MIRNACLOCKNETWORKS (260911)

  https://cordis.europa.eu/project/id/260911

  FP7 (2007-2013)

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

  ERC Starting Grant - Neurosciences and neural disorders (ERC-SG-LS5)

  proteomics  ·  computational intelligence

  2011-02-01 Start Date (YY-MM-DD)

  2016-01-31 End Date (YY-MM-DD)

  € 1,478,606 Total Cost

  Description

Circadian (24hs) rhythms in locomotor activity are one of the best-characterized behaviors at the molecular, cellular and neural levels. Despite that, our understanding of how these rhythms are generated is still limited. A major shortcoming of the current approaches in the field is that they depict the circadian clock as a mere addition of steps (and/or combination of parts). By doing so, the circadian oscillator is portrayed as a static rather than a dynamic system. We have recently shown for the first time that miRNA-mediated regulation plays a role in circadian timekeeping in Drosophila. In the present project we will exploit complementary and cutting-edge approaches that will provide an integrative and comprehensive view of the circadian timekeeping system. As we believe that miRNAs are key mediators of this integration, we will dissect their role in the circadian clock at the molecular, cellular and neural levels in Drosophila. At the molecular level, we will determine the mechanisms, and proteins that mediate the circadian regulation of miRNAs function. Moreover, by the use of high-throughput methodology we will assess and characterize the impact of translational regulation on both the circadian transcriptome and proteome. At the cellular level, we plan to determine how this type of regulation integrates with other circadian pathways and which specific pathways and proteins mediate this process. As a final goal of the proposed project we plan to generate a complete genetic interaction map of the known circadian regulators, which will integrate the different molecular and cellular events involved in timekeeping. This will be a key step towards the understanding of the circadian clock as a dynamic adjustable process. Last, but not least, we will study the role of miRNAs in the circadian neural network. For doing so we will set up an ex vivo approach (fly brain's culture) that will assess circadian parameters through fluorescent continuous live imaging.

  Complicit Organisations

1 Israeli organisation participates in MIRNACLOCKNETWORKS.