Rob's problem set 1
Sanjoy's problem set

Notes and Slides

Jané Kondev
Lecture Notes
Lecture Slides

Patricia Bassereau
Lecture Slides

Rob Phillips
Estimating the size of lipids

Aleksandra Walczak
Board notes on information theory.

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, (2011), 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.

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.


- 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 and websites brought up during the class



- The End of Theory: The Data Deluge Makes the Scientific Method Obsolete
- Daniel Simberloff and Edward Olson (1968), Experimental Zoogeography of Islands: The Colonization of Empty Islands


- Garcia et al. (2008), A First Exposure to Statistical Mechanics for Life Scientists.
- Sidney L. Shaw and Edward H. Hinchcliffe (2013), 65000 Shades of Grey: Use of Digital Image Files in Light Microscopy
- Online color challenge


- Kim, MunJu et al. (2013), A macroscopic scale model of bacterial flagellar bundling and Supplemental Movie 1.
- Rob Phillips (2013), In Retrospect: The Feynman Lectures on Physics
- Rossi-Fanelli, A. and E. Antonini (1958), Studies on the Oxygen and Carbon Monoxide Equilibria of Human Myoglobin.
- Hoekstra, Hopi E. et al (2006), A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern
- Luria, S. E. and M. Delbrück (1943), Mutations of Bacteria from Virus Sensitivity to Virus Resistance.
- Chuang, John S. et al. (2009), Simpson's Paradox in a Synthetic Microbial System.
- Chuang, John S. et al. (2010), Cooperation and Hamilton's rule in a simple synthetic microbial system and the supplemental information.
- Ndifon, Wilfred et al. (2012), Chromatin conformation governs T-cell receptor Jβ gene segment usage.

- Propagation of error.