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The Isolation and Localization of Laminin by Rupert Timpl

      Laminin—a Glycoprotein from Basement Membranes (Timpl, R., Rohde, H., Robey, P. G., Rennard, S. I., Foidart, J. M., and Martin, G. R. (1979) J. Biol. Chem. 254, 9933–9937)
      Rupert Timpl (1936–2003) was widely known for his work on extracellular matrix proteins. As a graduate student Timpl, who already had an impressive list of highly cited publications, led a group of connective tissue immunologists started by Carl Steffen at the Institute for General and Experimental Pathology at the University of Vienna Medical School. In this role, Timpl supervised three postdoctoral fellows. He and his colleagues isolated collagen type I and published several papers on the production and specificity of the first antibodies to extracellular matrix proteins.
      Timpl earned his Ph.D. in chemistry from the University of Graz in 1966, and in 1967 he became an Assistant in the Department of Immunology at the University of Vienna, Austria. In 1969 he moved to Germany to become Head of the Research Group in the Department of Connective Tissue Research at the Max-Planck-Institut for Biochemistry in Martinsried/Munich. Timpl remained at Max-Planck for the rest of his scientific career, eventually becoming Scientific Member and Director of the Department of Protein Chemistry in 1992. Timpl also served as the Executive Director of the Max-Planck-Institut from 1995 to 1997.
      At the Max-Planck-Institut, Timpl continued to study extracellular matrix proteins, focusing on the identification of epitopes of collagenous and non-collagenous extracellular matrix proteins, and became one of the first scientists to apply immunofluorescence to the analysis of normal and fibrotic tissues. For example, he showed that the tissue distribution of procollagen type I differs from that of mature type I collagen and also clarified that type III collagen production precedes that of type I collagen in any type of fibrosis.
      The Journal of Biological Chemistry (JBC) Classic reprinted here is the result of a collaboration between Timpl and George R. Martin in which they delineated basement membranes under normal and pathologic conditions. For their studies, Timpl and Martin used a transplantable mouse tumor, the EHS sarcoma, which produced an extracellular matrix of basement membrane. From the tumor, they extracted type IV collagen and, using antibodies, localized it to the basement membrane of normal tissues (
      • Timpl R.
      • Martin G.R.
      • Bruckner P.
      • Wick G.
      • Wiedemann H.
      Nature of the collagenous protein in a tumor basement membrane.
      ,
      • Timpl R.
      • Martin G.R.
      • Bruckner P.
      ). In this paper, Timpl, Martin, and their colleagues isolated a high molecular weight non-collagenous glycoprotein that was also a major constituent of the tumors. They determined that the protein, which they named laminin, consisted of at least two polypeptide chains joined to each other by disulfide bonds. Using purified antibody against laminin, they showed that the glycoprotein is produced by a variety of cultured cells and is a constituent of the basement membranes of these tissues.
      In addition to his research on collagen and laminin, Timpl performed some unorthodox experiments. These included analyzing the distribution of extracellular matrix proteins in 1500-year-old Peruvian mummies, in tissues of the Tyrolean Iceman (Ötzi), and in 50 million-year-old fossils using immunohistochemical and immunofluorescent methods, thus creating a new scientific discipline, paleoimmunology.
      In recognition of his scientific achievements, Timpl received many honors. These include the 1984 Barbara Robert Medal, the 1991 Max Planck Research Award, the 1997 Wenner-Gren Distinguished Lectureship, and the 1998 Lennox K. Black Award from Thomas Jefferson University in Philadelphia.
      Biographical information Rupert Timpl on was taken from Ref.
      • Wick G.
      Rupert Timpl—a Personal Account.
      .
      1Biographical information Rupert Timpl on was taken from Ref.
      • Wick G.
      Rupert Timpl—a Personal Account.
      .
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      Rupert Timpl. Photo reprinted from Ref.
      • Wick G.
      Rupert Timpl—a Personal Account.
      , published by S. Karger AG, Basel.
      Timpl's collaborator on the Classic, George R. Martin, is known for his studies on the structure and function of connective tissue and alterations with disease. At the time the paper was written, Martin was chief of the National Institute of Dental Research's Laboratory of Developmental Biology and Anomalies. In 1988 he was named Scientific Director of the National Institute on Aging, a position he held until 1994. Martin has been involved in two biotech startups, including the South San Francisco-based FibroGen.
      Martin received his undergraduate degree in chemistry from Colgate University and his Ph.D. from the University of Rochester. He has been the recipient of several honors including the International Association of Dental Research Award in Basic Science, the Department of Health and Human Services Distinguished Service Award, the Alexander von Humboldt Senior Scientist Award, and the Federal Meritorious Executive Rank Award in 1987.

      References

        • Timpl R.
        • Martin G.R.
        • Bruckner P.
        • Wick G.
        • Wiedemann H.
        Nature of the collagenous protein in a tumor basement membrane.
        Eur. J. Biochem. 1978; 84: 43-52
        • Timpl R.
        • Martin G.R.
        • Bruckner P.
        Frontiers in Matrix Biology. 7. Karger, Basel1979: 130-141
        • Wick G.
        Rupert Timpl—a Personal Account.
        Int. Arch. Allergy Immunol. 2004; 134: 89-92