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Structural Studies and Regulation of Intraflagellar Transport Complexes

Final Report Summary - CILITRANSPORT (Structural Studies and Regulation of Intraflagellar Transport Complexes)

In the ERC funded research project ‘CiliTransport’, the biological mechanisms by which eukaryotic cells form a cellular organelle known as the cilium were investigated. Cilia are the antenna of our cells and receive and process signals from the environment. Defects in the cilium can result in a number of human diseases known as ciliopathies. In this project, we examined how the cilium is constructed though an intracellualr transport process known as intraflagellar transport (IFT). To facilitate this work we reconstituted and purified the IFT machinery and studied its structure and function, which allowed us to elucidate how IFT proteins assemble to form large functional protein complexes. Several X-ray crystallographic structures were determined of IFT proteins and complexes to work out the architecture and mechanisms of IFT. Tubulin is a protein molecule that has the ability to polymerise and form the microtubule backbone of the cilium organelle. In a breakthrough study conducted within this ERC project, it was discovered how tubulin is recognized and transported into the cilium by the IFT81/74 complex in a study published in the journal ‘Science’ in 2013. Several other sub-projects within this ERC project looked at how the protein machinery for ciliary membrane protein import is composed, which is an important aspect of ciliary signaling. Additionally, investigated a number of patient ciliopathy mutations and characterized the mutant proteins with respect to structure, stability and function. In summary, the CiliTransport ERC project has significantly furthered our understanding of the process of IFT mediated cilium formation, a vital cellular process.