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General Information

Required Textbook

Physical Biology of the Cell by Phillips, Kondev and Theriot ISBN: 0815341636

 

Optional Textbooks

	An Introduction to Systems Biology by Uri Alon ISBN: 1584886420
	Chemical Biophysics by Beard and Qian ISBN: 0521870704
	Reading the Story in DNA by Lindell Bromham ISBN: 0521870704

 

 

Syllabus

• 2009 Syllabus (PDF)
  
  

  DATE	TOPIC (click for slides and suggested reading)
  1/13	Intro/Photosynthesis 1
  1/15	Photosynthesis (phenomenology and estimates)
  1/16	Quantum mechanics review
  1/20	Light Harvesting 1	READING: PBoC Chs 2 and 3, Great Ideas of Biology; HW 1 out
  1/22	Light Harvesting 2
  1/27	Electron Transfer	HW 1 due, HW 2 out
  1/29	Light and Biological Clocks
  2/3	Story of Genes, Chromosomes and Genomes	HW 2 due, HW 3 out
  2/5	Genome Packing (chromosome geography and nucleosomes)
  2/10	Gene Regulation 1	HW 4 out
  2/12	Special Lecture (Darwin's birthday!)	HW 3 due
  2/17	NO CLASS--Rob out of town	HW 4 due 5 pm outside Rob's office
  2/19	Time-Dependent Gene Regulation
  2/24	Signalling	HW 5 out (due 3/5)
  2/26	Mechanosensation

 

Readings

1. Light and Life
   
   
• Suggested Reading:
  
  
  • Hangarter and Gest (2004) Pictoral Demonstrations of Photosynthesis. Photosynthesis Res. 80: 421-425
    This article describes some of the historic studies which demonstrated the connection between light and photosynthesis, using clever photography on leaves. This is very similar in spirit to the work in the group of Chris Voigt at UCSF who does similar stuff with bacteria (see next reference below).  These experiments were then turned into a pedagogical tool.
  • Levskaya, A., et al (2005) Engineering E. coli to see light, Nature, 438: 441-442.
  • Rabinowitch and Govindjee, Photosynthesis.
  This book is old, but still extremely interesting and helpful as a source on photosynthesis.


• Lectures 1 and 2 (pptx/ppt/pdf):
  ERRATUM: The stoichiometric equation for photosynthesis was incorrect on the slide shown in class; it's been corrected in these posted versions of the slides.  NB: Lecture 1 was split between Tuesday's and Thursday's class, so the second half of the slides are subject to change! (Modified versions will be posted as necessary.)
  
  Additional reading and useful links for Lectures 1 and 2:
This paper gives a sense of the nature of carboxysomes:
• Cannon G.C., Bradburne C.E., Aldrich H.C., Baker S.H., Heinhorst S., and Shively J.M.  (2001) Microcompartments in prokaryotes: carboxysomes and related polyhedra.  Appl. Environ. Microbiol.  67 (12): 5351-5361.
  
These papers give some beautiful electron microscopy results on the nature of photosynthetic membranes in cyanobacteria:
• van de Meene, A.M.L., Hohmann-Marriott, M.F., Vermaas W.F.J., and Roberson R.W. (2006) The three-dimensional structure of the cyanobacterium Synechocystis sp. PCC 6803.  Arch. Microbiol. 184: 259-270.
• Ting C.S., Hseih C., Sundararaman S., Mannella C., and Marko M. (2007) Cryo-electron tomography reveals the comparative three-dimensional architecture of Prochlorococcus, a globally important marine cyanobacterium.  J. Bacteriol. 189 (12): 4485-4493.
• Liberton M., Berg R.H., Heuser J., Roth R., and Pakrasi H.B. (2006) Ultrastructure of the membrane systems in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803.  Protoplasma 227: 129-138.
  
This paper gives a description of the experimental analysis of the primary productivity due to photosynthesis on the earth:
• Field, C.B., Behrenfeld M.J., Randerson J.T., and Falkowski P. (1998) Primary production of the biosphere: Integrating terrestrial and oceanic components.  Science 281: 237-240.
  
This is an interesting explanation of the Coastal Zone Color Scanner used to take a census of photosynthetic organisms in the ocean:
• http://daac.gsfc.nasa.gov/guides/GSFC/guide/CZCS_Sensor.gd.shtml
This is the essay mentioned in class that argues for the role of evolution as the prism through which biological phenomena are viewed:

• Dobzhansky, T.  (1973) Nothing in biology makes sense except in the light of evolution.  The American Biology Teacher, 125-129.
This paper reports the results of some of the classic Emerson and Arnold experiments in which a flashing light source was used to probe the photosynthetic process:
• Emerson, R. and Arnold, W. (1932) The photochemical reaction in photosynthesis.  J. Gen. Physiol. 16: 191-205.
  This is an article on a similar topic as a lecture (with the same name) given by Paul Nurse, president of Rockefeller University and the 2001 Nobel Laureate in Physiology or Medicine:
• Nurse, P.  (2003) The great ideas of biology.  Clin. Med. 3(6): 560-568.
  The Carl Sagan clip from youtube Rob mentioned:
• Sagan C., Pale Blue Dot.
  This paper gives a description of the physics and chemistry of electron transfer and is the source of several of the slides used in class:
• Gray, H., and Winkler, J. (2005) Long-range electron transfer. PNAS 102 (10): 3534 - 3539.
  This paper gives a description of the electronic structure of porphyrins and will be relevant to our discussion of electron structure in coming lectures:
• Gouterman, M. (1961) Spectra of Porphyrins. Journal of Molecular Spectroscopy 6: 138 - 163.
  This paper uses AFM to examine the molecular structures in photosynthetic membranes:
• Scheuring, S., and Sturgis, J. (2005) Chromatic adaptation of Photosynthetic Membranes. Science 309 (5733): 484 - 487.
  This paper counts the number of Rubisco molecules in each carboxysome and can be used as a basis for thinking about the estimate we performed in class:
• Iancu C.V., Ding H.J., Morris D.M, Dias D.P., Gonzales A.D., Martino A., and Jensen G.J. (2007) The structure of isolated Synechococcus strain WH8102 carboxysomes as revealed by electron cryotomography.  J. Mol. Biol 372: 764-773.
The Wikipedia article on the Wallace line mentioned in class today:
• http://en.wikipedia.org/wiki/Wallace_Line
  An article on the bet mentioned in class today about the number of genes in the human genome:
• http://www.sciencemag.org/cgi/content/full/300/5625/1484b
  
  
• Quantum mechanics review:
• Notes
  The TAs' notes from the review session for those who couldn't make it.
• Excerpt from Crystals, Defects and Microstructures.
  This is an excerpt from Rob's book Crystals, Defects and Microstructures that gives some background on the quantum mechanics topics we'll be studying.
• Feynman Lectures, vol. 3, first three lectures
• http://www.almaden.ibm.com/vis/stm/corral.html
  This website shows how researchers at IBM have assembled 'quantum corrals' where electrons are confined and can be examined using simple ideas from quantum mechanics like those described in class.
  
  
• Lecture 3 (pptx/ppt/pdf)
  
  Additional reading and useful links for Lecture 3:
This website has a variety of pdb coordinates for carbon compounds:
• http://www.nyu.edu/pages/mathmol/library/
  This website has some useful comments on the properties of carbon:
  
• http://www.nyu.edu/pages/mathmol/modules/carbon/carbon1.html
  These three old papers show how simple free electron ideas were used to understand the absorption properties of biological pigments, similar to what we've been doing in class.  Eqn. 2 of the first paper gives a very nice result in particular and the numbers are calculated after that:
• Kuhn, H. (1948) Free electron model for absorption spectra of organic dyes. J. Chem. Phys. 16: 840-841.
• Kuhn, H. (1949)  A quantum-mechanical theory of light absorption of organic dyes and similar compounds.  J. Chem. Phys.  17(12): 1198-1212.
• Simpson, W.T. (1949)  On the theory of the pi-electron system in porphines.  J. Chem. Phys. 17 (12): 1218-1221.
  
  
• Lecture 4 (pptx/ppt/pdf); the chart Rob drew on the board at the beginning of class
  
  Additonal reading for Lecture 4:
• A figure from Daudel, R., Electronic Structure of Molecules, showing the relationship between the free electron model (full lines) and the linear combination of atomic orbitals model (dotted line) for linear chain molecules.  This is a particularly pretty representation of the two limits discussed in class.
  
  
• Lecture 5 (pptx/ppt/pdf)
  
  Additional reading and useful links for Lecture 5:
This classic paper shows how the idea of tunneling can be used to understand radioactive decay:
• Gurney, R.W. and Condon, E.U. (1929) Quantum mechanics and radioactive disintegration.  Phys. Rev. 33 (2): 127-140.
This paper shows how tunneling ideas can be used to understand electron transfer in proteins:
• Hopfield, J.J. (1974) Electron transfer between biological molecules by thermally activated tunneling. PNAS 71 (9):3640-3644.
This interesting review has a description of the measurement of electron tunneling in proteins:
• Gray, H.B. and Winkler, J.R. (2003) Electron tunneling through proteins.  Quart. Rev. Biophys. 36 (3): 341-372.
This excellent short piece gives a status report on electron transfer and provides some of the figures discussed in class (also posted under Lectures 1 and 2):
• Gray, H., and Winkler, J. (2005) Long-range electron transfer. PNAS 102 (10): 3534 - 3539.
This paper describes some of the early measurements on tunneling in proteins that we discussed in class:
• Langen R., Chang I-J., Germanas J.P., Richards J. H., Winkler J.R., and Gray, H.B. (1995) Electron tunneling in proteins: coupling through a beta-strand. Science 268 (5218): 1733-1735.
This website performs calculations of electron transfer rates as a function of distance between donor and acceptor:
• http://www.uphs.upenn.edu/biocbiop/local_pages/dutton_lab.html
  
  
2. Genes: Expression, Regulation and Management


• Lecture 6 (pptx/ppt/pdf)
  
  Additional reading and useful links for Lecture 6: 
This paper shows periodic gene expression in cyanobacteria:

• Mihalcescu I., Hsing W., and Leibler S. (2004) Resilient circadian oscillator revealed in individual cyanobacteria. Nature 430: 81-85.
The latter sections of this article by Martin Raff discuss the amazing Bombyx mori that I mentioned in class:
• Raff M.  Intracellular developmental timers.
In this paper Mendel announces his experiments on pea plant breeding:
• Mendel G. (1895) Experiments in Plant Hybridization.
You can find this on YouTube by searching for "Eric Lander MIT Genetics Youtube."  This is the best description of Mendel's work that I know of:
• Lect. 6, MIT 7.012 Introduction to Biology, Fall 2004.
  This paper reveals the first chromosome map resulting from the analysis of recombination frequencies by Sturtevant:
• Sturtevant, A.H. (1913) The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association.  Journal of Experimental Zoology, 14: 43-59.
This article is a fun look at what life would be like if Boltzmann's constant had a much larger value, and also provides an informative introduction to some of the statistical physics concepts we'll be exploring in the course:
• Prentis, J.J. (1996) Thank you, Boltzmann, that your constant is so small.  The Physics Teacher, 34: 392-397.
This article is the source of several figures from today's lecture on chromosome geographies in eukaryotes:
• Cremer, T. and Cremer, C. (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat. Rev. Genet. 2(4): 292-301.
  
  
• Lecture 7 (pptx/ppt/pdf)
  
  Additional reading and useful links for Lecture 7:
This paper is the basis of our discussion of the chromosome geography in Vibrio:
• Fiebig A., Keren K., and Theriot J. (2006) Fine-scale time-lapse analysis of the biphasic, dynamic behaviour of the two Vibrio cholerae chromosomes.  Molec. Microbiol. 60(5): 1164-1178.
  This site has some of the history of GFP:
• http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP-1.htm
The wikipedia article on Philadelphia chromosome that Rob mentioned in class:
• http://en.wikipedia.org/wiki/Philadelphia_chromosome
  
The article Rob referenced in class demonstrating the technique of using fluorescent proteins to look at chromosome geography in live cells:
• Gitai Z., Thanbichler M., and Shapiro L. (2005) The choreographed dynamics of bacterial chromosomes. Trends in Microbiology 13(5): 221-228.
  
  
• Lecture 8 (pptx/ppt/pdf)
  
  Additional reading and useful links for Lecture 8:
Some resources on statistical mechanics:
• Garcia, H.G., Kondev J., Orme N., Theriot J.A., and Phillips R. (2007) A first exposure to statistical mechanics for life scientists: Applications to binding.
• Notes on statistical mechanics
This paper discusses what growth rates can tell us about how cells work (Rob mentioned it in class in the context of gene regulation):
• Neidhardt F. C. (1999) Bacterial Growth: Constant Obsession with dN/dt.  J. Bacteriol. 181(24): 7405-7408.
This paper is the paper mentioned in class that discusses the entropic configurations of linear versus circular chromosomes:
• Jun, S. and Mulder, B. (2006) Entropy-driven spatial organization of highly confined polymers: Lessons for the bacterial chromosome. PNAS 103(33): 12388-12393.
  


• Lecture 9 (see Lecture 8 slides)
  
  Additional reading and useful links for Lecture 9:
            Rob mentioned this group's experiments on observing transcription and translation simultaneously:
• Singer lab website


• Lecture 10 (pptx/ppt/pdf)--special lecture on evolution in honor of Darwin's birthday
  
  Additional reading and useful links for Lecture 10:
This news article describes the work from the Lenski group on their 30 year evolution experiment:
• http://www.sciencenews.org/view/feature/id/40006/title/Molecular_Evolution
This site has a collection of information on Wallace's life and work; look at the two papers labeled S20 and S43, these are two of Wallace's great papers that report on his thinking as he traveled through the Malay archipelago:
• http://www.wku.edu/~smithch/index1.htm
This site describes the work of the Relman lab on the different microbial communities in our mouths:
• http://asiago.stanford.edu/RelmanLab/research_browser.php?link=6
  Some papers mentioned in class:
• Abzhanov A., Protas M., Grant B.R., Grant P.R., Tabin C.J. (2004) Bmp4 and morphological variation of beaks in Darwin's finches. Science 305(5689): 1462-5.
• Dunning Hotopp, J.C., et al. (2007) Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Science 317 (1753): 1753-6. 
• Yunis J.J. and Prakash O. (1982) The origin of man: a chromosomal pictorial legacy. Science 215(4539): 1525-30.
• Hillier et al. (2005) Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature 434(7034): 724-31.
• Zuckerkandl E., Jones R.T., and Pauling L. (1960) A comparison of animal hemoglobins by tryptic peptide pattern analysis. PNAS 2046: 1349-1360.
Books mentioned in class:

• Sean Carroll, Into the Jungle.
• Neil Shubin, Your Inner Fish.
  
  
• Lecture 11 (pptx/ppt/pdf)
  
  Additional reading and useful links for Lecture 11:
This is the experimental paper that showed the synthetic genetic switch:
• Gardner T.S., Cantor C.R., and Collins J.J. (2000) Construction of a genetic toggle switch in Escherichia coli.  Nature 403: 339.
This paper showed how a synthetic transcriptional oscillator could be constructed in bacteria:
• Elowitz M.B., and Leibler S. (2000) A synthetic oscillatory network of transcriptional regulators.  Nature 403: 335.
This paper gives a very nice theoretical discussion of genetic switches:
• Cherry J.L. and Adler F.R. (2000) How to make a biological switch.  J. Theor. Biol. 203: 117.
This interesting paper will be relevant to the homework since it shows the puzzle of how flies maintain their overall body plans with correct scaling for widely different embryo sizes:
• Gregor T., Bialek W., de Ruyter van Stevenick R.R., Tank D.W., and Wieschaus E. (2005) Diffusion and scaling during early embryonic pattern formation.  PNAS 102 (51) 18403-18407.
This paper shows single-cell trancsription measurements on E. coli and will serve as the basis for a homework problem:
• Golding I., Paulsson J., Zawilski S.M., and Cox E.C. (2005) Real-time kinetics of gene activity in individual bacteria.  Cell 123 (16): 1025-36.
This interesting paper explores a general method for computing the moments of the mRNA distribution function like that we discussed in class, but more general:
• Sanchez A. and Kondev J. (2008) Transcriptional control of noise in gene expression. PNAS 105 (13) 5081-5086.
  Rob mentioned this book in class as one of the five best books in all of science or something along those lines:
• Mark Ptashne, A Genetic Switch.


3. Signalling
   
   
• Lecture 12
  
  
4. Mechanosensation
   
   
• Lecture 13
  
  
5. Evolution - see Lecture 10


• Suggested Reading:
  
  • Losos et al. (2004) Predator-induced behaviour shifts and natural selection in field-experimental lizard populations. Nature, 432:505-8
  • 15 Evolution Gems from Nature.com
  This set of papers show the vibrant state of the study of evolution 150 years after the publication of Wallace and Darwin's discoveries about the variability of species and natural selection.

 

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