Pigino
Structural biology

Pigino Group

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.

 

ERC funded project (ERC-2018-COG N#819826 CiliaTubulinCode)
Self-organization of the cilium: the role of the tubulin code
Our current knowledge of the basic principles which lead to self-organization of cellular organelles is quite limited. Hence, our project aims at understanding the role of the tubulin code for self-organization of complex microtubule based cellular structures, with the focus on the structure of the cilium.

Group members

Publications

  • 05/2019 - Methods in Cell Biology

    In situ cryo-electron tomography and subtomogram averaging of intraflagellar transport trains

    In situ cryo-electron tomography (cryo-ET) and subtomogram averaging are powerful tools, able to provide 3D structures of biological samples at sub-nanometer resolution, while preserving information about cellular context and higher-order assembly. Best results are typically achieved, when applied to highly repetitive structures, such as viruses. Other typical examples are protein complexes that decorate long stretches along ciliary microtubules at […]

  • 11/2018 - Nature Cell Biology

    The cryo-EM structure of intraflagellar transport trains reveals how dynein is inactivated to ensure unidirectional anterograde movement in cilia

    Movement of cargos along microtubules plays key roles in diverse cellular processes, from signalling to mitosis. In cilia, rapid movement of ciliary components along the microtubules to and from the assembly site is essential for the assembly and disassembly of the structure itself1. This bidirectional transport, known as intraflagellar transport (IFT)2, is driven by the […]

  • 10/2018 - ArXiv

    Cryo-CARE: Content-Aware Image Restoration for Cryo-Transmission Electron Microscopy Data

    Multiple approaches to use deep learning for image restoration have recently been proposed. Training such approaches requires well registered pairs of high and low quality images. While this is easily achievable for many imaging modalities, e.g. fluorescence light microscopy, for others it is not. Cryo-transmission electron microscopy (cryo-TEM) could profoundly benefit from improved denoising methods, […]

  • 10/2017 - Molecular Biology of the Cell

    Microtubule dynamics: 50 years after the discovery of tubulin and still going strong

    The Minisymposium “Microtubule Dynamics” featured speakers ranging from a founding member of the microtubule field to graduate students embarking on their scientific journeys. The session spanned a broad range of topics, from fundamental questions about the structure and dynamics of microtubules, to the behavior of molecular motors in reconstituted systems, to the therapeutic potential of […]

  • 07/2017 - Nature Structural & Molecular Biology

    Switching dynein motors on and off

    Cytoplasmic dyneins transport cellular components from the periphery toward the center of the cell. By moving cargoes along microtubules, dyneins ensure proper cell division, regulate exchange of materials between organelles, and contribute to the internal organization of eukaryotic cells. Two recent studies show that, upon dimerization, cytoplasmic dyneins intrinsically adopt an autoinhibited configuration that can […]