathological consequences of newly identified mutations, and creating a framework for investing gene-therapy to reverse any phenotypic changes.
How to Apply:

Applications should be made by emailing epilepsy.research@newcastle.ac.uk

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT http://www.cando.ac.uk/eruk-phd/ . Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Application Form (as a Word document) to epilepsy.research@newcastle.ac.uk A blank copy of this form can be found at: http://www.cando.ac.uk/eruk-phd/

Informal enquiries may be made to epilepsy.research@newcastle.ac.uk. The closing date for applications is 31st March 2022 at 5.00pm (UK time).
Funding Notes
PhD studentships are funded by Epilepsy Research UK (ERUK) for 3 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant and stipend (£15,609, 2021/22 rate). Applications are welcomed from students in all countries, although students from outside the UK will be required to pay full international fees. International students may be eligible for financial support to cover some or all of these fees.
References
McLeod et al (2021) bioRxiv 2021.09.22.461333; doi: https://doi.org/10.1101/2021.09.22.461333


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