Objective
Cilia are microtubule-based protrusions of the plasma membrane found on many eukaryotic cells, including most cell types of the human body. Whereas the functions of motile cilia were immediately obvious, the role of the immotile or so-called primary cilia remained largely unrecognized for many decades. Once referred to as aberrant solitary cilia with no obvious function, these ancient structures now hold the promise of revealing no less than the secrets of multicellularity and development. Even though the importance of primary cilia is now evident, molecular mechanisms underlying their assembly and function are far from being understood. The construction and maintenance of cilia relies on an ancient, universally conserved machinery termed IntraFlagellar Transport (IFT). IFT requires a multi-subunit, non-membranous protein complex assembled from more than 20 distinct subunits. At the heart of IFT are the microtubule-associated motors, -kinesin and dynein-, that continuously ferry cargo in a bi-directional fashion needed for ciliary assembly and function. To pave the way towards a molecular understanding of this fascinating organelle, we propose to employ a bottom-up approach in which we stepwise reconstitute the IFT complex from recombinantly expressed subunits of the so far best understood primary cilium from C.elegans. The structural integrity and stability of the IFT complex will be characterized using multifaceted approaches such as chemical crosslinking or thermophoresis. To mechanistically dissect the kinesin-dependent transport in vitro, we will make use of enzymatic bulk and single-molecule assays. Collectively, these results will provide a quantitative understanding of the assembly and kinesin-dependent motility of the IFT machinery. Given that cells mobilize ~600 components to build their cilia, this experimental platform will significantly streamline future efforts to identify novel cargoes and the effects of putative regulators of the IFT machinery.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2013-StG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
80333 Muenchen
Germany
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.