First Non-Repeating Biological Clock Found in Worms
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- Christopher Hammell and colleagues at Cold Spring Harbor Laboratory identified proteins MYRF-1 and LIN-42 as the feedback circuit forming C. elegans' master developmental clock, publishing the work in PNAS (DOI: 10.1073/pnas.2606846123).
- MYRF-1 acts as the trigger that initiates each developmental stage and marks its completion, while LIN-42 regulates the intensity and duration of each gene-expression pulse, with the two proteins ensuring stages proceed in the correct order.
- Hammell described the mechanism as the first non-repeating biological clock of its kind — a ratchet that turns genes on and off multiple times but only progresses in one direction toward adulthood.
- When researchers blocked MYRF-1, the entire developmental program broke down; Hammell said that 'without the right key for each stage, development hits a wall and can't progress.'
- The team combined traditional molecular biology, DNA and protein sequencing, and the AlphaFold AI tool to resolve the clock's mechanism, with CSHL Director of Research Leemor Joshua-Tor serving as co-author.
- The MYRF-1/LIN-42 circuit runs independently in every cell yet stays synchronized during normal development, raising an open question the team admits they have 'never thought deeply about': whether individual cellular clocks communicate with one another.
Why it matters: This is the first identified non-repeating biological clock, answering a long-standing question about how organisms schedule sequential, once-per-lifetime developmental events. The MYRF-1/LIN-42 mechanism gives researchers a concrete molecular entry point into human conditions where development stalls or misfires.
