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Return to: College of Biological Sciences: Medical School: U of M Home |
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Areas of Research Strength: Investigations of Ciliary and Flagellar Microtubules at Molecular, Cellular and Developmental Levels back to top |
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Research Techniques: protein biochemistry immunochemistry molecular biology molecular genetics light & electron microscopy back to top |
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Research Interests: The research focus of the Linck lab concerns the molecular biology of microtubules in centrioles, cilia, and flagella in normal cellular function, development and disease. Centrioles are essential in the cell cycle and cell division, and they differentiate into basal bodies to form cilia and flagella, which are present in protists and all animal species. Cilia and flagella are used for cellular propulsion (e.g., sperm) or for transporting extra-cellular substances (e.g., embryonic fluid, oviduct and tracheal contents, and cerebrospinal fluid). Cilia also function in sensory cells, e.g., in retinal photoreceptors and olfactory neurons. Human diseases and conditions in which cilia are affected include infertility, respiratory disorders, polycystic kidney disease, and situs inversus (left-right reversal of organs). The lab uses different model systems and techniques suited to answer the appropriate questions at molecular, cellular and developmental levels. From sea urchins and mice we cloned novel genes encoding proteins (the tektin family) that are associated with a specialized set of microtubule protofilaments in cilia, flagella, basal bodies and centrioles. From molecular and structural studies the lab developed the hypothesis that tektins and associated proteins form molecular templates and rulers in these microtubules. Molecular genetic studies, found tektin expression to be remarkable in mammalian testis, lung, brain and sensory tissues (e.g., choroid plexus, retina and olfactory epithelia), indicative of the presence of both motile and non-motile cilia in these tissues. The lab has used the biflagellate, single-celled alga, Chlamydomonas, to clone two additional genes for proteins associated with the specialized microtubule protofilaments. Like tektins, these genes have close homologues in mouse and human. Currently, the lab is using sea urchin sperm flagella (in conjunction with Chlamydomonas) to analyze the structure of tektin filaments and their associations with inner dynein arms, radial spokes and nexin links. Students working in this lab can learn a variety of valuable technical skills, including protein biochemistry, immunochemistry, molecular biology, and light & electron microscopy. back to top |
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Selected Publications: Linck, R.W., & Stephens, R.E. (2007) Functional Protofilament Numbering of Ciliary, Flagellar and Centriolar Microtubules. Cell Motil. Cytoskeleton 64, 489-495. Setter, P.W., Malvey-Dorn E., Steffen W. Stephens R.E., & Linck R.W. (2006) Tektin interactions and a model for molecular functions. Exp. Cell Res. 312, 2880-2896. Linck, R.W., & Norrander, J.M. (2003) Protofilament ribbon compartments of ciliary and flagellar microtubules. Protist 154, 299-311. Ikeda, K., Brown, J.A., Yagi, T., Norrander, J.M., Hirono, M., Eccleston, E.D., Kamiya, R., & Linck, R.W. (2003) Rib72, a conserved protein associated with the ribbon compartment of flagellar A-microtubules and potentially involved in the linkage between outer doublet microtubules. J. Biol. Chem. 278, 7725-7734. Larsson, M., Norrander, J., Gräslund, S., Brundell, E., Linck, R., Ståhl, S., and Höög, C. (2000) The spatial and temporal expression of Tekt1, a mouse tektin C homologue, during spermatogenesis suggest that it is involved in the development of the sperm tail basal body and axoneme. Eur. J. Cell Biol. 79, 718-725. Linck, R.W. (2000) Cilia and Flagella. http://www.els.net Norrander, J.M., deCathelineau, A.M., Brown, J.A., Porter, M.E., and Linck, R.W. (2000) The rib43a protein is associated with forming the specialized protofilament ribbons of flagellar microtubules in Chlamydomonas. Mol. Biol. Cell. 11, 201-215. Norrander, J., Larsson, M., Ståhl, S., Höög, C., and Linck, R. (1998) Expression of ciliary tektins in brain and sensory development. J. Neurosci. 18, 8912-8918. Hinchcliffe, E.H., and Linck, R.W. (1998) Two proteins isolated from sea urchin sperm flagella: structural components common to the stable microtubules of axonemes and centrioles. J. Cell Sci. 111:585-595. Norrander, J.M., Perrone, C.A., Amos, L.A., & Linck, R.W. (1996) Structural comparison of tektins and evidence for their determination of complex spacings in flagellar microtubules. J. Mol. Biol. 257, 385-397. Norrander, J.M., Linck, R.W., & Stephens, R.E. (1995) Transcriptional control of tektin A mRNA correlates with cilia development and length determination during sea urchin embryogenesis. Develop. 121: 1615-1623. Nojima, D., Linck, R.W., & Egelman, E.H. (1995) At least one of the protofilaments in flagellar microtubules is not composed of tubulin. Current Biology 5: 158-167. Pirner, M.A., & Linck, R.W. (1994) Tektins are heterodimeric polymers in flagellar micro-tubules with axial periodicities matching the tubulin lattice. J. Biol. Chem. 269: 31800-31806. Steffen, W., Fajer, E.A., & Linck, R.W. (1994) Centrosomal components immunologically related to tektins from ciliary and flagellar microtubules. J. Cell Sci. 107: 2095-2105. To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed search menu should say PubMed type Linck RW in the avaliable line back to top |
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