Unity and diversity of multiciliary function across scales

Motile cilia are found across most eukaryotes. These cellular appendages have conserved morphology yet have evolved to perform highly divergent functions in different organisms, e.g. swimming or gliding motility, fluid transport, or mucociliary clearance. Biochemistry and genetics have provided a ‘parts list’ of cilia along with structural blueprints from detailed electron microscopy studies. However, we have little mechanistic understanding of how ensembles of cilia cooperate in different contexts to achieve the desired function. With our interdisciplinary programme, we will investigate the biophysical principles of multiscale coordination of cilia motility by leveraging the power of model organisms, live imaging, and fully-integrated, empirically testable computational models. Our model species span several orders of magnitude in scale and complexity, from single cells to complex mammalian tissues, capturing diverse naturally-occurring ciliary configurations. By exploiting genotype-phenotype mappings across scales and model species, we will uncover key principles that underlie multiciliary function and pathophysiology. The ability to understand and predict how interactions between large numbers of components drive complex behaviours will provide key insight into the physics of ciliary systems. It will also catalyse new perspectives on our understanding of human motile ciliopathies and how multiple components are integrated to generate functional fluid flows.