Circadian clocks organize cellular, physiological, and behavioral timing in 24-hour cycles. Understanding how circadian rhythms are generated, maintained, and adapted to changing conditions is key, as several diseases such as cancer and depression are associated with misalignment of the circadian clock with the environment. The current model postulates that circadian oscillators keep time by complex transcriptional and post-transcriptional feedback loops. Circadian clocks are remarkably robust: they are able to keep time without timing cues and are resilient to large variations in environmental conditions. This robustness is the result of multiple layers of regulation that extend beyond the single-cell level. Circadian clocks are also exceptionally plastic as they can quickly and specifically adjust to specific environmental cues. This plasticity is the result of the existence of very efficient input pathways that convey the external signals into the core oscillator machinery.
Our lab is interested in determining how molecular and neural circadian components regulate each other and generate a system that is both robust and plastic. For doing this, we study the circadian clock from a systemic point of view, including studies at the molecular and neural levels. We showed that miRNAs have a key role in providing robustness to the circadian system both during development and in adults. Moreover, we also showed that the neural and molecular circadian systems compensate and interact with each other.
In this context, the most important question looking forward are:
- What is the contribution of non-coding RNAs (small and large) to the robustness of the circadian system? What is their mechanisms of action?
- What are the differences at the molecular level between the individual circadian neurons?
- What are the general mechanism of the circadian clock to deal with genetic and/or environmental perturbations?
- What are the neural and molecular basis of temperature adaptation and compensation?