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Back to the future: education for systems-level biologists


We describe a graduate course in quantitative biology that is based on original path-breaking papers in diverse areas of biology; each of these papers depends on quantitative reasoning and theory as well as experiment. Close reading and discussion of these papers allows students with backgrounds in physics, computational sciences or biology to learn essential ideas and to communicate in the languages of disciplines other than their own.

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  1. Bialek, W. & Botstein, D. Introductory science and mathematics education for 21st century biologists. Science 303, 788–790 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Luria, S. E. & Delbrück, M. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28, 491–511 (1943).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Elowitz, M. B., Levine, A. J., Siggia, E. D. & Swain, P. S. Stochastic gene expression in a single cell. Science 297, 1183–1186 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Novick, A. & Wiener, M. Enzyme Induction as an all-or-none phenomenon. Proc. Natl Acad. Sci. USA 43, 553–566 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dekel, E. & Alon, U. Optimality and evolutionary tuning of the expression level of a protein. Nature 436, 588–592 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Barkai, N. & Leibler, S. Robustness in simple biochemical networks. Nature 387, 913–917 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Goldbeter, A. & Koshland, D. E. Jr. An amplified sensitivity arising from covalent modification in biological systems. Proc. Natl Acad. Sci. USA 78, 6840–6844 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hopfield, J. J. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc. Natl Acad. Sci. USA 71, 4135–4139 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Smith, T. F. & Waterman, M. S. Identification of common molecular subsequences. J. Mol. Biol. 147, 195–197 (1981).

    Article  CAS  PubMed  Google Scholar 

  10. Felsenstein, J. Evolutionary trees from DNA sequences: a maximum likelihood approach. J. Mol. Evol. 17, 368–376 (1981).

    Article  CAS  PubMed  Google Scholar 

  11. Eisen, J. A. A phylogenomic study of the MutS family of proteins. Nucleic Acids Res. 26, 4291–4300 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Eisen, M. B., Spellman, P. T., Brown, P. O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA 95, 14863–14868 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hodgkin, A. L. Croonian Lecture, ionic movements and electrical activity in giant nerve fibres. Proc. R. Soc. Lond. B. Biol. Sci. 148, 1–37 (1958).

    Article  CAS  PubMed  Google Scholar 

  14. Ozbudak, E. M., Thattai, M., Lim, H. N., Shraiman, B. I. & Van Oudenaarden A. Multistability in the lactose utilization network of Escherichia coli. Nature 427, 737–740 (2004).

    Article  CAS  PubMed  Google Scholar 

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Correspondence to David Botstein.

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Croonian Lecture

The Croonian Lectures are prestigious lectureships given at the invitation of the Royal Society and the Royal College of Physicians.

Diauxic growth

In a medium that contains glucose and a less preferred carbon source, bacteria exhaust the glucose before consuming the other carbon source. Monod called this behaviour diauxie ('double growth' in French).

Hodgkin–Huxley equations

Hodgkin and Huxley published a series of (now classic) papers in 1952 on electrical activity and transmembrane ion currents in the squid giant axon. In these papers, they derived the Hodgkin–Huxley equations, which accurately describe the action potential.


In a series of parallel cultures, the Luria–Delbrück 'jackpot' is the rare observation of a large clone of mutant cells that are derived from a single mutational event early in the growth of the culture. Though rare, these jackpots occur much more frequently than the probability p(n) that is expected from simple Poisson statistics.

Poisson distribution

This distribution, p(n) = exp(-λ)λn/n!, gives the probability of observing n rare random events in a very large population, for which λ is the average expected number of these rare events.

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Wingreen, N., Botstein, D. Back to the future: education for systems-level biologists. Nat Rev Mol Cell Biol 7, 829–832 (2006).

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