Burghardt Wittig

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Burghardt Wittig (* 1947 in Celle , Germany ) is the chairman of the non-profit foundation MolBio²Math - Molecular Biology & Integral Biomathics and a German professor of molecular biology and biochemistry at the Free University of Berlin , Germany. He is known for his research on gene regulation through chromatin structures and on G-protein- dependent signal transduction, as well as for his development of DNA and cell-based vaccinations and therapeutic immunomodulators .

Early life

Wittig was born in Celle, Germany, and attended the Ernestinum high school there. He started playing the clarinet at the age of twelve and six years later won a prize for clarinet in the Jugend musiziert competition . He started rowing at the age of 14 and successfully competed in four and two-two races. In 1966 he passed his Abitur and then completed two years of military service . During his medical studies at the Free University of Berlin, he also completed training as a hearing aid acoustician in his parents' company, which he successfully completed with the journeyman's examination.

Career

From 1968 to 1975 Wittig studied medicine at the Free University of Berlin . During his studies, he worked in the laboratories of the Institute for Molecular Biology and Biochemistry at the Free University and the Max Planck Institute for Molecular Genetics on the experiments for his doctorate.

The molecular biologist Hubert Gottschling was the initiator and main supervisor of this work, but also a pioneer in early scientific life . Important mentors were VA Erdmann , O. Pongs, H.-J, Risse, H. Tiedemann and HG Wittmann. Wittig was able to successfully defend his dissertation with the title “Purification and characterization of the four lysine-specific transfer ribonucleic acids from chicken embryos” in 1976. He continued to work at the Free University, first as a postdoctoral fellow from 1976 to 1978 and then from 1978 to 1987 as an assistant professor .

Between 1976 and 1986 Wittig attended lectures and seminars in physics at the Free University of Berlin (FUB), the Technical University of Berlin (TUB), the California Institute of Technology (CalTech) and the Massachusetts Institute of Technology (MIT). He did not receive a degree for these courses.

In 1980 , Wittig completed his habilitation in biochemistry and molecular biology at the FUB institute of the same name.

In 1982/83 he was awarded the Heisenberg grant from the German Research Foundation (DFG). He was a member of the program until 1989. During this time he received invitations from Edward Trifonov to the Weizman Institute of Science , Israel and - mediated by Hubert Gottschling - from Koki Horikoshi (ERATO suberbug project) to the Riken Institute , Japan.

At the invitation of Alexander Rich , William Thompson Sedgwick Professor of Biophysics at the Massachusetts Institute of Technology - one of the most creative and scientifically influential personalities in the life sciences - Wittig worked as a visiting professor in his laboratory; often accompanied by employees, doctoral students and postdocs of his working group at the FUB. In addition, he cooperated with Alexander Varshavsky . Wittig later described these years as "the most powerful career-shaping period" of his life.

In 1987 FUB Wittig awarded an extraordinary professorship. He continued to work in Alexander Rich's laboratory until he accepted a full professorship at Freie Universität in 1989. The appointment was initially made via the newly created Schering Professorship (S-C4) until he was accepted into the university professorship (C4) a year later . He is the founding board member and head of the department for molecular biology and bioinformatics at the Institute for Molecular Biology and Biochemistry at the Free University.

To enable a better transition from basic research to clinical application, Wittig founded Mologen AG in 1989 . Mologen AG shares were traded on the stock exchange for the first time on June 22, 1989 (IPO). This made Mologen the first German start-up to be financed purely through the stock market and at the same time the first German biotechnology company to go public in the year it was founded.

From 1994 Wittig's research focused on the design, development and clinical testing of DNA-based vaccines against infectious diseases and DNA constructs for the treatment of cancer . Two classes of DNA molecules emerged from these investigations as key technologies: MIDGE® (minimalistic, immunogenically defined gene expression) and dSLIM® (DNA-based immunomodulation).

In 1999, Wittig received the “ Entrepreneur of the Year ” award as an award for his courage and innovative spirit in designing the first German public-private partnership between Mologen AG and his academic alma mater, the Free University of Berlin . In 2006, Wittig and Mologen AG received the “Frost & Sullivan Technology Innovation Award of the Year”.

Wittig worked as CEO of the company until the end of 2007 and retained his full university professorship at Freie Universität as part of a public-private partnership .

As part of the changes in the Berlin University Medicine Act to redesign the university clinics and medical faculties in Berlin, Wittig's Institute became part of the medical faculties of the Humboldt University of Berlin and the Free University of Berlin, which were merged under the name Charité - Universitätsmedizin Berlin . He remained director of the Institute for Molecular Biology and Bioinformatics until 2010.

In 2010 the institute returned to the FUB as the Foundation Institute Molecular Biology and Bioinformatics , a non-profit foundation of the Mologen AG and the Free University of Berlin. Wittig was director of the institute until 2017.

At the end of 2019 he founded the non-profit foundation institute MolBio²Math - Molecular Biology & Integral Biomathics under the trusteeship of the genetic engineering foundation - Dr. Georg and Ingeburg Scheel Foundation.

Selected publications

  • B. Wittig, S. Reuter, H. Gottschling: Purification of the four lysine specific transfer ribonucleic acids from chick embryos. In: Biochim. Biophys. Acta. 331, 1973, pp. 221-230.
  • VG Allfrey, S. Arnott, EM Bradbury, A. Bayev, P. Chambon, FHC Crick, G. Felsenfeld, AT Mirzabekov, M. Noll, H. Stern, KE van Holde, B. Wittig, HG Zachau, A. Zweidler : The Structure of Chromatin. In: AG Allfrey, EKF Bautz, BJ McCarthy, RT Schimke, A. Tissieres (eds.): Organization and expression of chromosomes. (= Dahlem Conferences Life Sciences Research Report. 4). Abakon Verlagsgesellschaft, Berlin 1976, ISBN 3-8200-1205-2 , pp. 19-27.
  • B. Wittig, S. Wittig: A phase relationship associates tRNA structural gene sequences with nucleosome cores. In: Cell. 18 (4), 1979, pp. 1173-1183. doi: 10.1016 / 0092-8674 (79) 90230-7
  • B. Wittig, S. Wittig: Function of a tRNA gene promoter depends on nucleosome position. In: Nature. 297 (5861): 1982, pp. 31-38. doi: 10.1038 / 297031a0 .
  • B. Wittig, T. Dorbic, A. Rich: Transcription is associated with Z-DNA formation in metabolically active, permeabilized mammalian cell nuclei. (PDF). In: Proc. Natl. Acad. Sci. UNITED STATES. 88 (6), 1991, pp. 2259-2263. doi: 10.1073 / pnas.88.6.2259
  • C. Kleuss, J. Hescheler, C. Ewel, W. Rosenthal, G. Schultz, B. Wittig: Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. In: Nature. 353 (6339), 1991, pp. 43-48. doi: 10.1038 / 353043a0 . PMID 1679199
  • C. Kleuss, H. Scherübl, J. Hescheler, G. Schultz, B. Wittig: Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins . Science. 259 (832-834), 1993, p. 40. doi: 10.1073 / pnas.93.2.780 .
  • V. Müller, M. Takeya, S. Brendel, B. Wittig, A. Rich: Z-DNA forming sites within the human b-globin gene cluster. In: Proc. Natl. Acad. Sci. UNITED STATES. 93 (2), 1996, pp. 780-784. doi: 10.1073 / pnas.93.2.780
  • P. Möller, Y. Sun, T. Dorbic, S. Alijagic, A. Makki, K. Jurgovsky, M. Schroff, BM Henz, B. Wittig, D. Schadendorf: Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the anti-melanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study. In: British Journal of Cancer. 77 (11), 1998, pp. 1907-1916.
  • B. Wittig, A. Märten, T. Dorbic, S. Weineck, H. Min, S. Niemitz, B. Trojaneck, D. Flieger, S. Kruopis, A. Albers, J.aken, A. Neubauer, P. Albers, S. Müller, T. Sauerbruch, T. Bieber, D. Huhn, IGH Schmidt-Wolf: Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: A first clinical phase I / II trial. In: Human Gene Therapy. 12 (3), 2001, pp. 267-278. doi: 10.1089 / 10430340150218404
  • L. López-Fuertes, E. Pérez-Jiménez, AJ Vila-Coro, F. Sack, S. Moreno, SA Konig, C. Junghans, B. Wittig, M. Timón, M. Esteban: DNA vaccination with linear minimalistic ( MIDGE) vectors confers protection against Leishmania major infection in mice. In: Vaccine. 21 (3-4), 2002, pp. 247-257. doi: 10.1016 / s0264-410x (02) 00450-4 .
  • MR Weihrauch, S. Ansen, E. Jurkiewicz, C. Geisen, Z. Xia, KS Anderson, E. Gracien, M. Schmidt, B. Wittig, V. Diehl, J. Wolf, H. Bohlen, LM Nadler: Phase I / II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. In: Clin Cancer Res. 11 (16), 2005, pp. 5993-6001. doi: 10.1158 / 1078-0432.ccr-05-0018
  • J. Kneipp, H. Kneipp, B. Wittig, K. Kneipp: One- and two-photon excited optical ph probing for cells using surface-enhanced Raman and hyper-Raman nanosensors. In: Nano Lett. 7 (9), 2007, pp. 2819-2823. doi: 10.1021 / nl071418z
  • A. Endmann, M. Baden, E. Weisermann, K. Kapp, M. Schroff, C. Kleuss, B. Wittig, C. Juhls: Immune response induced by a linear DNA vector: Influence of dose, formulation and route of injection . In: Vaccine. 28 (21), 2010, pp. 3642-3649. doi: 10.1016 / j.vaccine.2010.03.034
  • K. Kapp, C. Kleuss, M. Schroff, B. Wittig: Genuine Immunomodulation With dSLIM. In: Mol Ther Nucleic Acids. 3, 2014, p. E170; doi: 10.1038 / month 2014.28
  • B. Wittig, M. Schmidt, W. Scheithauer, HJ Schmoll: MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside. In: Crit Rev Oncol Haematol. 94 (1), 2015, pp. 31-44. doi: 10.1016 / j.critrevonc.2014.12.002 .
  • B. Volz, M. Schmidt, K. Heinrich, K. Kapp, M. Schroff, B. Wittig: Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist. In: Mol Ther Oncolytics. 3, 2015, p. 15023. doi: 10.1038 / mto.2015.23 .
  • S. Zhang, B. Wittig: Alexander Rich: 1924-2015. In: Nature Biotechnology. 33 (6), 2015, p. 593. doi: 10.1038 / nbt.3262
  • L. Vibholm, MH Schleimann, JF Højen, T. Benfield, R. Offersen, K. Rasmussen, R. Olesen, A. Dige, J. Agnholt, J. Grau, M. Buzon, B. Wittig, M. Lichterfeld, AM Petersen, X. Deng, M. Abdel-Mohsen, SK Pillai, S. Rutsaert, W. Trypsteen, W. De Spiegelaere, L. Vandekerckhove, L. Østergaard, T. Rasmussen, PW Denton, M. Tolstrup, OS Søgaard : Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection. In: Clin Infect Dis. 64 (12), 2017, pp. 1686–1695. doi: 10.1093 / cid / cix201
  • AR Krarup, M. Abdel-Mohsen, MH Schleimann, L. Vibholm, PA Engen, A. Dige, B. Wittig, M. Schmidt, SJ Green, A. Naqib, A. Keshavarzian, X. Deng, R. Olesen, AM Petersen, T. Benfield, L. Østergaard, TA Rasmussen, J. Agnholt, JR Nyengaard, A. Landay, OS Søgaard, SK Pillai, M. Tolstrup, PW Denton: The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon. In: Mucosal Immunol. 11 (2), 2018, pp. 449-461. doi: 10.1038 / mi.2017.59 .
  • Thomas M, Ponce-Aix S, Navarro A, Riera-Knorrenschild J, Schmidt M, Wiegert E, Kapp K, Wittig B, Mauri C, Dómine Gómez M, Kollmeier J, Sadjadian P, Fröhling KP, Huber RM, Wolf M, for the IMPULSE study team. (2018) Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study. Annals of Oncology 29 (10): 2076-2084. doi: 10.1093 / annonc / mdy326
  • Kapp K, Volz B, Oswald D, Wittig B, Baumann M, Schmidt M. (2019) Beneficial modulation of the tumor microenvironment and generation of anti-tumor responses by TLR9 agonist lefitolimod alone and in combination with checkpoint inhibitors. OncoImmunology. doi: 10.1080 / 2162402X.2019.1659096 .
  • Schleimann MH, Kobberø ML, Vibholm LK, Kjær K, Giron LB, Busman-Sahay K, Chan CN, Nekorchuk M, Schmidt M, Wittig B, Damsgaard TE, Ahlburg P, Hellfritzsch MB, Zuwala K, Rothemejer FH, Olesen R, Schommers P, Klein F, Dweep H, Kossenkov A, Nyengaard JR, Estes JD, Abdel-Mohsen M, Østergaard L, Tolstrup M, Søgaard OS, Denton PW. (2019) TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes. EBioMedicine. doi: 10.1016 / j.ebiom.2019.07.005 .   
  • Schmidt M, Schroff M, Wittig B (2020) "Harnessing the Therapeutic Potential of Dendritic Cells" in: Second Generation Cell and Gene-based Therapies, pp. 183-202; Alain A. Vertès, Devyn M. Smith, Nasib Qureshi, Nathan J. Dowden (Eds.) ISBN 978-0-12-812034-7 , Academic Press, London

Web links

Individual evidence

  1. - Researchers - Molecular Biology & Integral Biomathics. Retrieved March 25, 2020 .
  2. a b c d Burghardt Wittig. June 4, 2012, accessed October 10, 2018 .
  3. Shuguang Zhang, Burghardt Wittig: Alexander Rich 1924-2015 . In: Nature Biotechnology . tape 33 , no. June 6 , 2015, ISSN  1087-0156 , p. 593-598 , doi : 10.1038 / nbt.3262 .
  4. Dslimming the immune system to www.biocentury.com