9.53 Cellular and Molecular Computation

Lecture schedule

• Tu 2/1 
  • Introduction and overview.  The problem of understanding nonlinearity and feedback in biological networks. 
  • RNA world.  Directed molecular evolution and SELEX
  • MBOC, Chapter 1, pp. 4-11.  Section: From molecules to the first cell.
  • MBOC, Chapter 6, pp. 273-8.  Section: Viruses, plasmids, and transposable genetic elements.
  • S. Spiegelman.  An approach to the experimental analysis of precellular evolution. Q. Rev. Biophys. 4:213-53 (1971).
  • L. Gold et al.  From oligonucleotide shapes to genomic SELEX: Novel biological regulatory loops.  Proc. Natl. Acad. Sci. USA 94:59-64 (1997).
• Th 2/3
  • DNA computing and self-assembly
  • L. M. Adleman.  Molecular computation of solutions to combinatorial problems. Science 1994 Nov 11;266(5187):1021-4.
  • Winfree E, Liu F, Wenzler LA, Seeman NC.  Design and self-assembly of two-dimensional DNA crystals.  Nature 1998 Aug 6;394(6693):539-44.
• Tu 2/8
  • Enzyme kinetics.  Michaelis-Menten theory.  Cooperative behavior.
  • Stryer, pp. 192-9.
  • Heinrich and Schuster, pp. 16-24.
• Th 2/10
  • Metabolic control analysis. 
  • D. A. Fell.  Metabolic control analysis: a survey of its theoretical and experimental development.  Biochem. J. 286:313-30 (1992).
  • Heinrich and Schuster, pp. 160-2.
• Tu 2/15
  • General formalism for chemical reaction networks.  Metabolic flux analysis.
  • Heinrich and Schuster, pp. 9-15.
• Th 2/17
  • Student presentations (Andrew and Divakar): Theory of chemical computation
  • M. O. Magnasco.  Chemical kinetics is Turing universal.   Phys. Rev. Lett. 78:1190-3 (1997).
  • Problem Set #1 distributed
• Th 2/24
  • Overview of transcriptional regulation.  Lambda phage.
  • MBOC, Chapter 6, pp. 223-7.  Chapter 8, pp. 365-71.  Chapter 9, pp. 401-453.
  • Problem Set #1 due!
• Tu 2/29
  • Models of bistability in chemical reaction networks.
  • Additional reading:
• Th 3/2
  • Demo of Bard Ermentrout's XPP.   Chemical reaction networks versus neural networks.  Global stability of symmetric networks.
• Tu 3/7
  • Student presentations (Justin and Ila): Synthetic genetic networks
  • T. S. Gardner, C. R. Cantor, and J. J. Collins. Construction of a genetic toggle switch in Escherichia coli.  Nature 403:339-342 (2000).
  • M. Elowitz and S. Leibler.  A synthetic oscillatory network of transcriptional regulators.  Nature 403:335-338 (2000).
  • Additional reading:  R. Lutz and H. Bujard.  Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements.  Nucleic Acids Res. 25:1203-10 (1997).
• Th 3/9
  • Oscillations in an activator-inhibitor system.  Phase plane analysis.
  • Additional reading (on reserve in MIT Libraries): S. Strogatz. Nonlinear dynamics and chaos.  L. Edelstein-Keshet. Mathematical models in biology.
  • Stochastic simulations of chemical reactions
  • Additional reading: D. T. Gillespie.  Exact stochastic simulation of coupled chemical reactions.  J. Phys. Chem. 81:2341-61 (1977).
• Tu 3/14
  • Hodgkin-Huxley model of the action potential.
  • C. Koch.  Biophysics of Computation.  Chapter 6.
• Th 3/16 Problem Set #2 distributed
  • Spike frequency adaptation and negative feedback linearization.
  • B. Ermentrout.  Linearization of F-I curves by adaptation.   Neural Comput. 10:1721-9 (1998).

  Spring vacation

• Tu 3/28
  • Phototransduction (Philip)
  • R. W. Rodieck.  The first steps in seeing.  Sinauer, 1998.
  • Stryer, Chapter 13.
  • M. Gray-Keller, W. Denk, B. Shraiman, and P. B. Detwiler. Longitudinal spread of second messenger signals in isolated rod outer segments of lizards. J. Physiol. 519.3:679-92 (1999).
  • P. Detwiler, S. Ramanathan, A. Sengupta, and B. I. Shraiman.  Engineering aspects of enzymatic signal transduction: photo-receptors in the retina.  preprint.
• Th 3/30
  • Chemotaxis (Mike and Vishal)
  • Stryer, Chapter 13
  • H. C. Berg.  Random walks in biology.  Princeton, 1983.
  • D. Bray, R. B. Bourret, and M. I. Simon.  Computer simulation of the phosphorylation cascade controlling bacterial chemotaxis.  Mol. Biol. Cell. 4:469-82 (1993).
  • N. Barkai and S. Leibler.  Robustness in simple biochemical networks.  Nature 387:913-7 (1997).
  • U. Alon, M. G. Surette, N. Barkai, and S. Leibler.  Robustness in bacterial chemotaxis.  Nature 397:168-71 (1999).
  • D. Bray, M. D. Levin, and C. J. Morton-Firth.  Receptor clustering as a cellular mechanism to control sensitivity.  Nature 393:85-8 (1998).
• Tu 4/4  Problem 1 of Assignment 2 due!
  • Long-term potentiation (Joe and Andrew)
  • Required:
    R. C. Malenka and R. A. Nicoll. Long-term potentiation---a decade of progress? Science 285:1870-74 (1999).
    J. Dubnau and T. Tully. Gene discovery in Drosophila: new insights for learning and memory. Annu. Rev. Neurosci. 21:407-44 (1998).
  • Recommended:
    J. Lisman.  A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase.  Proc. Natl. Acad. Sci. USA 82:3055-7 (1985).
    J. Lisman and M. A. Goldring.  Feasibility of long-term storage of graded information by the Ca2+/calmodulin-dependent protein kinase molecules of the postsynaptic density.  Proc. Natl. Acad. Sci. USA 85:5320-4 (1988)
    J. Lisman.  A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory.  Proc. Natl. Acad. Sci. USA.  86:9574-78 (1989).
    J. Lisman. The CaM kinase II hypothesis for the storage of synaptic memory.   Trends Neurosci. 17:406-12 (1994).
  • Additional:
    Squire and Kandel.  Memory: from mind to molecules.  Chapter 7.   Scientific American Library, 1999.
    U. S. Bhalla and R. Iyengar.  Emergent properties of networks of biological signaling pathways.  Science 283:381-7 (1999).
• Th 4/6
  • no class
• Tu 4/11
  • Circadian rhythms (Derek and Justin C.)
  • J. C. Dunlap.  Molecular bases for circadian clocks. Cell 96:271-90 (1999).
  • Tyson et al. A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM. Biophys J. 77:2411-7 (1999).
  • Johnson and Golden, Circadian Programs in Cyanobacteria: Adaptiveness and Mechanism, Annu. Rev. Microbiol. 53:389-409 (1999).
  • N. Barkai and S. Leibler. Circadian clocks limited by noise. Nature 403:267-8 (2000).
  • N. R. J. Glossop, L. C. Lyons, and P. E. Hardin. Interlocked feedback loops within the Drosophila circadian oscillator. Science 286:766-8 (1999).
• Th 4/13
  • Stochastic models of lambda phage (Mukund)
  • H. H. McAdams and A. Arkin. Stochastic mechanisms in gene expression. Proc. Natl. Acad. Sci. USA 94:814-9 (1997).
  • M. A. Gibson and J. Bruck. A probabilistic model of a prokaryotic gene and its regulation. In Computational Methods in Molecular Biology: From Genotype to Phenotype. Eds. Bolouri and Bower (in press).
  • A. Arkin, J. Ross, and H. H. McAdams. Stochastic kinetic analysis of developmental pathway bifurcation in phage l-infected Escherichia coli cells. Genetics 149:1633-48 (1998).
• Th 4/20
  • Molecular motors (Divakar and Sebastian)
  • J. Howard. Molecular motors: structural adaptations to cellular functions. Nature 389: 561-6 (1997).
  • A. D. Mehta, M. Rief, J. A. Spudich, D. A. Smith, and R. M. Simmons. Single-molecule biomechanics with optical methods. Science 283:1689-95 (1999).
• Tu 4/25
  • Development (Miriam and Justin C.)
  • J. Reinitz, D. Kosman, C. E. Vanario-Alonso, and D. H. Sharp.  Stripe forming architecture of the gap gene system.  Dev. Genetics 23:11-27 (1998).
  • L. Wolpert. Positional Information and Pattern Formation in Development. Dev. Genetics 15:485-490 (1994).
  • D. Stanojevic, S. Small, and M. Levine. Regulation of a Segmentation Stripe by Overlapping Activators and Repressors in the Drosophilia Embryo. Science 254:1385-1387 (1991).
  • Additional reading: P. A. Lawrence. The making of a fly: the genetics of animal design. Blackwell (1992).
• Th 4/27
  • Cell cycle (Mike and Joan)
  • MBOC, Chapter 17.
  • A. Goldbeter. A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase. Proc. Natl. Acad. Sci. USA 88:9107-9111 (1991).
  • B. Novak and J. J. Tyson. Modeling the control of DNA replication in fission yeast. Proc. Natl. Acad. Sci. USA 94:9147-52 (1997).
  • T. Gardner, M. Dolnik, and J. J. Collins. A theory for controlling cell cycle dynamics using a reversibly binding inhibitor. Proc. Natl. Acad. Sci. USA 95:14190-95 (1998).
• Tu 5/2
  • Pattern formation and slime molds (Derek and Joe)
  • D. A. Kessler and H. Levine. Pattern formation in Dictyostelium via the dynamics of cooperative biological entities. Phys. Rev. E48:4801-4 (1993).
  • H. Levine, I. Aranson, L. Tsimring, and T. V. Truong. Positive genetic feedback governs cAMP spiral wave formation in Dictyostelium. Proc. Natl. Acad. Sci. USA 93:6382-6 (1996).
  • The Dictyostelium Virtual Library
• Th 5/4
  • Cell sorting (Justin W. and Mukund)
  • N. Kataoka, K. Saito, and Y. Sawada.  NMR microimaging of the cell sorting process. Phys. Rev. Lett. 82:1075 (1999).
  • F. Graner and J. A. Glazier. Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys. Rev. Lett. 69:2013-6 (1992).
  • J. A. Glazier and F. Graner. Simulation of the differential adhesion driven rearrangement of biological cells. Phys. Rev. E47:2128-54 (1993).
  • M. S. Steinberg. Reconstruction of Tissues by Dissociated Cells. Science. 141 No. 3579: 401-408 (1963).
• Tu 5/9
  • Immunity (Ila and Joan)
  • MBOC, Chapter 23.
  • A. V. M. Herz, S. Bonhoeffer, R. M. Anderson, R. M. May, and M. A. Nowak. Viral dynamics in vivo: limitations on estimates of intracellular delay and virus decay. Proc. Natl. Acad. Sci. USA 93:7247-51 (1996).
  • A. S. Perelson and G. Weisbuch. Immunology for physicists.   Rev. Mod. Phys. 69:1219-67 (1998).
  • Xiping Wei et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 373:117-122 (1995).
  • D. D. Ho et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 373:123-126 (1995).
• Th 5/11
  • Final project presentations