Defining the role of retromer in endosomal sorting in health and disease

Retromer, a highly conserved protein complex, is a master regulator of endosomal sorting, with defects in its function increasingly being linked to human disease. The observation of lower levels of retromer expression in the brains of Alzheimer's and Parkinson's disease patients, and the segregation of mutations in retromer and retromer-associated pathway components with Parkinson's disease, have further focused attention on this complex, and, more broadly, on the endocytic network's role in neuroprotection. However, little is known about how retromer works. During his award, Professor Cullen aims to define the inner workings of this machine, reveal fundamental information on cargo-sorting events conserved across eukaryotic phylogeny, and provide an insight into retromer's many roles in development and cell and organism physiology. Applying acquired knowledge to retromer's role in Parkinson's disease will provide unique insight into the cell biology of this disease.