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Contenuto archiviato il 2024-05-30

Towards a systemic view of the circadian clock: Integration of miRNAs into the molecular, cellular and neural circadian networks

Final Report Summary - MIRNACLOCKNETWORKS (Towards a systemic view of the circadian clock: Integration of miRNAs into the molecular, cellular and neural circadian networks.)

miRNA clock networks is a multidisciplinary initiative to understand the complexity of the circadian system in Drosophila. To achieve our objective we have used the most advanced molecular, neural, physiological, imaging and computational techniques. These include the adaptation of molecular technologies for their use in fly heads as well as the development of new genomic and imaging approaches. Circadian clocks time physiology and behavioural processes to 24 hours rhythms. The main objective of the present project is to try to understand how these clocks achieve robustness in particular in face of environmental perturbation. In the present project we exploit complementary and cutting-edge approaches to provide an integrative and comprehensive view of the circadian timekeeping system. For doing so, we use Drosophila, a genetically tractable animal system.
During the tenure of the ERC project we have: 1) determined that post-transcriptional control of the master regulator Clk denoises circadian transcription in time and space; 2) developed an ex vivo brain culture system in combination with circadian fluorescent reporters, which allow us to follow circadian transcription continuously from cultured brains; 3) developed a high-throughput annotation and quantification RNA-sequencing based approach; 4) performed a global genome-wide assessment of transcriptional and post-transcriptional control of the circadian system in normal conditions and under temperature perturbation and 5) performed a double interaction screening for revealing functional inter-relationships between different components and pathways of the timekeeping machinery.
All these experiments allowed us to examine properties of the circadian as a whole (from the single cell to the neuronal network level) and to understand key properties of the compensatory responses behind the robustness of the circadian system.