ProfessorPhillip Robinson

His research program focuses on understanding the molecular mechanisms of synaptic transmission in the nervous system. His work brings together cell signalling with protein chemistry and medicinal chemistries to: a) understand the basic science of nerve communication and b) develop drugs to control diseases of nerve terminals like epilepsy. Nerve communication involves neurotransmitter release at contact points between nerves – synapses. It occurs from small storage vesicles, synaptic vesicles, which accumulate at synapses. They must be recycled locally or synaptic transmission stops, resulting in paralysis. The main focus is on proteins called the dynamins, which are self-assembling molecular machines acting in many intracellular functions. Dynamin can self-assemble as a helix at the neck of newly forming synaptic vesicles to cut it free into the cell a process called endocytosis. There are three dynamin genes: dynI (neuron specific), dynII (ubiquitously expressed) and dynIII (low levels in neurons and testes) and dynII mutations cause Charcot-Marie Tooth neurodegeneration, the muscle disease Centronuclear Myopathy and childhood leukaemia.

Phil and his team have made many discoveries about the molecular mechanisms of endocytosis at the synapse. His work revealed that synaptic vesicle endocytosis is a highly regulated process in neurons, triggered by protein dephosphorylation. He uses mass spectrometry for phosphoproteomics to identify all phosphosites in all endocytic proteins and to rank them by abundance and physiological relevance. By working together with the Medicinal Chemist, Adam McCluskey, at the University of Newcastle they have utilised the new knowledge to develop potential new drugs. This represents part of an overall strategy to develop dynamin and endocytosis inhibitors: a) as tools for medical researchers to solve significant biological problems, and b) as potential candidate therapeutics for human disease indications in which harnessing endocytosis pathways may alleviate disease symptoms for epilepsy, cancer, infectious diseases and chronic kidney disease.