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Centrioles are cytoplasmic structures whose distinguishing feature is an outer wall composed of a nine-fold symmetric array of stabilized microtubules. Centrioles perform two important functions in eukaryotic cells: 1) they form centrosomes that organize the microtubule cytoskeleton and contribute to cell division, and 2) they form cilia, cellular projections that perform critical sensory and motile functions. Reflecting their multiple roles in development and tissue homeostasis, centrosome and cilia abnormalities have been linked to cancer as well as developmental and adult disorders including ciliopathies, dwarfism and microcephaly. Work in my lab seeks to understand the fundamental and conserved molecular mechanisms underlying centriole assembly and their function in centrosome and cilium biogenesis.
In our lab we are using a combination of biochemical, cell biological and genetic approaches in the nematode C. elegans and the fruit fly D. melanogaster to investigate the fundamental and conserved molecular mechanisms underlying centriole assembly and function. In previous work we have used the C. elegans early embryo to define the molecular requirements for centriole assembly. The six-protein molecular pathway we identified has since been found to be conserved from ciliates to vertebrates, and is thought to form the core of the centriole assembly machinery in all eukaryotes. Current research builds on this foundation, seeking to answer three main questions: 1) How do centrioles assemble, and what are the molecular mechanisms that underlie their remarkable stability; 2) how do centrioles recruit pericentriolar material to form centrosomes and what is the molecular nature of this material; and 3) how do centrioles form cilia, focusing on the early events in ciliogenesis.
Following undergraduate studies at the University of Cambridge, a PhD at the Wellcome Centre for Cell Biology in Edinburgh and post-doctoral work at the Ludwig Insitute for Cancer Research in San Diego, Alex became a Junior Group Leader at the Max Perutz Labs in 2010 and in 2015 Associate Professor at the University of Vienna.
One of the main functions of centrioles is to serve as focal points for the recruitment of microtubule-organizing pericentriolar material (PCM). We previously showed that the PCM scaffold in C. elegans expands isotropically by incorporation of additional subunits throughout its volume (Laos et al., Curr Biol 2015). Thus, there is no privileged role for centrioles as docking sites for PCM assembly. However, this did not exclude an indirect, signaling role. To directly test centriole involvement we recently performed targeted laser ablation of centrioles at the onset of mitosis (Cabral, Laos et al., Dev Cell 2019). Unexpectedly, we found centrioles to be absolutely required for further PCM recruitment. Additionally, centrioles were required for centrosome structural integrity though not for maintenance of the PCM polymer per se. Thus, centrioles are certainly critical players throughout mitosis.
The other main function of centrioles, conserved in all species that possess them, is as basal bodies templating the formation of cilia. Ciliogenesis involves the docking of basal bodies to the plasma membrane and assembly of an elaborate gating structure, known as the transition zone, immediately distal to the basal body. Finally, the microtubule-based axoneme that serves the backbone of the cilium forms by direct extension of centriolar microtubules. Unusually, in C. elegans ciliated neurons, the basal body does not persist at the ciliary base, but degenerates during neuronal differentiation. Using a combination of light microscopy and electron tomography we showed that centrioles degenerate remarkably early in ciliogenesis, prior to expansion of the ciliary transition zone and axoneme elongation (Serwas et al., J Cell Biol 2017). Unlike in the case of centrosome assembly, centrioles are therefore required only for cilium initiation, but not directly involved in later steps of maturation and maintenance.
Centrioles are well known for the elaborate nine-fold symmetric architecture of their microtubule-based wall, which is essentially invariant from cell to cell and stably maintained over many generations and potentially the lifetime of the animal with no exchange of subunits with the surrounding cytoplasm. While considerable progress has been made in deciphering the molecular mechanisms underlying centriole assembly, how centrioles maintain their remarkable structural stability is not well understood. We recently identified the highly conserved centriolar protein Cep97 as a critical player in centriole stability and cilium assembly in Drosophila melanogaster (Dobbelaere et al, Curr Biol 2020). Cep97 stably binds mature centrioles and inhibits their dynamics. Loss of Cep97 results in an uncapping of centrioles and consequently shrinkage or elongation depending on cytoplasmic conditions.
An acentriolar centrosome at the C. elegans ciliary base.
Garbrecht, Joachim; Laos, Triin; Holzer, Elisabeth; Dillinger, Margarita; Dammermann, Alexander
Cep97 Is Required for Centriole Structural Integrity and Cilia Formation in Drosophila.
Dobbelaere, Jeroen; Schmidt Cernohorska, Marketa; Huranova, Martina; Slade, Dea; Dammermann, Alexander
Differential Requirements for Centrioles in Mitotic Centrosome Growth and Maintenance.
Cabral, Gabriela; Laos, Triin; Dumont, Julien; Dammermann, Alexander
The Group Dammermann participates in in the special Doctoral Program 'Chromosome Dynamics' reviewed and funded by the Austrian Research Fund FWF.
The Group Dammermann is an associate member of the Special Research Area (SFB) "Chromosome Dynamics - Unraveling the function of chromosomal domains" funded by the Austrian Science Fund FWF.
Project title: "Molecular Analysis of Centriole Assembly and Function"
Project title: "Identification and characterization of novel ciliogenesis factors"
Project title: "Molecular Analysis of Interphase Centrosomal Structures"
Project title: "Developing CryoEM/CLEM methods for analysis of cellular architecture"
Clementine Schouteden 2010, Gabriela Cabral 2012, Jeroen Dobbelaere 2013, Cornelia Rumpf-Kienzl 2015, Tiffany Su 2016, Claudia Pachinger 2019, Marketa Schmidt Cernohorska 2020
Genomic adaptation in red algae
Speaker: Hwan Su YoonInstitute: Sungkyunkwan University, KoreaHost: Fred Berger
Monday Seminar (Internal)
Speaker: TERIYAPIROM Isaree (Koo), NAVA GARCIA Marintia Mayola (Dagdas), AYALA MUNOZ Farja (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Protein synthesis programs the development and evolution of neuronal diversity
Speaker: Matthew KrausharInstitute: MPI for Molecular Genetics, BerlinHost: Andrea Pauli
Monday Seminar (Internal)
Speaker: OTSUKI Leo (Tanaka), LEITNER Marie-Christin (Mendjan), SEONG Jinwoo (Rivron)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Mark DawsonInstitute: Peter MacCallum Cancer CentreHost: Johannes Zuber
Monday Seminar (Internal)
Speaker: HOLZMANN Viktoria (Rivron), LEV Itamar (Zimmer), HODAKOVA Zuzana (Haselbach)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Developmental flexibility to keep pace with a changing world
Speaker: Dominique BergmannInstitute: Stanford UniversityHost: Liam Dolan
Monday Seminar (Internal)
Speaker: BABADEI Olga (Decker), KELLNER Max Josef (Penninger), DENEKE Victoria (Pauli)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Role of the centromere in genetic self/non-self discrimination in yeasts
Speaker: Yves BarralInstitute: ETH ZurichHost: Shotaro Otsuka
The Shape of Things to Come
The Shape of Things to come
is a 3-day Exhibition Event merging scientific & artistic projects in a digital environment (Mixed Reality (XR) > Augmented & Virtual Reality | AR & VR)
Monday Seminar (Internal)
Speaker: TAKACS Zsuzsanna (Gerlich), DE LA CONCEPCION Juan Carlos (Dagdas), FEDL Anna (Busslinger)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Developmental Origins of Health and Disease and the Preimplantation Window
Speaker: Sophie PetropoulosInstitute: Karolinska InstitutetHost: Nicolas Rivron
Monday Seminar (Internal)
Speaker: GALLI Lucrezia (Tanaka), HORN Sabrina (Peters), JACOBS Jelle (Stark)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
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Next Generation of 3D Cell Culture, Magnetic 3D Cell Culture and Bioprinting
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Mechanisms of folding and assembly of newly synthesized proteins
Speaker: Bernd BukauInstitute: ZMBHHost: Elif Karagäz
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Regulation of protein biogenesis in health and disease
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Monday Seminar (Internal)
Speaker: CHUGUNOVA Anastasia (Pauli), RÖTZER Johannes (Dolan), JONSSON Gustav (Penninger)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
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Title to be announced
Speaker: Lacra BintuInstitute: Stanford UniversityHost: Alex Stark
Monday Seminar (Internal)
Speaker: DIEZMA Laura (Nordborg/Mari-Ordonez), GHOSH Dipannita (Grade), PATEL Rajvi (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be annouced
Speaker: Adele MarstonInstitute: Wellcome Centre Cell Biology, University of EdinburghHost: Daniel Gerlich, Joao Matos
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
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Title to be announced
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Title to be announced
Speaker: Ron DrorInstitute: Stanford UniversityHost: David Haselbach
Monday Seminar (Internal)
Speaker: VOJTEK Matus (Stark), LEHMANN Christian (Knoblich), LEE Du-Hwa (Belkhadir)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Petra SchwilleInstitute: MPI of BiochemistryHost: Alwin Köhler
Monday Seminar (Internal)
Speaker: SPICER Maximilian (Gerlich), ESTIVILL I CAPAAROS Guillem (Obenauf), MURPHY Paul (Clausen)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Imaging processes of cell division across scales
Speaker: Jan EllenbergInstitute: EMBL HeidelbergHost: Shotaro Otsuka
Monday Seminar (Internal)
Speaker: JÄGER Christina (Van der Veeken), PRADHAN Saurabh (Rivron), RAFANEL Baptiste (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Title to be announced
Speaker: Dirk InzeInstitute: VIBHost: Andreas Bachmair
Title to be announced
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Monday Seminar (Internal)
Speaker: BAUCELLS Julia (Dammermann), PANAROTTO-PERICLES Melanie (Peters), VOICHEK Maya Shinan (Brennecke)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Maria LlorensInstitute: CBMHost: Noelia Urban
Monday Seminar (Internal)
Speaker: DMITRIEV Vladimir (Goloborodko), HISANAGA Tetsuya (Berger), KHALDIEH Nina (Ameres)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: SOMMER Theresa (Rivron), SHIRZADIAN YAZD Mehrta (Balzarotti), VERTESY Abel (Knoblich)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: POLIKARPOVA Anastasia (Tanaka), CHAKRABORTY Oisorjo (Grade), CORSI Flavia (Goloborodko)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: FESSELET Jeanne (Kovarik), KHAURATOVIC Uladzislava (Matos/Golobordko), SHEN Jingyi (Obenauf)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Roger GeigerInstitute: Institute for Research in Biomedicine, BellinzonaHost: Joris Van der Veeken
Monday Seminar (Internal)
Speaker: PERNEBRINK Mattias (Tanaka), HOHMANN Ulrich (Brennecke/Plaschka), MANOLOVA Toni (Falk)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: WU Shuangyang (Dolan), SCARAMUZZA Federico (Tessmar), KROGULL Daniel (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Joanna WysockaInstitute: Stanford School of MedicineHost: Christa Bücker
Monday Seminar (Internal)
Speaker: HEIDARI KHOEI Heidar (Rivron), BELL Caelan (Gerlich), GALUSKA Philipp (Djinovic)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Daniele CanzioInstitute: UCSFHost: Anton Goloborodko
Monday Seminar (Internal)
Speaker: ABDRAKHMANOV Alibek (Dagdas), WILLIAMS Thomas (Clausen), GEISMANN Maximilian (Balzarotti)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: NAGUMO WONG Sakurako (Knoblich), LORENZO ORTS Laura (Pauli), ROSS James (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: RAFFL Gerald (Ameres), SAJTOS Bettina (Zuber), ISHIHARA Keisuke (Tanaka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Anshul KundajeInstitute: Stanford UniversityHost: Alex Stark
Monday Seminar (Internal)
Speaker: STEINACKER Thomas (Gerlich), EDER Stephanie (Zimmer), TIKANOVA Polina (Burga)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: SCHELLHAAS Ulla (Plaschka/Ameres), RUSCH Emma (Goloborodko), CLAVEL Marion (Dagdas)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: RÖHSNER Josef (Pauli), OKUN Anastasia (Karagöz), JUNG Pauline (Obenauf)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: LICHT-MAYER Simon (Penninger), CAYGILL Samuel (Dolan), MIGOTTI Mario (Konrat)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Feng ShaoInstitute: National Institute of Biological Sciences, BeijingHost: Pavel Kovarik
Monday Seminar (Internal)
Speaker: SHUNMUGAM Dhanlakshmi (Baccarini), CECI GINISTRELLI Lavinia (Mendjan), VORLÄNDER Matthias (Plaschka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Lydia FinleyInstitute: Memorial Sloan Kettering Cancer CenterHost: Johannes Zuber
Monday Seminar (Internal)
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Title to be announced
Speaker: Stephan GruberInstitute: University of LausanneHost: Franz Klein
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Title to be announced
Speaker: Nancy KlecknerInstitute: Harvard UniversityHost: Franz Klein
Monday Seminar (Internal)
Speaker: GRABARCZYK Daniel (Clausen), PROTELL I DE MONTSERRAT Julia (Brennecke/Plaschka), MANCHENO JUNCOSA Estela (Mendjan)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Title to be announced
Speaker: Edward LemkeInstitute: IMB MainzHost: David Haselbach
Monday Seminar (Internal)
Speaker: ATTRILL Sarah (Dolan), UIJTTEWAAL Esther (Elling), SCIBISZ Grzegorz (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Title to be announced
Speaker: Rotem SorekInstitute: Weizmann Institute of Science, RehovotHost: Julius Brennecke
Monday Seminar (Internal)
Speaker: HORENKAMP Simone (Tanaka), CASEY Chloe (Dolan), KAPRAL Thomas (Zagrovic)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
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Title to be announced
Speaker: Mounia LaghaInstitute: Institut de Genetique Moleculaire de MontpellierHost: Andrea Pauli
Monday Seminar (Internal)
Speaker: LEITNER Moritz (Martinez), VOGEL Alexander (Yudushkin), KETTEL Paulina (Karagöz)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: TSAREV Aleksandr (Ameres), FIESELER Charlie (Zimmer), ABESAMIS Kim Ivan (Dong)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: STREUBEL Susanna (Dolan), KLEIFELD Justus (Urban), ORLIC Lucija (Matos)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
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Monday Seminar (Internal)
Speaker: KOLLER Manuela (Campbell), GUPTA Ankit (Goloborodko), SCHMÖLLERL Johannes (Zuber)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: MARCHIORI Elisa (Van der Veeken), ACHLEITNER Anja (Martens), FAAS Victoria (Clausen)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: SALEWSKIJ Kirill (Penninger), KIRCHGATTERER Paul (Gaidt), REN Kaike (Otsuka)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
Monday Seminar (Internal)
Speaker: MIHAILOVIC Milica (Karagöz), BELL Lillie (Clausen)Institute: Open only to IMP/IMBA/GMI/Max Perutz Labs
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