"[In C. elegans] researchers uncovered key principles of cell death and RNA interference [that] paved the way for new therapies and technologies. These breakthroughs were made not because they were sought by design, but because a few scientists, supported by public grants, followed their curiosity"

Fabulous @katb92.bsky.social was the lead on our side!

This invites speculations about the evolution of circadian vs. developmental clocks and the features that make the PER/LIN-42:CK1/KIN-20 module so central to different timing mechanisms – as discussed in the accompanying News & Views article @embojournal.org doi.org/10.1038/s443... . 8/n

Intriguingly, this tango also appears to happen in circadian clocks: while CK1 licenses PER for degradation, PER also regulates CK1 activity and its targeting of the CLOCK protein in the nucleus. 7/n

Indeed, KIN-20 exhibits dynamic localization to the nucleus – dependent on LIN-42 binding. We speculate that this may provide KIN-20 to access to additional substrates. 6/n

Animals lacking CK1/KIN-20 or its enzymatic activity are highly arrhythmic – in fact much more so than animals only lacking the LIN-42_CK1BD. This made us wonder whether the key function of the complex is regulation of KIN-20 by LIN-42, rather than the other way around. 5/n

LIN-42 co-immunoprecipitates KIN-20 – an orthologue of Casein Kinase 1delta/epsilon that also occurs in a complex with PER in mammals. The LT/SYQ region forms a CK1-binding domain (CK1BD) that also regulates CK1 activity. CK1 phosphorylates LIN-42. 4/n

Its most conserved feature are the PAS (PER/ARNT/SIM) domains – but we find them to be dispensable for rhythmic molting. Instead, a less conserved region previously termed LT/SYQ for an amino acid signature is required. 3/n

The C. elegans LIN-42 protein is orthologous to fly/mammalian PERIOD – but during development, oscillates with a 7-hr rather than a 24-hr period. It affects temporal cell identity and promotes rhythmic molting – but how, was unclear 2/n

Thanks you, Xantha!

Absolute fun project with lead authors Dimos Gaidatzis (@fmiscience.bsky.social Comp Bio), Maike Graf-Landua and @smethot.bsky.social - and many other wonderful collaborators @labgrosshans.bsky.social ky.social and @fmiscience.bsky.social. Thanks to @snsf.ch and @erc.europa.eu for funding! n/n