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CiliaCircuits SIGNED

Molecular Principles of Mammalian Axonemal Dynein Assembly

Total Cost €

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EC-Contrib. €

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Partnership

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 CiliaCircuits project word cloud

Explore the words cloud of the CiliaCircuits project. It provides you a very rough idea of what is the project "CiliaCircuits" about.

construction    vision    disease    mechanisms    cellular    allocation    ciliacircuits    prevent    responsive    feedback    enough    toxic    poses    machinery    biology    regulation    cure    complexes    induction    tiny    flow    proposes    assembly    molecules    candidate    differentiation    exist    tells    date    movement    sizeable    projections    health    nature    microtubule    proteome    motors    dynamic    axonemal    aggregation    therapeutics    human    primary    coordinated    fluid    expenditure    assembled    genetics    additional    macromolecular    transcriptional    space    elucidate    powered    hundreds    genes    ciliogenesis    motile    translational    pose    millions    translation    trafficked    risk    surplus    global    dyneins    cilia    cell    motility    dyskinesia    question    subsequent    cells    molecular    exists    correct    regulating    pcd    understand    ciliary    logic    time    almost    action    create    circuitry    implicated    adaptive    dynein    dynamics    cytoplasm    fraction    crowded    stoichiometry    super    subunits    underlying    resolution    specialized    code    unexplored    streamlined    extreme    futile   

Project "CiliaCircuits" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF EDINBURGH 

Organization address
address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL
website: www.ed.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 1˙965˙459 €
 EC max contribution 1˙965˙459 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-04-01   to  2025-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) coordinator 1˙965˙459.00

Map

 Project objective

Motile cilia are tiny microtubule-based projections which create fluid flow and are essential to human health. Cilia movement is powered by coordinated action of complex macromolecular motors, the axonemal dyneins. During differentiation, as cells produce hundreds of motile cilia, millions of dynein subunits must be pre-assembled in the cytoplasm into very large complexes in the correct stoichiometry which are then trafficked into growing cilia. This poses a sizeable challenge for the cell in terms of allocation of a significant fraction of the global translational machinery for streamlined assembly of dyneins within a crowded cellular space.

The key question remains: How does the cell know how much is enough? This is an extreme example of a common problem in cell biology. Responsive and adaptive mechanisms must exist to prevent futile expenditure of cellular resources in making a surplus of large molecules like dyneins that may also pose a risk of toxic aggregation. While a well-defined transcriptional code for induction of cilia motility genes exists, the translational dynamics and subsequent feedback circuitry coordinating dynein pre-assembly with ciliogenesis remain unexplored.

The molecular logic underlying the construction of motile cilia assembly are still not fully understood. The ambitious nature of CiliaCircuits proposes to use super-resolution and systems approaches to elucidate key mechanisms regulating this process in health and disease.

Human genetics tells us that making cilia motile is a complex process. To date, almost 40 genes have been implicated in primary ciliary dyskinesia (PCD), the disease of motile cilia, for which there is no cure. The long-term vision is to understand this dynamic control operating over a specialized proteome in time and space in order to develop effective PCD therapeutics and identify additional candidate genes involved in this translation regulation.

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The information about "CILIACIRCUITS" are provided by the European Opendata Portal: CORDIS opendata.

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