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Guest Group: Cilia and Stem Cells in Sensory Systems

PI: Andreas Gießl

Focus

My group has a broad background and expertise in molecular biology and neuroscience. My research includes the analysis of disease mechanisms and fundamental processes in the cornea, photoreceptor cells and ciliogenesis in general. The main interests are the basic cellular mechanisms by which cytoskeletal elements and protein complexes work together to regulate the distribution of molecules in the morphologically and functionally distinct compartments of these tissues.

Possible role of proteins in the ciliary transport in ciliated sensory Neurons

One spotlight in ciliary research is the protein Pericentrin (Pcnt) – also known in human as Kendrin. This protein is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome. My group studies the mammalian centrosomal/ciliary scaffold protein in the retina and created an interactome of Pcnt through various experiments. In the retina, Pcnt co-localizes with the whole protein transport machinery from the inner to the outer segment of photoreceptor cells. Studying Pcnt function may help us to understand the regulation of protein transport in photoreceptor cells and provide new insights into human disorders related to defects in ciliary function.

 

Interactions between stem cells and their microenvironment in the human limbal niche

Another focus of my research are stem cells in the cornea. The corneal epithelium acts as a protective barrier on the anterior ocular surface and is essential for corneal transparency and visual function. During both homeostasis and repair, the corneal epithelium is maintained by self-renewing stem/progenitor cells at a transition zone termed limbus, which separates the cornea from the surrounding conjunctiva. Depletion of this stem cell reservoir and/or destruction of its niche microenvironment can cause severe ocular surface disease and significant visual deterioration. Our goal is to analyze this niche microenvironment, regulating the stem cell activities, to replicate the biological niche in vitro, and to establish stem cell based therapies for ocular surface disorders.

 

Methods

In our experimental approach, we combine neuroanatomical, immunocytochemical, biochemical, molecular, cell biological and physiological methods to investigate the sensory tissues of human, wild type and genetically modified mice.

Scientist at FAU Erlangen-Nürnberg, Using the ChemiDoc™ MP Imaging System

Support

Deutsche Forschungsgemeinschaft DFG (Einzelförderung GI 770)
Dr. Hertha und Helmut Schmauser-Stiftung
Universitätsbund Erlangen-Nürnberg e.V.

Collaborations

My projects are embedded in international collaborations as well as in scientific networks at the University of Erlangen-Nuremberg.

PD Dr. Christian Thiel, Institute of Human Genetics, University of Erlangen-Nuremberg, Germany

Prof. Ronald Roepman, Department of Human Genetics, Molecular Biology of Ciliopathies, Radboud University Nijmegen Medical Centre, Netherlands

Prof. J. Kremers, Department of Ophthalmology, University of Erlangen- Nuremberg, German

Prof. Dr. Felix B. Engel, Nephropathologische Abteilung, University of Erlangen-Nuremberg, Germany

Dr. Stefan Geimer, Electron Microscopy Laboratory, Institute for Cell Biology, University of Bayreuth, Germany

Prof. Dr. Marius Ueffing, Dr. Karsten Boldt, Institute for Ophthalmic Research, Molecular Biology of Retinal Degenerations, University of Tübingen, Germany

Prof. Dr. Ralf Enz, Institute for Biochemistry, University of Erlangen-Nuremberg, Germany

Prof. Dr. Uwe Wolfrum, Department of Cell and Matrix Biology, Johannes Gutenberg-University Mainz, Germany

Prof. Regina Trollmann, Pediatric Clinic, University of Erlangen-Nuremberg, Germany

Prof. Michel Cayouette, Vasanth Ramamurthy, Department of Biology, Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montreal (IRCM), Montreal, Canada

Prof. Yoshitaka Ono, Prof. Mikiko Takahashi, Biosignal Research Center, Kobe University, Japan

Selected Publications

  • Falk N, Kessler K, Schramm SF, Boldt K, Becirovic E, Michalakis S, Regus-Leidig H, Noegel AA, Ueffing M, Thiel CT, Roepman R, Brandstätter JH, Gießl A (2018) Functional analyses of Pericentrin and Syne-2 interaction in ciliogenesis. J Cell Sci; 131(16); doi: 10.1242/jcs.218487.
  • Kurtenbach S, Gießl A, Strömberg S, Kremers J, Atorf J, Rasche S, Neuhaus EM, Hervé D, Brandstätter JH, Asan E, Hatt H, Kilimann MW (2017) The BEACH protein LRBA promotes the localization of the heterotrimeric G-protein Golf to olfactory cilia. Sci Rep; 7(1):8409; doi: 10.1038/s41598-017-08543-4.
  • Nguyen ON, Böhm S, Gießl A, Butz ES, Wolfrum U, Brandstätter JH, Wahl-Schott C, Biel M, Becirovic E (2016) Peripherin-2 differentially interacts with cone opsins in outer segments of cone photoreceptors. Hum Mol Genet, 25(12):2367-77; doi: 10.1093/hmg/ddw103.
  • Gotthardt K, Lokaj M, Koerner C, Falk N, Gießl A, Wittinghofer A (2015) A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. eLife; 4:e11859;
    Falk N, Lösl M, Schröder N, Gießl A (2015) Specialized Cilia in Mammalian Sensory Systems. Special Issue Cilia and Flagella: Biogenesis and Function. Review. Cells; 4(3), 500-519.
  • Wheway G, Schmidts M, Mans DA, …, Boldt K, Parry DA, Letteboer SJF,…, Kessler K, Gießl A,…,Thiel CT, Boycott KM, McKibbin M, Inglehearn CF, UK10K Consortium, University of Washington Center for Mendelian Genomics,…, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, Johnson CA (2015) An siRNA-based functional genomics screen for the identification of novel regulators of ciliogenesis and ciliopathy genes. Nat Cell Biol; 17(8):1074-87.
  • Zebrowski DC, Vergarajauregui S, Wu CC, Piatkowski T, Becker R, Leone M, Hirth S, Ricciardi F, Falk N, Gießl A, Just S, Braun T, Weidinger G, Engel FB (2015) Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes. eLife; 4:e05563.
  • Kessler K, Wunderlich I, Uebe S, Falk NS, Gießl A, Brandstätter JH, Popp B, Klinger P, Ekici AB, Sticht H, Dörr HG, Reis A, Roepman R, Seemanová E, Thiel CT (2015) DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects. Sci Rep; 5:11649.
  • Mühlhans J, Gießl A (2012) Pericentrin in health and disease: Exploring the patchwork of Pericentrin splice variants. Commun Integr Biol; 5(4):304-7.
  • Mühlhans J, Brandstätter JH, Gießl A (2011) The Centrosomal Protein Pericentrin Identified at the Basal Body Complex of the Connecting Cilium in Mouse Photoreceptors. PLoS One; 6(10):e26496.
  • Thiel C, Kessler K, Gießl A, Dimmler A, Shalev SA, von der Haar S, Zenker M, Zahnleiter D, Stöss H, Beinder E, Abou Jamra R, Ekici AB, Schröder-Kress N, Aigner T, Kirchner T, Reis A, Brandstätter JH, Rauch A (2011) NEK1 mutations cause Short-Rib Polydactyly Syndrome Type Majewski. Am J Hum Genet; 88(1):106-114.
  • Gießl A, Trojan P, Rausch S, Pulvermüller A, Wolfrum U (2006) Centrins, gatekeepers for the light dependent translocation of transducin through the photoreceptor cell connecting cilium. Vision Res; 46: 4502-4509.
  • Gießl A, Pulvermüller A, Trojan P, Park JH, Choe H-W, Ernst OP, Hofmann KP, Wolfrum U (2004) Differential expression and interaction with the visual G-Protein transducin of centrin isoforms in mammalian photoreceptor cells. J Biol Chem; 279(49): 51472-81.

Publications in PubMed