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Research Portfolio

GRANT TITLE:

Investigating chromatin misfolding as a pathogenic mechanism in neurodevelopmental disorders

GRANT TYPE:

Epilepsy Research Institute & MRC CLINICAL RESEARCH TRAINING FELLOWSHIP

grant amount:

£270,458

lead investigator:

Dr Oliver Davis

Co-Investigators:

-Dr Srinjan Basu
-Dr Andras Lakatos

institution:

University College London

Background

In epilepsy, electrical activity in the brain is imbalanced and seizures can occur when there is a sudden burst of activity. There are some cells in the brain that stimulate electrical activity whilst other cells inhibit electrical activity. People with epilepsy have too many of these stimulating cells and not enough inhibiting cells.

The DNA in our cells must be folded and stored correctly to give instructions to the cell and allow it to function properly. If not folded and stored properly, the DNA may not be able to instruct the cell about whether it should be stimulating or inhibiting electrical activity. This could be one of the reasons why people with epilepsy have an imbalance of these stimulating and inhibiting cells.

"The findings of this study could have strong scientific and medical implications for epilepsy. We will provide some much-needed insight into how genes with DNA folding functions control how our brains develop. This will be important medically, as it opens up the possibility that DNA misfolding is a mechanism for how some forms of epilepsy arise (particularly those that are hard to treat and co-occur with other neurological conditions). Critically, this will provide new targets for scientists to design diagnostic tests or drugs for treatments, which could really help to improve the care of patients with hard-to-treat forms of epilepsy.

The Study

This study will investigate two genes that control DNA folding (called FOXG1 and CHD2). Using cells in a dish to model a brain, the team will investigate  what impact turning off these genes has on DNA folding and if this influences the number of cells that inhibit electrical activity.

Significance

This study will shed light on how genes that control DNA folding contribute to the balance of electrical activity in our brains. Future research could build on this to find new treatments that target these genes.