Biological clocks and timers in development
The development of an animal requires proper temporal synchronization of diverse events, facilitated by developmental clocks. How such clocks function is only beginning to emerge. What are their properties? What are the components that make them run, and how are they wired? To solve these questions, we investigate developmental timing in the roundworm C. elegans, where we can exploit our recent discovery that thousands of genes oscillate in expression during larval development. Such extensive and robust molecular clock output, combined with powerful tools for genetic manipulation and screening, makes C. elegans uniquely suited for dissecting the underlying clock mechanism. We combine high-throughput single animal-based methods including quantitative time-lapse imaging with genomics, genetic and computational approaches to record and alter oscillations and developmental timing. Thus, we aim to establish a mechanistic and quantitative model of the clock.
Although oscillator-based developmental clocks are crucial to control execution of repetitive events such as the formation of vertebrae in mammals, distinct mechanisms time linear progression. For instance, transition from juvenile (larval) to adult fates in C. elegans relies on a regulatory cascade, where an RNA-binding protein, LIN28, represses a miRNA, let-7, which in turn represses another RNA-binding protein, LIN41/TRIM71. The functions of these factors appear conserved in mammals where they regulate stem cell fates and, possibly, the onset of puberty. Working with C. elegans and mammalian cells, we aim to obtain a full mechanistic understanding of this pathway and its components to understand how control of 'linear time' is achieved and integrated with clock-controlled processes.
FMI report pages for Helge Grosshans