Building a minimal contractile machineGroup Leader Page
Cilia are found on all cells and have functions ranging from receiving signals to moving mucus out of the lungs. At their feet are basal bodies and below these are long striated filaments known as rootlets. This cytoskeletal filament is hardly mentioned in textbooks and little is known about its function and yet mutations in them cause ciliopathies (a class of genetic diseases related to loss of cilia function). In some algae the rootlets can act as mini-muscles that contract and pull the nucleus towards the base of the cilia. It is not known if any human rootlets have the same function or what the role of this contraction is.
This PhD project will involve reconstitution of rootlets from its known components. The structure of these reconstituted rootlets will be solved by cryoEM with the goal of understanding how a filament can contract with enough force to move the cell’s largest organelle. The project will provide training in biochemistry and structural biology. It will provide the opportunity to improve our understanding of one of the most enigmatic structures in the cell.
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Vlijm R, et al. (2018) STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles. Proc Natl Acad Sci U S A. 115:E2246-E2253.
Mali GR, Ali FA, Lau CK, Begum F, Boulanger J, Howe JD, Chen ZA, Rappsilber J, Skehel M, Carter AP‡ (2021) Shulin packages axonemal outer dynein arms for ciliary targeting. Science. 371:910-916.