Professor Sir Adrian Bird jointly awarded 2020 Brain Prize

Wednesday, 29 April, 2020

Many, many congratulations to Professor Sir Adrian Bird (Buchanan Professor of Genetics, Wellcome Centre for Cell Biology, and Simons Initiative for the Developing Brain) on being jointly awarded The Brain Prize for 2020 with Professor Huda Zohgbi (Professor of Paediatrics, Human and Molecular Genetics, and of Neurology and Neuroscience, Baylor College of Medicine in Texas).

Affectionately known as the ‘Nobel of Neuroscience’ this is one the most prestigious prizes a neuroscientist can be awarded. Established by the Danish-based Lundbeck Foundation, it is awarded each year to one or more brain researchers who have had a ground-breaking impact on brain research.

Selected from over 100 nominations, Huda and Adrian have been awarded The Brain Prize for their fundamental, pioneering work on a disorder affecting children, called Rett Syndrome.

Rett syndrome, first described in Vienna in 1966, is a devastating genetic disorder that typically becomes apparent after 6 to 18 months of age in baby girls. Symptoms include problems with coordination and repetitive movements, and later with language development. Often there is slower growth, problems with walking and a smaller head size. Additional complications can include seizures and sleeping problems. Its prevalence is about 1 in 8000 females.

Adrian Bird and Huda Zohgbi identified alterations in a protein called MeCP2 as the cause of this brain disorder.  Adrian discovered that MeCP2 interacted with methylated DNA as well as a gene silencing complex, which results in the gene silencing machinery being delivered to methylated sites in the genome. Huda’s work with female Rett Syndrome patients revealed that they had a mutation in MeCP2.

Because the MeCP2 gene is on the X chromosome, girls carrying a Rett mutation have brains that are mosaic for the mutation, meaning some cells express mutant MeCP2 protein while others express normal protein. By contrast, in males, all brain cells are affected, and the condition is lethal before birth.

The generation of a knock-out mouse model by Adrian’s lab (where the MeCP2 gene is removed) and a mouse model bearing the human mutation in MeCP2 created by Huda’s lab establishing that MeCP2-deficiency in the brain is responsible for the human condition. Surprisingly whilst a lack of MeCP2 is problematic, it turns out that having too much MeCP2 is also damaging.

Most excitingly, Adrian’s lab also established that, in mouse models, the condition could be reversed by triggering activation of quiescent MeCP2 after development, changing the notion that neurodevelopmental disorders can’t be altered once established.  For children and families around the world, it also raises the possibility that Rett Syndrome may be treatable in humans. Clinical trials are now imminent.

Professor Sir Adrian Bird said "I am truly honoured to be awarded the Brain Prize. I have been fortunate to work with outstanding people over the years, and this recognition from the Lundbeck Foundation is also a credit to them. Like so many discoveries that have turned out to be biomedically important, the work we began in the 1990s started out as blue-skies research with no obvious practical benefit. I am grateful for all the generous support I’ve received from the University, the Wellcome Trust and the Rett Syndrome Research Trust since those early days."

This is the second time the Brain Prize – now in its tenth year – has been awarded to an Edinburgh Neuroscience researcher. In 2016 Professor Richard Morris was one of three academics recognised for their work on the mechanisms of memory.

Adrian is also a founding member and Director of the Simons Initiative for the Developing Brain (SIDB).