Cilia perform essential functions in development, fertility, and health, and their dysfunction causes ciliopathies, ranging from developmental disorders to degenerative diseases, many of which affecting the brain. Assembly and functions of all cilia rely on intraflagellar transport (IFT), a bidirectional trafficking system powered by Kinesin-2 (anterograde) and Dynein-2 (retrograde), which associate with IFT-A and IFT-B complexes to form IFT trains.

Our lab showed that WDR-60 mediates Dynein-2 loading onto anterograde trains, enabling its transport all the way to the tip for IFT turnaround. We also showed that IFT-A is key for retrograde IFT. However, the mechanism that releases and activates Dynein-2 at the ciliary tip to initiate retrograde IFT remains unknown.

Interestingly, cilia with mutated ciliopathy-associated Kinase 1 (ICK) accumulate IFT subunits at the ciliary tip resembling retrograde defects. Furthermore, mutations in ICK, Dynein-2, or IFT-A cause ciliopathies with overlapping phenotypes.
In this context, the CiliarICK project will investigate the role of ICK in Dynein-2 activation and IFT turnaround.
Using C. elegans, advanced imaging, proteomics, and genetics, we aim to:

1. Dissect the molecular interplay between ICK, IFT-A, and Dynein-2;
2. Identify novel DYF-5/ICK targets regulating IFT;
3. Define their functional roles in retrograde transport and ciliary signaling.

These studies will reveal how ICK fine-tunes Dynein-2 activity and provide key insights into the molecular basis of retrograde IFT-associated ciliopathies.