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Understanding mechanisms and functions of miRNA oscillations during development

Project description

Rhythmic gene expression during development

Emerging evidence indicates that the expression of certain genes during development is rhythmically controlled. However, the precise molecular mechanism remains elusive. In the nematode Caenorhabditis elegans nearly 2 700 genes exhibit oscillatory expression during the larva stage, including certain regulatory miRNA genes. The EU-funded miRhythm project will follow a multidisciplinary approach to delineate the function of specific oscillatory miRNAs in rhythmic gene expression. Results will shed light on the temporal orchestration of key developmental events such as cell proliferation and differentiation. Importantly, miRhythm will help us understand the mechanisms underlying biological timing.

Objective

Successful development of an organism relies on careful temporal orchestration of a large number of diverse events. Although processes such as cell proliferation, migration and differentiation are thus under precise temporal control, molecular mechanisms of the relevant biological timers have remained largely enigmatic. I propose to exploit the repetitive development and robust oscillatory gene expression of the nematode C. elegans to identify fundamental principles of temporal control of organismal development through rhythmic gene expression. High temporal reproducibility of developmental progression and genetic tractability are additional major assets of this novel experimental paradigm.
Previous work in my host-lab uncovered high-amplitude oscillatory expression of ~2700 genes peaking exactly once per larval stage, with an ~8-hr period. These oscillations appear to orchestrate periodic developmental events encompassing synthesis and shedding of the cuticle, cell proliferation and differentiation. A small set of regulatory miRNAs also exhibit oscillations with large amplitudes. This is surprising given that miRNAs are generally quite stable, and that the transcript level oscillations appear to be rely mostly on rhythmic transcription. Here, I propose to delineate the function of oscillatory miRNAs in rhythmic gene expression and development, and the mechanisms that render them sufficiently unstable to facilitate oscillation. Thus, through a combination of high-throughput developmental tracking, single-cell sequencing, bioinformatics, and biophysics approaches, I expect to uncover molecular mechanisms that control developmental timing and miRNA metabolism.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 203 149,44
Address
FABRIKSTRASSE 2
4056 BASEL
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 203 149,44
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