Cells need to be able to sense different types of signals, such as chemical and mechanical signals, from the extracellular environment to properly function. Most eukaryotic cells perform these functions through a specialized hair-like organelle, the cilium, that extends from the cell body as a sort of antenna. The signaling and sensory functions of cilia are fundamental already during the early stages of embryo development, when cilia coordinate the establishment of the internal left/right asymmetry typical of the vertebrate body. Later, cilia continue to be required for the correct development and function of specific tissues and organs, such as brain, heart, kidney, liver, and pancreas. Sensory cilia eventually allow us to sense the environment that surrounds us, for instance we see through the connecting cilium of photoreceptors in our retina, we smell through the sensory cilia at the tip of our olfactory neurons, and we hear thanks to the kinocilium of our sensory hair cells. Motile cilia, which themselves have sensory functions, also work as propeller-like extensions that allow us to breath, because they keep our lungs clean, to reproduce, because they propel sperm cells, and even to properly reason, because they contribute to the flow of cerebrospinal fluid in our brain ventricles. Not surprisingly, defects in the assembly and function of these tiny organelles result in devastating pathologies, which are collectively known as ciliopathies. Thus, proper function of cilia is fundamental for human health.
The Pigino Lab investigates the biology and the 3D molecular structure of ciliary components in their native cellular context and in isolation, to understand how they orchestrate cilia-specific functions. Our work positions itself right at the interface between structural biology and molecular cell biology. Hence, we combine the latest tools and methodologies from both fields, 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.
Our ultimate goal is to understand the underlying molecular mechanisms of ciliary functions and dysfunctions, so that possible therapeutic strategies for ciliopathies can be developed.
Associate Head of 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 […]