Research in our lab aims to understand the molecular mechanisms and signaling pathways that control the distribution and dynamics of subcellular components, focusing on structure, function, molecular mechanism and regulation of the key biomolecular machines and multiprotein complexes that regulate cellular organisation. We also seek to apply that knowledge to develop novel chemical tools to manipulate these systems. We take a multi-disciplinary approach that combines advanced cell imaging with cell biology, biophysics and structural approaches to define the molecular basis of these dynamic processes.

Our first major contribution was to show, how a microtubule motor motor, in this case kinesin-1, recognises the some of the cargo that it carries (Science. 2013.19, 356-9). We have since gone onto show how cargo engagement can regulate the activity of the motor (PNAS. 2016. 113, 2418-23) and identifed new cargo recognition mechanism (eLife. 2018). An important focus us now in this area is to use this information to develop small molecules that can manipulate this mechanism and to understand whether such molecules may be of therapeutic use. Our proof-of-concept study describing the first such compound, kinesore, was recently published (PNAS. 2017. 114, 13738-13743).

In another research theme, we have studied how the spatial organisation of the lysosomal membrane compartment is regulated by metabolic state, and in doing so, implicated a tumour suppressor protein called Folliculin in controlling inter-organelle contacts between lysosomes and the Golgi apparatus (EMBO Reports. 2016. 17, 823-41). Our continuing work in this area is focusing on understanding how the architecture of the lysosomal membrane compartment is re-established after cell division.