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On the road from classical to modern molecular biology

Nature Medicine volume 18, pages 1499–1502 (2012)Cite this article

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I graduated from the University of Colorado in Boulder in 1965, and, while browsing through the university bookstore, I noticed a new book called Molecular Biology of the Gene by James Watson. When I read it, I was captivated by the elegance and power of an exciting new field that combined structure, genetics and biochemistry. Delving more deeply, I was fascinated by the classic paper of Francois Jacob and Jacque Monod on the operon theory and the subsequent identification of the Lac and λ phage repressors by Walter Gilbert and Mark Ptashne, respectively. These breakthroughs in our understanding of gene regulation in prokaryotes, which were based on a combination of ingenuity, genetics and biochemistry, defined classical molecular biology and inspired me to seek a PhD in the new field and, ultimately, to study the mechanisms of gene regulation in eukaryotes.

On the basis of my interest in molecular biology, Joseph Daniel, my undergraduate research advisor at Colorado, suggested that I contact Leonard Lerman, who had recently moved from the University of Colorado Medical School to the new Department of Molecular Biology at Vanderbilt University. I took Joe's advice and ultimately joined Leonard's lab, where I studied the structure of highly compacted DNA by small-angle X-ray scattering. Leonard was an excellent mentor who encouraged critical thinking, and I enjoyed learning a new field. Toward the end of my thesis research, Mark Ptashne visited Vanderbilt, and during his dinner with the graduate students I had the opportunity to discuss my interests in his work. That conversation ultimately led to an offer to join Mark's lab at Harvard for postdoctoral studies.

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Figure 1: Photos of me and my colleagues taken circa 1976–1978.
Figure 2: Schematic illustrating the synthesis and cloning of double-stranded cDNA from purified rabbit β-globin mRNA using the sequential activities of reverse transcriptase and DNA polymerase I.
Figure 3: Schematic illustrating our strategy for the construction of a genomic DNA library.

References

  1. Maniatis, T. in Life Illuminated: Selected Papers from Cold Spring Harbor, Volume 2 (1972–1994). (eds. Witkowski, J., Gann, A. and Sambrook, J.) 227 (Cold Spring Harbor Press, 2008).

    Google Scholar 

  2. Maniatis, T., Sim, G.K., Efstratiadis, A. & Kafatos, F.C. Amplification and characterization of a β-globin gene synthesized in vitro. Cell 8, 163–182 (1976).

    Article  CAS  Google Scholar 

  3. Maniatis, T. et al. The isolation of structural genes from libraries of eukaryotic DNA. Cell 15, 687–701 (1978).

    Article  CAS  Google Scholar 

  4. Fritsch, E.F., Lawn, R.M. & Maniatis, T. Molecular cloning and characterization of the human β-like globin gene cluster. Cell 19, 959–972 (1980).

    Article  CAS  Google Scholar 

  5. Treisman, R., Orkin, S.H. & Maniatis, T. Specific transcription and RNA splicing defects in five cloned β-thalassemia genes. Nature 302, 591–596 (1983).

    Article  CAS  Google Scholar 

  6. Mellon, P., Parker, V., Gluzman, Y. & Maniatis, T. Identification of DNA sequences required for transcription of the human α1-globin gene in a new SV40 host-vector system. Cell 27, 279–288 (1981).

    Article  CAS  Google Scholar 

  7. Wold, B. et al. Introduction and expression of a rabbit β-globin gene in mouse fibroblasts. Proc. Natl. Acad. Sci. USA 76, 5684–5688 (1979).

    Article  CAS  Google Scholar 

  8. Maniatis, T., Fritsch, E.F. & Sambrook, J. Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor Press, 1982).

    Google Scholar 

  9. Krainer, A.R., Maniatis, T., Ruskin, B. & Green, M.R. Normal and mutant human β-globin pre-mRNAs are faithfully and efficiently spliced in vitro. Cell 36, 993–1005 (1984).

    Article  CAS  Google Scholar 

  10. Ruskin, B., Krainer, A.R., Maniatis, T. & Green, M.R. Excision of an intact intron as a novel lariat structure during pre-mRNA splicing in vitro. Cell 38, 317–331 (1984).

    Article  CAS  Google Scholar 

  11. Fu, X.-D. & Maniatis, T. Isolation of a complementary DNA that encodes the mammalian splicing factor SC35. Science 256, 535–538 (1992).

    Article  CAS  Google Scholar 

  12. Reed, R. & Maniatis, T. A role for exon sequences and splice-site proximity in splice-site selection. Cell 46, 681–690 (1986).

    Article  CAS  Google Scholar 

  13. Tian, M. & Maniatis, T. A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Cell 74, 105–114 (1993).

    Article  CAS  Google Scholar 

  14. Thanos, D. & Maniatis, T. Virus induction of human IFN-γ gene expression requires the assembly of an enhanceosome. Cell 83, 1091–1100 (1995).

    Article  CAS  Google Scholar 

  15. Fan, C.-M. & Maniatis, T. Generation of p50 subunit of NF-κB by processing of p105 through an ATP-dependent pathway. Nature 354, 395–398 (1991).

    Article  CAS  Google Scholar 

  16. Palombella, V.J., Rando, O.J., Goldberg, A.L. & Maniatis, T. The ubiquitin/proteasome pathway is required for processing the NFkB1 precursor protein and the activation of NFκB. Cell 78, 773–785 (1994).

    Article  CAS  Google Scholar 

  17. Chen, Z.J., Parent, L. & Maniatis, T. Site-specific phosphorylation of IκBα by a novel ubiquitination-dependent protein kinase activity. Cell 84, 853–862 (1996).

    Article  CAS  Google Scholar 

  18. Sánchez-Serrano I. Success in translational research: lessons from the development of bortezomib. Nat. Rev. Drug Discov. 5, 107–114 (2007).

    Article  Google Scholar 

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  1. Tom Maniatis is in the Department of Biochemistry & Biophysics, Columbia University, New York, New York, USA.,

    Tom Maniatis

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  1. Tom Maniatis
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Correspondence to Tom Maniatis.

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Competing interests

T.M. receives royalty payments on the sale of bortezomid as a scientific founder of ProScript and as an inventor on US patent number 6660268, entitled “Proteasome regulation of NF-κB activity.”

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Maniatis, T. On the road from classical to modern molecular biology. Nat Med 18, 1499–1502 (2012). https://doi.org/10.1038/nm.2931

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