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Biological rhythms are key features of animal development; however, the underlying timers are not well understood. A novel biological oscillator, perhaps ancestrally related to the human circadian clock, times the molting cycle in C. elegans. The molting timer consists of interconnected feedback loops among the nuclear hormone receptor NHR-23, the microRNA let-7 and LIN-42, the worm homolog of the human circadian clock protein PERIOD. However, other components of the timer are not known. I hypothesized that the BLMP-1 protein is a core component of the molting timer in C. elegans. The extent to which BLMP-1 times the molting cycle was determined by comparing the duration of larval stages in blmp-1 mutants to that of wild-type animals. I characterized the temporal expression profile of the blmp-1 gene using the blmp-1p::gfp reporter gene which I introduced to the animals through transfection. In order to determine if NHR-23 activates blmp-1, I used the reporter gene to observe blmp-1 expression in stage-specific knockdowns of nhr-23. I found that blmp-1 mutants reach adulthood earlier relative to wild type animals, when both are released from starvation at the same time. Additionally, lower fluorescence intensity of blmp-1p::gfp is observed in nhr-23 mutants than in control animals, signifying that blmp-1 levels are lower in the absence of NHR-23. A deeper understanding of the molting timer can lead to insights in the biological clocks pertinent to humans which can be applied both to the circadian rhythm and to aging.

Assessing the Role of the Transcriptional Repressor BLMP-1 in the Molting Timer of C. elegans [University of California, Los Angeles]