Q&A: Who needs a centrosome?

The centrosome has several functions. The central one is as the major microtubule organizing center (MTOC) in proliferating animal cells: thus, it helps to organize the microtubules that form the mitotic spindle in dividing cells, and orchestrate a wide variety of cellular processes, including cell motility, signaling, adhesion, coordination of protein trafficking by the microtubule cytoskeleton and the acquisition of polarity. The centrosome has crucial links to the nucleus, the Golgi, cell to cell junctions and acto-myosin cytoskeleton that are very important in positioning it and thus shaping the microtubule cytoskeleton in relation to the cell and the organism (reviewed in [1]). The role of the centrosome in organizing cellular microtubules can differ from cell to cell and be regulated differently in different phases of the life of a cell.Laboratório Associado de Oeiras, EMBO Installation Grant: (co-funded by FCT and Instituto Gulbenkian de Ciência), FCT, Instituto Gulbenkian de Ciência

Patterns of selection against centrosome amplification in human cell lines.

The presence of extra centrioles, termed centrosome amplification, is a hallmark of cancer. The distribution of centriole numbers within a cancer cell population appears to be at an equilibrium maintained by centriole overproduction and selection, reminiscent of mutation-selection balance. It is unknown to date if the interaction between centriole overproduction and selection can quantitatively explain the intra- and inter-population heterogeneity in centriole numbers. Here, we define mutation-selection-like models and employ a model selection approach to infer patterns of centriole overproduction and selection in a diverse panel of human cell lines. Surprisingly, we infer strong and uniform selection against any number of extra centrioles in most cell lines. Finally we assess the accuracy and precision of our inference method and find that it increases non-linearly as a function of the number of sampled cells. We discuss the biological implications of our results and how our methodology can inform future experiments

Maintaining centrosomes and cilia

The deposited item is a review and has been submitted to peer review. This publication hasn't any creative commons license associated. There is no public supplementary material available for this publication.Centrosomes and cilia are present in organisms from all branches of the eukaryotic tree of life. These structures are composed of microtubules and various other proteins, and are required for a plethora of cell processes such as structuring the cytoskeleton, sensing the environment, and motility. Deregulation of centrosome and cilium components leads to a wide range of diseases, some of which are incompatible with life. Centrosomes and cilia are thought to be very stable and can persist over long periods of time. However, these structures can disappear in certain developmental stages and diseases. Moreover, some centrosome and cilia components are quite dynamic. While a large body of knowledge has been produced regarding the biogenesis of these structures, little is known about how they are maintained. In this Review, we propose the existence of specific centrosome and cilia maintenance programs, which are regulated during development and homeostasis, and when deregulated can lead to disease.Fundação para a Ciência e a Tecnologia grants: (SFRH/BPD/79680/2011, SFRH/BD/52176/2013); ERC grant: (ERC-2015-CoG - 683258_CentrioleBirthDeath).info:eu-repo/semantics/publishedVersio

Mapping molecules to structure: unveiling secrets of centriole and cilia assembly with near-atomic resolution

The deposited article is a post-print version and has been subjected to peer review.This publication hasn't any creative commons license associated.There is no public supplementary material available.Centrioles are microtubule (MT)-based cylinders that form centrosomes and can be modified into basal bodies that template the axoneme, the ciliary MT skeleton. These MT-based structures are present in all branches of the eukaryotic tree of life, where they have important sensing, motility and cellular architecture-organizing functions. Moreover, they are altered in several human conditions and diseases, including sterility, ciliopathies and cancer. Although the ultrastructure of centrioles and derived organelles has been known for over 50 years, the molecular basis of their remarkably conserved properties, such as their 9-fold symmetry, has only now started to be unveiled. Recent advances in imaging, proteomics and crystallography, allowed the building of 3D models of centrioles and derived structures with unprecedented molecular details, leading to a much better understanding of their assembly and function. Here, we cover progress in this field, focusing on the mechanisms of centriole and cilia assembly.Portuguese Foundation for Science and Technology (FCT) grants: (HMSP-CT/SAU-ICT/0075/2009,PTDC/BIA-BCM/105602/2008, PTDC/BIA-BCM/112736/2009, PTDC/SAU-OBD/105616/2008); BPD Fellowship; Harvard Medical School; EMBO installation grant; ERC starting grant.info:eu-repo/semantics/publishedVersio

A structural road map to unveil basal body composition and assembly

The deposited article is a post-print version and has been submitted to peer review.This publication hasn't any creative commons license associated.There is no public supplementary material available.The Basal Body (BB) acts as the template for the axoneme, the microtubule‐basedstructure of cilia and flagella. Although several proteins were recently implicatedin both centriole and BB assembly and function, their molecular mechanisms are stillpoorly characterized. In this issue of The EMBO journal, Li and coworkersdescribe for the first time the near‐native structure of the BB at 33 Åresolution obtained by Cryo‐Electron Microscopy analysis of wild‐type (WT) isolatedChlamydomonas BBs. They identified several uncharacterized non‐tubulinstructures and variations along the length of the BB, which likely reflect thebinding and function of numerous macromolecular complexes. These complexes areexpected to define BB intrinsic properties, such as its characteristic structure andstability. Similarly to the high‐resolution structures of ribosome and nuclear porecomplexes, this study will undoubtedly contribute towards the future analysis ofcentriole and BB biogenesis, maintenance and function.Fundação para a Ciência e Tecnologia grant: (PTDC/BIA‐BCM/105602/2008); EMBO Installation Grant; Instituto Gulbenkian de Ciência; ERC grant(261344—CentriolStructNumber).info:eu-repo/semantics/publishedVersio

Noncanonical Biogenesis of Centrioles and Basal Bodies

The deposited article is a pre-print version.The deposited article version is the Epub Ahead of Print version of the article, posted online 23 April 2018, provided by Cold Spring Harbor Laboratory Press. It hasn't peer-review.This deposit is composed by the main article, and it hasn't any supplementary materials associated.Centrioles and basal bodies (CBBs) organize centrosomes and cilia within eukaryotic cells. These organelles are composed of microtubules and hundreds of proteins performing multiple functions such as signaling, cytoskeleton remodeling, and cell motility. The CBB is present in all branches of the eukaryotic tree of life and, despite its ultrastructural and protein conservation, there is diversity in its function, occurrence (i.e., presence/absence), and modes of biogenesis across species. In this review, we provide an overview of the multiple pathways through which CBBs are formed in nature, with a special focus on the less studied, noncanonical ways. Despite the differences among each mechanism herein presented, we highlighted some of their common principles. These principles, governing different steps of biogenesis, ensure that CBBs may perform a multitude of functions in a huge diversity of organisms but yet retained their robustness in structure throughout evolution.European Research Council Consolidator Grant: (CoG683528__Centriole-BirthDeath); Boehringer Ingelheim Fonds; Fundação para a Ciência e Tecnologia grant: (PD/BD/114350/2016).info:eu-repo/semantics/acceptedVersio

Drosophila melanogaster as a model for basal body research

No supplementary material available.The fruit fly, Drosophila melanogaster, is one of the most extensively studied organisms in biological research and has centrioles/basal bodies and cilia that can be modelled to investigate their functions in animals generally. Centrioles are nine-fold symmetrical microtubule-based cylindrical structures required to form centrosomes and also to nucleate the formation of cilia and flagella. When they function to template cilia, centrioles transition into basal bodies. The fruit fly has various types of basal bodies and cilia, which are needed for sensory neuron and sperm function. Genetics, cell biology and behaviour studies in the fruit fly have unveiled new basal body components and revealed different modes of assembly and functions of basal bodies that are conserved in many other organisms, including human, green algae and plasmodium. Here we describe the various basal bodies of Drosophila, what is known about their composition, structure and function.EMBO installation grant; European Research Council; Instituto Gulbenkian de Ciência; Fondation pour la recherche Médicale grant: (FRM DEQ 20131029168).info:eu-repo/semantics/publishedVersio

Centrosomes and cilia in human disease

The deposited article is a post-print version (NIH-PA Author Manuscript) and has been submitted to peer review.There is no public supplementary material available for this publication.This publication hasn't any creative commons license associated.Centrioles are microtubule-derived structures that are essential for the formation of centrosomes, cilia and flagella. The centrosome is the major microtubule organiser in animal cells, participating in a variety of processes, from cell polarisation to cell division, whereas cilia and flagella contribute to several mechanisms in eukaryotic cells, from motility to sensing. Although it was suggested more than a century ago that these microtubule-derived structures are involved in human disease, the molecular bases of this association have only recently been discovered. Surprisingly, there is very little overlap between the genes affected in the different diseases, suggesting that there are tissue-specific requirements for these microtubule-derived structures. Knowledge of these requirements and disease mechanisms has opened new avenues for therapeutical strategies. Here, we give an overview of recent developments in this field, focusing on cancer, diseases of brain development and ciliopathies.Fundação para a Ciência e Tecnologia; Fundação Calouste Gulbenkian; European Molecular Biology Organization; European Research Council; NIH grants: (DK068306, DK090917); Howard Hughes Medical Institute.info:eu-repo/semantics/publishedVersio

Comunicar ciência em Portugal: uma avaliação das perspectivas para o estabelecimento de formas de diálogo entre cientistas e o público

Este artigo avalia as perspectivas para o estabelecimento de formas de comunicação directa e bidireccional (diálogo) entre cientistas e o público, em Portugal, em substituição da comunicação indirecta e unidireccional, actualmente prevalecente. Um maior envolvimento do público com a ciência requer meios de comunicação que promovam o diálogo entre cientistas e o público, permitindo partilhar os valores e o sistema social da ciência. Neste sentido, organizámos e avaliámos uma conferência de fim-de-semana pioneira em Portugal, entre cientistas do Instituto Gulbenkian de Ciência (IGC), um instituto de investigação biomédica, e o público de Oeiras, onde o instituto se localiza. O formato da conferência foi adaptado do modelo dinamarquês das conferências de consenso, que são um meio exemplar para o diálogo. Estiveram envolvidos dois painéis: um painel leigo, constituído por membros do público, e um painel de cientistas, constituído por investigadores do IGC. O painel leigo estabeleceu a agenda da conferência, conduziu as sessões e preparou um relatório de consenso. A avaliação e as consequências desta conferência de fim-de-semana sugerem que o diálogo entre cientistas e o público é possível, viável e que promove maior envolvimento do público com a ciência

Strategies to promote science communication: organisation and evaluation of a workshop to improve the communication between Portuguese researchers, the media and the public

As western societies become increasingly dependent on scientific and technological developments, the full exercise of citizenship requires the ability to understand those developments. Scientists should be able to make this progress meaningful to different communities and to discuss its implications. However, science communication is still not part of the formal education of researchers. We organized a pioneering workshop in Portugal, Comunicar Ciência (‘Comunicating Science’), at the Gulbenkian Institute of Science (10-12 September 2003). In this workshop, 17 Portuguese scientists, from PhD students to heads of research institutes, experienced a plethora of practical exercises organised by journalists and science communication experts from Portugal and the UK. Summary and follow-up evaluations show that scientists feel more confident in their communication skills and ability to participate in activities after the workshop. This work suggests that when targeting the right people, a small, low budget activity, such as this science communication workshop, can improve the participation of scientists in science communication activities