Burghardt Wittig

Burghardt Wittig (born December 3, 1947) is the chairman of the Foundation Institute Molecular Biology and Bioinformatics, a non-profit foundation and a German professor of biochemistry and molecular biology at Freie Universitaet Berlin in Berlin (FUB), Germany [1]. He is known for his research in the fields of chromatin structure and gene regulation, DNA structures induced by torsional strain, signal transduction mediated by G-proteins, DNA- and cell-based vaccines and therapeutic immunomodulation.

Early life

Wittig was born in Celle, Germany, where he attended comprehensive secondary school, the classical “Gymnasium Ernestinum”. He started playing clarinet at the age of twelve and six years later won the clarinet competition of the renowned German classical music award “Jugend musiziert”. At the age of 14, he started rowing and later raced successfully in quads and double sculls. He graduated by the German Abitur in fall 1966, followed by two years of service in the German military. While already attending medical school, he also received training as an engineer specialized in hearing aids, and graduated by the German Gesellenpruefung[1] .

Career[1]

Wittig studied Medicine at Freie Universität Berlin from 1968 to 1975. While he was still studying medicine, he joined laboratories at the Institute for Molecular Biology and Biochemistry (Institut für Molekularbiologie und Biochemie) of the Freie Universitaet Berlin and at the Max Planck Institute for Molecular Genetics, to perform the experimental work for his doctoral thesis. His principal thesis advisor was molecular biologist Hubert Gottschling with influential mentoring by V.A. Erdmann, O. Pongs, H.-J. Risse, H. Tiedemann and H.G. Wittmann. Wittig successfully defended his thesis “Purification and Characterization of the Four Lysine-Specific Transfer Ribonucleic Acids from Chicken Embryos” (Reinigung und Charakterisierung der vier lysinspezifischen Transfer-Ribonukleinsäuren aus Hühnerembryonen) in 1976. He continued at Freie Universitaet Berlin, first as a postdoc (1976-1978) and later as an assistant professor (1978-1987).

Between 1976 and 1986, in addition to his work as a researcher, Wittig attended a variety of physics courses as a visiting student at Freie Universität Berlin (FUB), Technische Universität Berlin (TUB), California Institute of Technology (CalTech) and Massachusetts Institute of Technology (MIT) to widen his scientific horizon. He received no official degree for these classes.

In 1980 Wittig habilitated for “Biochemistry and Molecular Biology” and became formally eligible for a full professorship in Germany.

Wittig was awarded a Heisenberg scholarship of the Deutsche Forschungsgemeinschaft (DFG) in 1982/83 and worked as a fellow of the program until 1989. During this time, he was invited by scholars Edward Trifonov, Weizmann Institute of Science, Rehovot, and the late Koki Horikoshi, Riken Institute (ERATO superbug project).

From 1984 to 1986, by invitation of one of molecular biology’s intellectual leaders, Alexander Rich, the late Sedgwick Professor of Biophysics at the Massachusetts Institute of Technology (MIT), he became a visiting professor at Alex Rich’s lab and also cooperated with Alexander Varshavsky; in Wittig’s own words “entering the most career-shaping times of his life”[2].

In 1987, Freie Universitaet Berlin awarded Wittig an extraordinary professorship (“außerplanmäßige Professur“). He continued to work as a visiting professor at MIT in Alex Rich’s lab until 1989, when he became a full professor (S-C4, tenure) at Freie Universitaet Berlin (FUB) and was awarded the Schering Professorship of FUB. One year later, Wittig was tenured (C4, German Full Professorship) as founding chair and department head of Molecular Biology and Bioinformatics at the Institute for Molecular Biology and Biochemistry (Institut für Molekularbiologie und Biochemie) at Freie Universitaet Berlin.

By political administration and change of Berlin law (Berliner Universitaetsmedizingesetz) his institute became an entity of the fused medical faculties of FUB and Humboldt-Universitaet zu Berlin, now named Charité – Universitaetsmedizin. Wittig was Director of his Institute of Molecular Biology and Bioinformatics until 2010.

In 2010 Wittig returned his institute back to Freie Universitaet Berlin as a non-profit foundation with FUB as the trustee. He served as Chairman of the institute, now named Foundation Institute Molecular Biology and Bioinformatics, until 2017.

Beginning in 1994, Wittig focused his research on the design, development, and clinical proof-of-concept of covalently closed DNA constructs for the treatment of cancer and for DNA-vaccines against infectious diseases. Two classes of DNA-molecules evolved through theoretical and experimental selection processes and became key technologies; MIDGE® for minimalistic, immunogenically defined gene expression, and dSLIM® for DNA-based immunomodulation[3].

To enable the independent transition from basic research to DNA medicines, he founded Mologen AG in 1998. Mologen AG had their IPO at the German stock exchange in the same year[4], to become the first German start up solely financed by the stock market and the first German biotech company to go public in the year of its foundation. Wittig served as CEO (Vorstandsvorsitzender) until the end of 2007, while maintaining his full professorship at FUB in a private-public-partnership.

For his courage and innovative spirits in forming Germany’s first Private-Public-Partnership between Mologen and his academic alma mater, Freie Universitaet Berlin, Wittig was granted the “Entrepreneur of the Year” award in 1999. In 2006 Wittig together with Mologen AG received the “Frost & Sullivan Technology Innovation Award of the Year”.

Wittig has published the results of his research in leading scientific journals, including Cell, Nature, PNAS, and Science.

Selected Publications

  • Wittig B, Reuter S, and Gottschling H (1973). Purification of the four lysine specific transfer ribonucleic acids from chick embryos. Biochim. Biophys. Acta, 331: 221-230
  • Allfrey VG, Arnott S, Bradbury EM, Bayev A, Chambon P, Crick FHC, Felsenfeld G, Mirzabekov AT, Noll M, Stern H, van Holde KE, Wittig B, Zachau HG, and Zweidler A (1976) „The Structure of Chromatin“ in: Organization and expression of chromosomes: Dahlem Konferenzen Life Sciences Research Report, 4; Allfrey AG, Bautz EKF, McCarthy BJ, Schimke RT, Tissieres A (Eds.) pp. 19-27; ISBN 10: 3820012052 / ISBN 13: 9783820012057, Abakon Verlagsgesellschaft, Berlin.
  • Wittig, B; Wittig, S (1979). "A phase relationship associates tRNA structural gene sequences with nucleosome cores". Cell. 18(4): 1173–1183. doi:10.1016/0092-8674(79)90230-7
  • Wittig, B; Wittig, S (1982). "Function of a tRNA gene promoter depends on nucleosome position". Nature. 297(5861): 31–38. doi:10.1038/297031a0.
  • Wittig, B; Dorbic, T; Rich, A (1991). "Transcription is associated with Z-DNA formation in metabolically active, permeabilized mammalian cell nuclei"(PDF). Proc. Natl. Acad. Sci. USA. 88(6): 2259–2263. doi:10.1073/pnas.88.6.2259
  • Kleuss, C; Hescheler, J; Ewel, C; Rosenthal, W; Schultz, G; Wittig, B (1991). "Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents". Nature. 353(6339): 43–48. doi:10.1038/353043a0 PMID 1679199.
  • Kleuss, C; Scherübl, H; Hescheler, J; Schultz, G; Wittig, B (1993). "Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins". Science. 259(832–834): 40. doi:10.1126/science.8094261.
  • Müller, V; Takeya, M; Brendel, S; Wittig, B; Rich, A (1996). "Z-DNA forming sites within the human b-globin gene cluster". Proc. Natl. Acad. Sci. USA. 93(2): 780–784. doi:10.1073/pnas.93.2.780
  • Möller P, Sun Y, Dorbic T, Alijagic S, Makki A, Jurgovsky K, Schroff M, Henz BM, Wittig B, and Schadendorf D (1998). 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. British Journal of Cancer, 77 (11): 1907-1916.
  • Wittig, B; Märten, A; Dorbic, T; Weineck, S; Min, H; Niemitz, S; Trojaneck, B; Flieger, D; Kruopis, S; Albers, A; Löffel, J; Neubauer, A; Albers, P; Müller, S; Sauerbruch, T; Bieber, T; Huhn, D; Schmidt-Wolf, IGH (2001). "Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: A first clinical Phase I/II trial". Human Gene Therapy. 12(3): 267–278. doi:10.1089/10430340150218404
  • López-Fuertes, L; Pérez-Jiménez, E; Vila-Coro, AJ; Sack, F; Moreno, S; Konig, SA; Junghans, C; Wittig, B; Timón, M; Esteban, M (2002). "DNA vaccination with linear minimalistic (MIDGE) vectors confers protection against Leishmania major infection in mice". Vaccine. 21(3–4): 247–57. doi:10.1016/s0264-410x(02)00450-4.
  • Weihrauch, MR; Ansen, S; Jurkiewicz, E; Geisen, C; Xia, Z; Anderson, KS; Gracien, E; Schmidt, M; Wittig, B; Diehl, V; Wolf, J; Bohlen, H; Nadler, LM (2005). "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". Clin Cancer Res. 11(16): 5993–6001. doi:10.1158/1078-0432.CCR-05-0018
  • Kneipp, J; Kneipp, H; Wittig, B; Kneipp, K (2007). "One- and two-photon excited optical ph probing for cells using surface-enhanced Raman and hyper-Raman nanosensors". Nano Lett. 7(9): 2819–23. doi:10.1021/nl071418z
  • Endmann, A; Baden, M; Weisermann, E; Kapp, K; Schroff, M; Kleuss, C; Wittig, B; Juhls, C (2010). "Immune response induced by a linear DNA vector: Influence of dose, formulation and route of injection". Vaccine. 28(21): 3642–9. doi:10.1016/j.vaccine.2010.03.034
  • Kapp K, Kleuss C, Schroff M, Wittig B. (2014)Genuine Immunomodulation With dSLIM. Mol Ther Nucleic Acids: 3, e170; doi: 10.1038/mtna.2014.28
  • Wittig B, Schmidt M, Scheithauer W, Schmoll HJ. (2015)MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside. Crit Rev Oncol Haematol 94(1): 31-44; doi: 10.1016/j.critrevonc.2014.12.002.
  • Volz B, Schmidt M, Heinrich K, Kapp K, Schroff M, Wittig B. (2015) Design and characterization of the tumor vaccine MGN1601, allogeneic fourfold gene-modified vaccine cells combined with a TLR-9 agonist. Mol Ther Oncolytics 3: 15023. doi: 10.1038/mto.2015.23.
  • Zhang, S., & Wittig, B. (2015). Alexander Rich: 1924-2015 Nature Biotechnology, 33(6), 593 https://doi.org/10.1038/nbt.3262
  • Vibholm L, Schleimann MH, Højen JF, Benfield T, Offersen R, Rasmussen K, Olesen R, Dige A, Agnholt J, Grau J, Buzon M, Wittig B, Lichterfeld M, Petersen AM, Deng X, Abdel-Mohsen M, Pillai SK, Rutsaert S, Trypsteen W, De Spiegelaere W, Vandekerchove L, Østergaard L, Rasmussen T, Denton PW, Tolstrup M, Søgaard OS. (2017) Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection. Clin Infect Dis 64(12):1686-1695. doi: 10.1093/cid/cix201
  • Krarup AR, Abdel-Mohsen M, Schleimann MH, Vibholm L, Engen PA, Dige A, Wittig B, Schmidt M, Green SJ, Naqib A, Keshavarzian A, Deng X, Olesen R, Petersen AM, Benfield T, Østergaard L, Rasmussen TA, J Agnholt J, Nyengaard JR, Landay A, Søgaard OS, Pillai SK, Tolstrup M, Denton PW. (2018) The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon. Mucosal Immunol 11(2):449-461. doi: 10.1038/mi.2017.59.

References

  1. 1 2 3 "Burghardt Wittig". www.fu-berlin.de. 2012-06-04. Retrieved 2018-07-09.
  2. ↑ Zhang, Shuguang; Wittig, Burghardt (2015-06-01). "Alexander Rich 1924–2015". Nature Biotechnology. 33 (6): 593–598. doi:10.1038/nbt.3262. ISSN 1087-0156.
  3. ↑ "dSLIMming the immune system". BioCentury. Retrieved 2018-07-09.
  4. ↑ "Biotech & Pharma". Cluster Gesundheitswirtschaft Berlin-Brandenburg (in German). Retrieved 2018-07-09.
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