Seminar by Maxence Nachury

Speaker: Assistant Professor Maxence Nachury, Stanford University
Host: Associate Professor Lotte Bang Pedersen, Section for Cell Biology and Physiology

Abstract
First discovered in the early 1960’s, the primary cilium remained an “abortive structure with no function” for four decades. Fast forward to 2006 and the term “signaling antenna” is coined to describe primary cilia. This 180-degree shift in perception was fueled by two major advances: First, the ciliary hypothesis of polycystic kidney disease spread to the recognition of ciliary dysfunction as the pathological basis for the ciliopathies, a broad class of disorders characterized by obesity, cystic kidneys, retinal degeneration, skeletal malformations and brain anomalies. Second, Hedgehog signaling, a major developmental signaling pathway responsible for patterning the neural tube was shown to require cilia for its signal transduction. The cilium has now emerged as a vessel that transforms signaling inputs into processed information for the rest of the cell by dynamically concentrating signaling molecules within a specialized physicochemical environment.

Motivated by the tremendous importance of cilia in human health and disease and in signal transduction, our work aims to understand the basic principles of trafficking into and out of cilia and how the ciliary dynamics of signaling molecules affect signaling outputs. Historically, our lab pioneered the use of biochemical purifications of ciliopathy proteins to discover the BBSome, a protein complex with structural similarities to the coat complexes COPI, COPII and clathrin. In subsequent years, we developed single-molecule tracking, photokinetic assays and in vitro reconstitution to mechanistically dissect BBSome-mediated transport. Most recently, we leveraged nascent advances in proximity labeling to catalogue the protein content of cilia and profile alterations in the ciliary proteome that arise from ciliopathy mutations.  Our combined expertise in proteomics, biochemistry and imaging places us in a unique position to answer the central questions in ciliary biology.