Cilia are hair-like organelles that extend from the surface of virtually all polarized cell types of the human body. They are crucial for various motile and sensory functions during development, morphogenesis and homeostasis. Sensory cilia act as cellular antennae, sensing environmental and morphogenic cues. Motile cilia, instead, are either used to propel cells themselves, or to move fluids over epithelia (e.g. in our lungs). Hence, cilia-related disorders (known as ciliopathies) affect many tissues and organs in various ways.
Ciliary dysfunction is the cause of an increasing number of single organ diseases and complex syndromic forms including hydrocephalus, infertility, airway diseases, polycystic diseases of the kidney, liver, or pancreas, as well as retinal diseases and defects of hearing and smelling.
The Pigino Group investigates the 3D structure of molecular components of cilia in their native cellular context and in isolation, trying to answer the question how they orchestrate cilia-specific functions. Our work typically positions itself right at the interface between structural biology and molecular cell biology. Hence, we are combining the latest tools and methodologies from both fields. These are ranging from cryo-electron tomography, over correlative light and fluorescence microscopy (CLEM), to in vitro reconstituted dynamic systems, genetics, biochemistry, image analysis methods, all the way to more classical cell biology.
The ultimate goal of the Pigino Group is to understand the underlying molecular causes of ciliary function and dysfunction, so that possible therapeutic strategies for ciliopathies can be developed.
Associate Head, Structural Biology Research Centre
01/2021 - Science
Posttranslational modifications of the microtubule cytoskeleton have emerged as key regulators of cellular functions, and their perturbations have been linked to a growing number of human pathologies. Tubulin glycylation modifies microtubules specifically in cilia and flagella, but its functional and mechanistic roles remain unclear. In this study, we generated a mouse model entirely lacking tubulin […]
09/2020 - Nature Structural Molecular Biology
Primary cilia are microtubule-based organelles that are important for signaling and sensing in eukaryotic cells. Unlike the thoroughly studied motile cilia, the three-dimensional architecture and molecular composition of primary cilia are largely unexplored. Yet, studying these aspects is necessary to understand how primary cilia function in health and disease. We developed an enabling method for […]
05/2016 - Science
The cilium is a large macromolecular machine that is vital for motility, signaling, and sensing in most eukaryotic cells. Its conserved core structure, the axoneme, contains nine microtubule doublets, each comprising a full A-microtubule and an incomplete B-microtubule. However, thus far, the function of this doublet geometry has not been understood. We developed a time-resolved […]
05/2012 - Journal of Structural Biology
Comparative structural analysis of eukaryotic flagella and cilia from Chlamydomonas, Tetrahymena, and sea urchins
Although eukaryotic flagella and cilia all share the basic 9 + 2 microtubule-organization of their internal axonemes, and are capable of generating bending-motion, the waveforms, amplitudes, and velocities of the bending-motions are quite diverse. To explore the structural basis of this functional diversity of flagella and cilia, we here compare the axonemal structure of three different organisms with […]
11/2011 - Journal of Cell Biology
Radial spokes (RSs) are ubiquitous components in the 9 + 2 axoneme thought to be mechanochemical transducers involved in local control of dynein-driven microtubule sliding. They are composed of >23 polypeptides, whose interactions and placement must be deciphered to understand RS function. In this paper, we show the detailed three-dimensional (3D) structure of RS in […]