Towards a thorough mechanistic understanding of endosomal cargo sorting.

For over ten years my laboratory has been identifying the mechanistic basis by which proteins and lipids are sorted through a specific aspect of the human cell's intracellular membraneous maze, the endosomal network. We have studied a number of ancient, highly conserved protein complexes that act as molecular machines to orchestrate protein and lipid transport through this network. One of these is the retromer complex. Our research, and that of others, is defining retromer function and is revealing its importance in a variety of cellular processes that are vital for normal cell function. Furthermore, it has become apparent that defects in retromer underlie a variety of human diseases including age-related neurodegenerative diseases such as Parkinson disease and Alzheimer disease. With Wellcome funding we will address new fundamental questions arising from this research, thereby providing greater fundamental insight into retromer's many roles in normal physiology and its deregulation in pathophysiology.