Seth Grant

Seth Grant is Professor of Molecular Neuroscience at The University of Edinburgh’s Centre for Neuroregeneration and Centre for Clinical Brain Sciences.

Our research focuses on key proteins in the brain that are critical for austism spectrum disorder (ASD) as they are targets for FMRP and are mutated in other genetic forms of ASD. My lab specializes in genetic and proteomic approaches and we are currently developing microscopy to map synaptomes in mice and humans, which are being applied to ASD models.

The human brain has approximately 100 billion neurons that communicate with each other through 100 trillion synapses. Indeed, there are about 1000 times more synapses in the human brain than there are stars in the Milky Way! This photo shows the synapses in a small region of mouse brain labeled with fluorescent probes. Given this level of complexity, it is not surprising that even small changes at these synapses can dramatically affect the way the brain functions. This panel shows the synapses in about 1/3 of a millimeter of brain tissue.

The main goal of my laboratory is to understand molecular components in a specific subcellular structure of nerve cells called synapses. Every nerve cell has thousands of synapses and these are the connections that make up the brain’s circuits. My research has systematically identified the protein components of synapses, which provide a foundation for a wide range of basic and disease studies.

My work has demonstrated how neurotransmitter receptors, intracellular proteins and other molecules are assembled into ‘supercomplexes’, called MASCs, which are molecular machines distributed throughout the brain. Genetic studies in mice have demonstrated these proteins and supercomplexes are responsible for the organisation of the behavioural repertoire including instinctive and learned behaviours.

The proteomic studies also enabled the first studies of synapse evolution and identified the protosynapse origin of the brain in ancient unicellular organisms and the expansion in synapse complexity that arose in vertebrates with genome evolution.

Most importantly, these fundamental molecular studies have led to the discovery that more than 130 brain diseases involved the postsynaptic proteins, including common disorders such as schizophrenia, intellectual disability and autism spectrum disorders arise in postsynaptic proteins. These findings and approaches have underpinned the new field called ‘synaptopathy’ — the pathology of the synapse.


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