Congratulations to Robert Hindges for receiving a Research Grant from the Leverhulme Trust, which will allow him to purse a three-year project entitled “Defining the molecular diversity of specific synaptic interactions”
A fundamental issue in neuroscience is to understand how our nervous system achieves the exquisite specificity of connections between the billions of neurons in order to guarantee the appropriate brain functionality. When neurons connect to each other and form synapses, they rely on molecular interactions at their membrane surfaces, for example through so-called ‘synaptic adhesion molecules’. These are crucial for cell-cell recognition and the formation of specific contacts. However, the overall number for such molecules found in the genome cannot easily account for the vast diversity of all connections in the nervous system and therefore another level of complexity must exist to expand the range of molecular interactions. One possibility is through the formation of complexes made from different molecules to generate a molecular combinatory code. The detection of such protein interactions has been predominantly done through in vitro imaging or through biochemical assays.
In this new project, the Hindges lab will use state-of the-art approaches to identify in detail protein complexes that are formed at synapses and characterize them directly in the brain of a living organism in real time. This will be achieved through the combination of genome-editing technology to label different synaptic proteins in certain neurons and then applying advanced live imaging methods, developed by Maddy Parsons from the Randall Division of Cell and Molecular Biophysics at King’s, collaborator on the project. Many neurodevelopmental disorders are linked to mutations in synaptic adhesion molecules and their interactions and, as such, the results from this study should therefore give crucial insights on how different protein interactions change synaptic specificity in the context of both the healthy and the diseased brain.
“I am looking forward to start this project as it combines the different expertise of Maddy Parsons’ group and ours to generate exciting new insight on how specific synapses are formed. We are grateful to the Leverhulme Trust for giving us the opportunity to carry out such unique research.”
Robert Hindges, Reader in Developmental Neurobiology