Modelling monogenic epilepsy in human brain slice cultures (Neuroscience)

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 [Email Address Removed] with:

• a CV (including contact details of at least two academic (or other relevant) referees);
• A covering letter – clearly stating your first-choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s);
• copies of your relevant undergraduate degree transcripts and certificates;
• a copy of your passport (photo page).

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 [Email Address Removed]  A blank copy of this form can be found at: http://www.cando.ac.uk/eruk-phd/

Informal enquiries may be made to [Email Address Removed]. The closing date for applications is 31st March 2022 at 5.00pm (UK time).