PROJECT SUMMARY
Both inputs to the brain and outputs from the brain occur over a broad range of timescales and
in many cases repeat rhythmically. Rhythmic changes in gene expression have been studied
in the brain only in the context of circadian rhythms. Additionally, shorter-than-a-day (ultradian)
rhythms have been sparsely reported and it is unknown how these rhythms originate,
particularly at the molecular level and whether they interact and/or share part of the
timekeeping machinery utilized by the circadian clock. Understanding how these rhythms are
generated and maintained will illuminate new aspects of brain gene expression and physiology
and open unexplored areas of research.
In an effort to reveal RNA oscillations at different timescales in the fly brain, we profiled fly brains
by RNAseq every two hours for three days. By analyzing these data, we identified dozens of
RNAs oscillating with 6-, 12-, and 24-hour rhythms in the brain. Interestingly, enrichment
analysis shows that more than half of these genes are highly expressed in the glia, suggesting
this cell type has oscillators operating at different timescales. The importance and novelty
of these results are two-fold: a. they demonstrate, for the first time, the presence of ultradian
RNA oscillations in the fly brain; b. suggest the existence of oscillators operating at
different timescales (circadian and ultradian) in the glial cells. In this context, the present
proposal aims to comprehensively identify the mechanisms responsible for ultradian
rhythmic gene expression in the glial cells within the fly brain. Our work will shed light on
new mechanisms of ultradian expression in flies for the first time. In addition, we will identify
and characterize new timekeeping or timer-like mechanisms operating in glial cells that also
have a circadian clock. Last, our work will provide new information and lead to developing tools
to perturb and investigate these rhythms in the future.
In sum, we are convinced that this project will uncover new modes of timed regulation of
transcription and physiology within the brain, which might be of vast importance beyond
Drosophila and uncover potential connections between ultradian and circadian oscillators
within these cells. This pioneering study will set the stage for further studying the role of
oscillations in the glia, a key cell type in the brain, as well as to understand the mechanism and
role of ultradian rhythms in general. As circadian rhythms have been linked to numerous diseases
including depression and sleep disorders, the present proposal has obvious implications for
human health.