Cilia extend from every cell and function as a cellular antenna. They receive signals from outside the transmit the signal within. The causative gene mutations for disorders of the cilia suggest that they generally arise through problems in cilia-specific cargo trafficking. Yet, we do not understand how this process works. To address cargo delivery and retrieval at the cilia in health and disease, this project will explore how molecular machines at the cilia cooperate to regulate the logistics of cargo delivery to the cilia. We will use state-of-the-art automation and microscopy technologies based in the School of Life Sciences. We will combine this microscopy and the power of high-throughput methods with our expertise in protein biochemistry including homemade nanobodies. This cell biology approach will be combined with a bottom-up, protein biochemistry reconstitution of key steps in cargo delivery to cilia. The outcome of this project will be a foundational model for how cargo logistics are regulated at the cilia. This model will provide the information necessary to further compounds for addressing ciliopathies to provide better medical outcomes.
This project will enable student training at the interface of medical and basic science. Our lab takes multidisciplinary approaches at its heart and our aim in PhD training is to provide a fundamental expertise from which strong careers in academics and industry are possible.