Mechanistic studies on axonemal dynein transport to motile cilia

About the project

About the Project Motile cilia perform vital roles to maintain human health. Their motion is powered by macromolecular motors called axonemal dyneins. Large quantities of dynein motors need to be transported into cilia to generate their vital beating motion. Dynein motors are thought to be transported by the Intraflagellar Transport (IFT) system which comprises 22 distinct proteins that form train-like polymers to shuttle proteins in and out of cilia. Recent structural studies have revealed the overall molecular architecture of IFT trains that enter cilia. However, the molecular basis by which ciliary dyneins, particularly the force generating outer dynein arms (ODAs), attach to IFT trains remains poorly resolved. ODA transport requires packaging and inhibition by DNAAF9 (Shulin). Our most recent study suggests that Shulin not only inhibits ODAs but may also aid their attachment to the IFT system. This PhD project aims to build on our ongoing studies to elucidate the molecular mechanism of ODA motor attachment to IFT trains. The project will use an integrative cellular and structural biology approach combining biochemical reconstitutions, single-particle EM, protein structure modeling using AlphaFold and ultrastructure expansion microscopy (U-ExM).

Research areas