My laboratory at the UCL Institute of Neurology now combines automated behavioural monitoring with advanced Drosophila genetics, molecular biology, confocal and super-resolution imaging to investigate how neuronal activity and synaptic function is regulated at the genetic level and to use this information to more fully understand the molecular basis of human neurological diseases.
Role in the Synaptopathies Initiative
We have developed a ‘clinic to fly’ pipeline for characterising novel mutations that affect neuronal excitability and development. We are using data derived from exome sequencing of patients with a variety of paroxysmal disorders as a guide to search for evolutionary conserved loci that play important roles in both the human and fly nervous systems.
Drosophila represents an excellent model for understanding gene function due to its astonishingly diverse genetic toolkit. Using techniques such as ends-out homologous recombination, P-element mutagenesis and transgenic RNAi we are generating knock-in, knock-out and knock-down models of a range of neurological diseases associated with genes whose roles in nervous system function are poorly understood.
Through this strategy we hope to complement human disease genetics with in vivo functional data in order to elucidate the cellular and molecular basis of paraxoysmal disorders.