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

  • 07/2020 - BiologyOpen

    Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells

    Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation […]

  • 05/2020 - Molecular Biology of the Cell

    Reorganization of budding yeast cytoplasm upon energy depletion

    Yeast cells, when exposed to stress, can enter a protective state in which cell division, growth, and metabolism are down-regulated. They remain viable in this state until nutrients become available again. How cells enter this protective survival state and what happens at a cellular and subcellular level are largely unknown. In this study, we used […]

  • 08/2019 - Scientific Reports

    Microridges are apical epithelial projections formed of F-actin networks that organize the glycan layer

    Apical projections are integral functional units of epithelial cells. Microvilli and stereocilia are cylindrical apical projections that are formed of bundled actin. Microridges on the other hand, extend laterally, forming labyrinthine patterns on surfaces of various kinds of squamous epithelial cells. So far, the structural organization and functions of microridges have remained elusive. We have […]

  • 07/2019 - Current Opinion in Structural Biology

    Towards a mechanistic understanding of cellular processes by cryoEM

    A series of recent hardware and software developments have transformed cryo-electron microscopy (cryoEM) from a niche tool into a method that has become indispensable in structural and functional biology. Samples that are rapidly frozen are encased in a near-native state inside a layer of amorphous ice, and then imaged in an electron microscope cooled to […]

  • 07/2019 - Methods in Cell Biology

    Content-aware image restoration for electron microscopy

    Multiple approaches to use deep neural networks for image restoration have recently been proposed. Training such networks 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. Here we summarize on a number of recent developments in the […]