APh 161 - Physical Biology of the Cell
Image from Dennis Kunkel. The image shows various cell types in blood.
- Today's lecture (March 6) will be the last of the term
- Molecule Viewers
- Online Resources
- Articles
- Understanding the Immune System: How It Works
"This tutorial explains the molecules, cells and tissues of the immune system. Since the course this year will draw many examples from the study of viruses and the immune system, this article is a useful place to learn some of the background."
- McGregor; "How to get ahead: the origin, evolution and function of bicoid", Bioessays. Sep 2005; 27(9):904-13.
"One of the themes we will examine in the course is the connection between development and evolution. This article gives part of the interesting story of one of the key proteins in dictating the anterior-posterior patterning in the fruit fly embryo."
- Palumbi; "Humans as the World's Greatest Evolutionary Force", Science. 7 Sep 2001; 293(5536):1786-90.
"This interesting paper examines the economic and social
consequences of evolution. I give it to you as an amusing read."
- Bray; "Reasoning for results", Nature. 30 Aug 2001; 412(6850):863.
"This article makes a case for the role of theory in biology."
- Wingreen and Botstein; "Back to the future: education for systems-level biologists", Nat Rev Mol Cell Biol. Nov 2006; 7(11):829-32.
"This article describes a course similar to ours at Princeton, though in their case, the course is based upon reading of certain classic or important papers."
- Molecular Motors and Transport
- Blasius et al.; "Two binding partners cooperate to activate the molecular motor kinesin-1"
- Cai et al.; "Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells"
- PBoC Table of Contents
- HW 1 (problems, solutions)
due 1/16/07
Reading
Links
- PDB coordinates (zip, tgz)
"This archive has the PDB coordinates you need for Problem 3."
- White blood cell
(click on image for a larger version)
"You may assume that the diameter of the cell is 10 microns. However, note the annoying feature of many of the microscopy figures that appear in books and on the web of not having scale bars."
Related articles
- Whitman et al; "Prokaryotes: the unseen majority", Proc Nat Acad Sci. Jun 1998; 95(12):6578.
- Zimmerman and Trach; "Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli", J Mol Biol. Dec 1991; 222(3):599.
- HW 2 (problems, solutions)
due 1/23/07
Reading
Links
Related articles
- Briggs et al.; "The stoichiometry of Gag protein in HIV-1", Nat Struct Mol Biol. Jul 2004; 11(7):672-5.
"This paper shows electron microscopy images of immature HIV virus particles that you will need in problem 1."
- Briggs et al.; "The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions", Structure. Jan 2006; 14(1):15-20.
"This paper is a second paper by Briggs et al. that shows mature virus particles and will permit you to measure the dimensions of the HIV capsid."
- HW 3 (problems, solutions)
due 1/30/07
Reading
Links
Related articles
- Problem 1
PBoC chapter 7 "Two-State Systems: From Ion Channels to the Polymerase Chain Reaction"
Imai; "Precision determination and Adair scheme analysis of oxygen equilibrium curves of concentrated hemoglobin solution. A strict examination of Adair constant evaluation methods", Biophys Chem. 31 Aug 1990; 37(1-3):197-210.
Imai; "Adair fitting to oxygen equilibrium curves of hemoglobin", Methods Enzymol. 1994; 232:559-76.
Klotz; "Hemoglobin-oxygen equilibria: retrospective and phenomenological perspective", Biophys Chem. 2003; 100(1-3):123-9.
"The first few pages of this article provide a useful and brief overview of thinking on hemoglobin. Note that in Table 1 the units should be mmHg^-1. I don't know what to say about the stuff near the end of the article."
- Problem 2(c)
Oehler, Amouyal, Kolkhof, von Wilcken-Bergmann, Müller-Hill; "Quality and position of the three lac operators of E. coli define efficiency of repression", EMBO J. Jul 1994; 13(14):3348.
- HW 4 (problems, solutions)
due 2/20/07
Reading
Links
Related articles
- Polach and Widom; "Mechanism of protein access to specific DNA sequences in chromatin: a dynamic equilibrium model for gene regulation", J Mol Biol. 24 Nov 1995; 254(2):130-49.
"This experiment addresses the equilibrium accessibility of protein binding sites that are buried inside nucleosomal DNA."
- Lowary and Widom; "New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning", J Mol Biol. 13 Feb 1998; 276(1):19-42.
"The authors evolve DNA sequences selecting for those that bind the best to nucleosomes. The result is a set of rules that can be used to predict if a nucleosome will bind preferentially to a certain DNA molecule by looking at its sequence."
- HW 5 (problems, solutions)
due 3/1/07
Reading
Links
Related articles
- Statistical Mechanics
- Lecture #1: "Anatomy of Blood Test" (ppt, pdf) 1/4/07
Links
- Complete Blood Count (CBC)
"This website gives a nice description of the complete blood count (CBC) and comments on the numbers that emerge from such a test."
- Introduction to ELISA Activity
"This website gives a brief, but informative description of the Elisa test described in class."
- Lecture #2: "Cells and What They Are Made Of" (ppt, pdf) 1/9/07
Links
Related articles
- Barnett; "Beginnings of microbiology and biochemistry: the contribution of yeast research", Microbiology. Mar 2003; 149(pt 3):557.
- Ecker and Schaechter; "Ribosome content and the rate of growth of salmonella typhimurium", Biochim Biophys Acta. 15 Oct 1963; 76:275-9.
- Pedersen, Bloch, Reeh and Neidhardt; "Patterns of Protein Synthesis in E. coli: a Catalog of the Amount of 140 Individual Proteins at Different Growth Rates", Cell. May 1978; 14(1):179.
"This paper attempts to take a molecular census of an E. coli cell and was the quantitative inspiration for the famous cartoons of Goodsell."
- Lecture #3: "Viruses: Structure and Molecular Census" (ppt, pdf) 1/11/07
Links
- Virus Images
"This website gives a sense of the beautiful assembly process of the tobacco mosaic virus."
- Molecules of HIV
"This website will help you understand the parts list of the HIV virus."
Related articles
- Benjamin et al.; "Three-dimensional structure of HIV-1 virus-like particles by electron cryotomography", J Mol Biol. 18 Feb 2005; 346(2):577-88.
"This paper uses cryo-electron microscopy to provide insights into the structure of HIV."
- Brügger et al.; "The HIV lipidome: a raft with an unusual composition", Proc Natl Acad Sci USA. 21 Feb 2006; 103(8):2641-6.
"This interesting paper reports on measurements of the lipid content of HIV virions. It is worth your while to see what methods are used to carry out these quantitative assays."
- Suttle; "Viruses in the sea", Nature. 15 Sep 2005; 437(7057):356-61.
"This paper describes recent attempts to take stock of bacteriophage diversity in the oceans."
- Briggs et al.; "The mechanism of HIV-1 core assembly: insights from three-dimensional reconstructions of authentic virions", Structure. Jan 2006; 14(1):15-20.
"This paper provides a cryo electron microscopy study of HIV. We will use the numbers from this paper to make estimates about the size of HIV and its molecular inventory."
- Baker et al.; "Adding the third dimension to virus life cycles: three-dimensional reconstruction of icosahedral viruses from cryo-electron micrographs", Microbiol Mol Biol Rev. Dec 1999; 63(4):862-922.
"This gorgeous paper gives a variety of structural insights into the construction of viruses."
- Turner and Summers; "Structural biology of HIV", J Mol Biol. 8 Jan 1999; 285(1):1-32.
"This article gives a tour of the different proteins that make up the HIV virus."
- Lecture #4: "The Biological Uses of Binding" (ppt, pdf) 1/16/07
Links
Related articles
- Ladbury; "Application of isothermal titration calorimetry in the biological sciences: things are heating up!", Biotechniques. Dec 2004; 37(6):885-7
- Velazquez-Campoy et al.; "The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design", Arch Biochem Biophys. 15 Jun 2001; 390(2):169-75.
- Lecture #5 (no slides) 1/18/07
Related articles
- Keymer et al.; "Bacterial metapopulations in nanofabricated landscapes", Proc Natl Acad Sci USA. 14 Nov 2006; 103(46):17290-5.
- Neidhardt; "Bacterial Growth: Constant Obsession with dN/dt", J Bacteriol. Dec 1999; 181(24):7405.
"This personal account describes the views of a microbiologist about the interest of studying dN/dt in cell cultures."
- Monod; "The Growth of Bacterial Cultures", Annual Review of Microbiology. 1949; 3(1):371.
"This paper by Monod describes quantitative studies of bacterial growth. The final figure illustrates the kind of growth curves that led to the elucidation of the operon concept.
- Lecture #6: "Feedback and Dynamics in Cells" (pdf) 1/23/07
Links
Related articles
- Lecture #7: "Biological Circuit (Design)" (pdf) 1/25/07
Links
Related articles
- Lecture #8: "DNA Packing in Viruses" (ppt, pdf) 1/30/07
Related articles
- Richmond and Davey; "The structure of DNA in the nucleosome core", Nature. May 2003; 423(6936):145-50.
- Polach and Widom; "A model for the cooperative binding of eukaryotic regulatory proteins to nucleosomal target sites", J Mol Biol. 24 May 1996; 258(5):800-12.
- Polach and Widom; "Mechanism of protein access to specific DNA sequences in chromatin: a dynamic equilibrium model for gene regulation", J Mol Biol. 24 Nov 1995; 254(2):130-49.
"These two papers describe experiments on the equilibrium accessibility of nucleosomes"
- Segal et al.; "A genomic code for nucleosome positioning", Nature. 17 Aug 2006; 442(7104):772-8.
"This paper argues that nucleosomes care where they are located on genomic DNA. This implies a secondary "code" for nucleosome positioning that may have many functional implications."
- Lecture #9: "DNA packing in eukaryotes and nucleosomal DNA accessibility" (ppt, pdf) 2/13/07, 2/15/07
Related articles
- Lowary and Widom; "New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning", J Mol Biol. 13 Feb 1998; 276(1):19-42.
"The authors evolve DNA sequences selecting for those that bind the best to nucleosomes. The result is a set of rules that can be used to predict if a nucleosome will bind preferentially to a certain DNA molecule by looking at its sequence."
- Polach and Widom; "Mechanism of protein access to specific DNA sequences in chromatin: a dynamic equilibrium model for gene regulation", J Mol Biol. 24 Nov 1995; 254(2):130-49.
"This experiment addresses the equilibrium accessibility of protein binding sites that are buried inside nucleosomal DNA."
- Luger et al.; "Crystal structure of the nucleosome core particle at 2.8 Å resolution", Nature. 18 Sep 1997; 389(6648):251-60.
- Davey et al.; "Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution", J Mol Biol. 21 Jun 2002; 319(5):1097-113.
- Richmond and Davey; "The structure of DNA in the nucleosome core", Nature. 8 May 2003; 423(6936):145-50.
"These are crystal structures of the nucleosome core particle. They reveal all sorts of interesting details about the DNA conformation and the nature of the DNA-histone interaction."
- Rippe; "Making contacts on a nucleic acid polymer", Trends Biochem Sci. Dec 2001; 26(12):733-40.
"Very useful review and great introduction to thinking of DNA as a polymer, both in vivo and in vitro."
- Lecture #10: "Chromosome Geography" (ppt, pdf) 2/20/07
Related articles
- Cremer and Cremer; "Chromosome territories, nuclear architecture and gene regulation in mammalian cells", Nat Rev Genet. Apr 2001; 2(4):292-301.
"This article is a comprehensive review of the experimental background behind the claim that chromosomes are organized into territories."
- Fiebig et al.; "Fine-scale time-lapse analysis of the biphasic, dynamic behaviour of the two Vibrio cholerae chromosomes", Mol Microbiol. Jun 2006; 60(5):1164-78.
"This article shows how the two chromosomes in Vibrio are ordered in space and will serve as the basis for the analysis carried out in class."
- Hahnfeldt et al.; "Polymer models for interphase chromosomes", Proc Natl Acad Sci USA. 15 Aug 1993; 90(16):7854-8.
"This paper shows the kind of theoretical reasoning that can be brought to bear on the problem of chromosome geography."
- Bystricky et al.; "Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques", Proc Natl Acad Sci USA. 23 Nov 2004; 101(47):16495-500.
"This paper is a modern experiment that shows how fluorescently labeled DNA-binding proteins can be used to map out the geography of chromosomes. In addition to showing physical distance vs genomic distance, this work also reports the distributions."
- Gitai et al.; "The choreographed dynamics of bacterial chromosomes", Trends Microbiol. May 2005; 13(5):221-8.
"This paper shows describes the important progress in understanding the ordered arrangements of bacterial chromosomes."
- Yokota et al.; "Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus", J Cell Biol. 27 Dec 1999; 147(7):1583.
"This paper reports on some of the pioneering experimental work that resulted in the picture of chromosome territories."
- Lecture #11: "Chemotaxis" (ppt, pdf) 2/27/07
Related articles
- Graham and Duke; "The logical repertoire of ligand-binding proteins", Phys Biol. 24 Aug 2005; 2(3):159-65.
- Kentner and Sourjik; "Spatial organization of the bacterial chemotaxis system", Curr Opin Microbiol. Dec 2006; 9(6):619-24.
- Barkai and Leibler; "Robustness in simple biochemical networks", Nature. 26 Jun 1997; 387(6636):913-7.
- Bialek and Setayeshgar; "Physical limits to biochemical signaling", Proc Natl Acad Sci USA. 19 Jul 2005; 102(29):10040-5.
- Purcell; "Life at low Reynolds number", Am J Phys. Jan 1977; 45(1):3-11.
- "Motile Behavior of Bacteria" by Howard Berg
"This article gives a wonderful introduction to the study of chemotaxis in bacteria."
- Computer Models of Bacterial Chemotaxis (Bray Group @ Cambridge)
"This webpage has many interesting insights into bacterial chemotaxis including many important physical and chemical parameters associated with the process."
- Keymer et al.; "Chemosensing in Escherichia coli: two regimes of two-state receptors", Proc Natl Acad Sci USA. 7 Feb 2006; 103(6):1786-91.
"This paper describes a simple, but powerful modeling framework for thinking about the sensitivity and dynamic range of the chemotaxis system in E. coli."
- Sourjik and Berg; "Receptor sensitivity in bacterial chemotaxis", Proc Natl Acad Sci USA. 8 Jan 2002; 99(1):123-7.
"This paper reports on beautiful in vivo FRET measurements which make it possible to analyze the response of the E. coli chemotaxis apparatus to differing amounts of chemoattractant."
- Lecture #12: "Membranes" (ppt, pdf) 3/1/07
Related articles
- Helfrich; "Elastic properties of lipid bilayers: theory and possible experiments", Z Naturforsch [C]. Nov-Dec 1973; 28(11):693-703.
"This classic is Helfrich's original article on the calculation of the energy associated with bending lipid bilayers."
- Kamien; "The geometry of soft materials: a primer", Rev Mod Phys. Oct 2002; 74(4):953-71.
"Kamien has a nice review here of differential geometry giving examples from soft materials (like lipid bilayers)."
- Kirchhausen; "Three ways to make a vesicle", Nat Rev Mol Cell Biol. Dec 2000; 1(3):187-98.
"This review by Kirchhausen inspired our estimate of vesicle formation in fibroblasts and has a stimulating discussion of the ways that cells use proteins to make vesicles."
- Lecture #13: "Mechanics of Membrane Structures" (ppt, pdf) 3/6/07
Related articles
- Sprong et al.; "How proteins move lipids and lipids move proteins", Nat Rev Mol Cell Biol. Jul 2001; 2(7):504-13.
- Voeltz et al.; "Structural organization of the endoplasmic reticulum", EMBO Rep. Oct 2002; 3(10):944-50.
- Hirokawa; "Kinesin and dynein superfamily proteins and the mechanism of organelle transport", Science. 23 Jan 1998; 279(5350):519-26.
- Voeltz and Prinz; "Sheets, ribbons and tubules - how organelles get their shape", Nat Rev Mol Cell Biol. Mar 2007; 8(3):258-64.
"A nice exposition on some of the mechanisms that have been implicated in determining the shape of membrane-bound organelles like the Golgi, mitochondria and the ER."
- Koster et al.; "Membrane tube formation from giant vesicles by dynamic association of motor proteins", Proc Natl Acad Sci USA. 23 Dec 2003; 100(26):15583-8.
"This paper shows how motor proteins can form membrane tubes."
- Virus Assembly
- Hicks and Henley; "Irreversible growth model for virus capsid assembly", Phys Rev E. Sep 2006; 74(3 Pt 1):031912.
- Zandi et al.; "Classical Nucleation Theory of Virus Capsids", Biophys J. 15 Mar 2006; 90(6):1939-48.
- Rob Phillips
159 Broad
x3374
phillips AT pboc.caltech.edu
- David Van Valen
155 Broad
x5876
vanvalen AT caltech.edu
- Eric Peterson
155 Broad
x5876
eric AT caltech.edu
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