Recommended readings

These papers are to provide you an entry into the original literature on the subjects covered in class, primarily in case you want to dig more deeply into any of the topics we cover in class. These papers have been picked either because they provide interesting and provocative experimental measurements of particular biological phenomena or because they show how to go about constructing theoretical models in the physical biology spirit described in the course.

The papers that are of the most direct relevance to what we will cover in class are linked on the "Syllabus" part of the website.

Biology by the numbers:

- Uri Moran etal., (2010), SnapShot: Key Numbers in Biology, Cell, 141, 1262. List of key numbers in biology, such as the quantity and size of cellular components and the rates of cellular processes.

- Rob Phillips and Ron Milo, (2009), A Feeling for the numbers in Biology,PNAS, 106, 21465-71. This paper describes the role of biological numeracy in thinking about a variety of problems.

- Hernan Garcia, etal., (2007), A First Exposure to Statistical Mechanics for Life Scientists This paper is a brief introduction to ideas from statistical mechanics that can be used to analyze a variety of problems in biology.

Regulatory biology:

- Lacromioara Bintu, etal., (2005), Transcriptional regulation by the numbers: models, Current Opinions in Genetics and Development, 15, 116-124. This paper outlines an approach to creating quantitative models of gene expression using thermodynamics of the binding of transcription factors and RNA polymerase to DNA.

- Lacramioara Bintu etal., (2005), Transcriptional regulation by the numbers: applications, Current Opinions in Genetics and Development, 15, 125-35. This paper outlines an approach of applying thermodynamic models to gene regulation.

- Ido Golding, (2005), Real-time kinetics of gene activity in individual bacteria, Cell, 123, 1025-036.This paper clearly demonstrates that the process by which mRNA is produced in the E.coli cell is stochastic in nature. A surprising observation is that the mRNA distribution is not Poisson, characterized by bursts in mRNA production. To this day the source of the stochasticity remains a mystery.

- Victor Sourjik and Howard C. Berg, (2002), Receptor sensitivity in bacterial chemotaxis, PNAS, 99, 123-127. and Victor Sourjik and Howard C. Berg, (2002), Binding of the Escherichia coli response regulator CheY to its target measured in vivo by fluorescence resonance energy transfer, PNAS, 99, 12669-12674. These two papers use the method of FRET to examine the relation between chemoattractant concentration and the chemical reactions within cells that control the frequency of tumbles.

- Juan Keymer etal.,(2006), Chemosensing in Escherichia coli: Two regimes of two-state receptors, PNAS, 103, 1786-1791. and Bernardo A. Mello and Yuhai Tu, (2005), An allosteric model for heterogeneous receptor complexes: Understanding bacterial chemotaxis responses to multiple stimuli, PNAS, 99, 12669-12674. Theory of chemotaxis: These two papers show how simple ideas from equilibrium statistical mechanics can be used to understand the chemotactic response of E. coli to different concentrations of chemoattractant.

- Taejin Min etal., (2009), High-resolution, long-term characterization of bacterial motility using optical tweezers, Nature Methods, 6, 831-35. Through a combination of light microscopy and optical trapping, the swimming of single Escherichia coli cells is recorded over long time periods to find the statistics of flagellar activity.

Membranes by the numbers:

- Tomas Kirchhausen, (2000), Nature Reviews Molecular Cell Biology, 1, 187-198.This paper gives a description of different ways that cells make vesicles and gives some quantitative insights into the rate of vesicle formation.

- Tristan Ursell, etal., (2007), The Role of Lipid Bilayer Mechanics in Mechanosensation, in A. Kamkin and I. Kiseleva (eds.), ”Mechanosensitive Ion Channels,” Springer. Review article focused on continuum and statistical mechanics models of the response of mechanosensitive ion channels to membrane tension. In particular, they summarize models of protein shape, thickness mismatch, and interactions among crowded proteins on channel function. We will work out some of these models together.

- Aurelien Roux, etal., (2010), Membrane curvature controls dynamin polymerization, PNAS, 107, 4141-146.This is a fun research article by Roux et al. which appeared last year in PNAS. It concerns the binding of dynamin to regions of high membrane curvature. We’ll use it as a case study of how proteins dynamically re-model membrane in way that is essential to membrane trafficking.

The Physics of Genome Management:

- Roger Kornberg and Lubert Stryer, (1988), Statistical distibutions of nucleosome: nonrandom locations by a stochastic mechanism, Nucleic Acids Research, 16, 6677-6690.This paper shows how a simple model of excluded volume predicts how nucleosomes will be organized around promoters.

- Noam Kaplan etal., (2009), The DNA-encoded nucleosome organization of a euakryotic genome, Nature, 458, 362-366. This paper describe work aimed at determining genome wide nucleosome positioning preferences.

- Douglas Smith etal., (2001), The bacteriophage phi29 portal motor can package DNA against a large interanl force, Nature, 413, 748-752. In this paper, optical tweezers are used to study the forces needed to package double-stranded DNA into a viral capsid.

- K.J. Polach and J. Widom, (1995), Mechanism of protein access to specific DNA sequences in chromatin: A dynamic equilibrium model for gene regulation, JMB, 254, 130-149. This paper examines how different sites within nucleosomes grant access to DNA binding proteins and quantifies how this accessibility depends upon the depth of the sites of interest within the nucleosome.

Pattern formation in biology:

- Thomas Gregor, etal., (2005), Diffusion and scaling during early embryonic pattern formation, PNAS, 102, 18403-407.Quantitative analysis reveals that diffusion based mechanism cannot account for morphogen gradient scaling in early embryos across closely related fly species.

- A.M. Turing, (1952), The Chemical Basis of Morphogenesis, Philosophical Transactions of the Royal Society of London. Series B. Biological Sciences, 237, 37-72. Turing demonstrates how reaction-diffusion systems can lead to pattern formation, and suggests that patterns in biology may be established through similar mechanisms.


- Alfred Wallace, (1858), On the tendency of varieties to depart indefinitely from the original type. This paper announces Wallace's independent discovery of the mechanism of evolution, namely, natural selection.

- Alfred Wallace, (1855), On the law which has regulated the introduction of new species. In this paper, Wallace describes his discovery of the fact of evolution and writes about the relatedness of species in space (geography) and time (geological record).

Dobzhansky 1973, "Nothing in Biology Makes Sense Except in the Light of Evolution". This classic article makes a compelling case for the primacy of evolution in the study of biology.


Papers brought up during the class



Unreasonable effectiveness of mathematics Wigner

S.R. Quake, "Precision Measurement in Biology", in Physical Biology: From Atoms to Medicine, ed. Ahmed Zewail. Imperial College Pres (2008), (see page 411-426 for Quake article)

Polymerases and the Replisome: Machines within Machines, Baker Cell 1998

Wednesday: Look here for Stephen's Smalls talk on AP Patterning in Drosophila: Experimental Tests of the Morphogen Hypothesis The poster of proteins Rob showed during class. A glossary of genetics for your phone.


Prentiss Boltzmann Constant

Gorter and Grendel

guantes two-component oscillators, guantes supporting information This paper describes a minimal approach to constructing oscillators based upon a network in which an activator and repressor interact.