Papers to Read


The papers provided here are meant to provide an entry point into the literature for going more deeply into various topics covered 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 of 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.

- Sean Eddy, (2004), What is Bayesian statistics?, Nature Biotechnology, 22, 1177-178.This paper gives a compact but beautiful example of the power of Bayesian methods for figuring out the probability of some hypothesis given the data.

- 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:

- Hernan Garcia and Rob Phillips, (20011), Quantitative dissection of the simple repression input-output function, PNAS, 108, 29, 12173-8.This paper demonstrates that thermodynamic models can make quantitative predictions about the level of gene expression as a a function of repressor copy number and operator strength.

- 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.

Biophysics of Vision:

Reading suggestions will be posted during the course.

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.

- Eran Segal etal., (2006), A genomic code for nucleosome positioning, Nature, 442, 772-778. This paper describe work aimed at determining genome wide nucleosome positioning preferences.

- 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.

- Paul Wiggins etal., (2010), Strong intranucleoid interactions organize the E. coli chromosome into a nucleoid filament, PNAS, 107, 4991-5. This paper looks at the spatial organization of the genome in a cell.

- 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.

- Alexander Tsankov etal., (2010), The role of nucleosome positioning in the evolution of gene regulation, PLoS Biology, 8, e1000414. This interesting paper examines the genome-wide nucleosome positions in 12 different yeast species. This data provides an excellent jumping off point for models of nucleosome positioning.

- 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.


- 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



Van Oijen 2006 - This paper presents a beautiful single-molecule study of how DNA replication works.

Gotta, Miller, French 1991 rRNA Transcription Rate in Escherichia coli - This classic experiment used the drug rifampin to inhibit transcription inititation and electron microscopy to measure the rate of transcription.

Baker, Bell 1998 Polymerases and the replisome machines within machines - This paper describes the molecular machines responsible for DNA replication and provides a very graphic everyday interpretation of the amazing fidelity of this process.

Barnett 2003 Beginnings of microbiology and biochemistry - This paper gives an overview of the tremendous importance of yeast to the study of both biochemistry and biology.

Wigner Unreasonable effectiveness of mathematics


Neidhardt Bacterial Growth 1999


Roellig 2011 SnapShot the segmentation clock - This paper has a beautiful description of the clock and wavefront model with interesting movie.

Schroter Oates 2010 Segmentation clock period mutant - This beautiful paper describes systematic experiments designed to test the clock-wavefront in developing zebrafish.

Gomez et al 2008 Control of segment number in vertebrate - This interesting paper explores how the clock-wavefront model can be used
to interpret differences in number of vertebrae between different species.

Cooke Zeeman 1976 Wavefront model for morphogenesis - This paper introduced the so-called clock and wavefront mechanism that attempts to
explain features such as somitogensis.


Mahajan Street Fighting Mathematics