Lecture Slides
Lecture slides will periodically added here throughout the course. These links will be password protected, so please do not share these slides outside of the course.
Papers Mentioned During Class
Monday, January 11
These two papers represent the state of the art in measuring the number of proteins in E. coli.
Paper on a powerful new imaging tool, the lattice light-sheet microscope. This was developed by the lab of Eric Betzig.
Related to Rob's comments on turning our thinking about biology into formal mathematical predictions and confronting that math with experiments that haven't been performed before to demonstrate our understanding.
Great resource on educated guessing and problem solving. Free download!
Tuesday, January 12
Check out Li et al. and Schimdt et al. above! Li et al. count the protein copy number in E. coli with seqeuncing (Protect-Seq). Schimdt et al. count the copy number with mass spectrometry.
This paper applies recent advances in superresolution imagining to quantiate the spatial distributions of ribosomes and RNA polymerase in E. coli.
Single-molecule measurement of DNA replication. We used this data in class to estimate the DNA replication rate.
Here the authors use electron microscopy to measure the transcription rate in E. coli .
Wednesday, January 13
Quantitative imaging of transcription in Drosophila embryos. Garcia et al. uses the clever MS2 technique that Rob spoke about.
Thursday, January 14
An early paper that characterizes chemotaxis by E. coli under different conditions.
Using two optical tweezers traps (like you have been building in lab), they trap E. coli and study its swimming and tumbling.
This is the paper that uses the FRET technique.
Monday, January 18
Two papers on counting production of mRNA that Rob spoke about.
Two cool papers that demonstrate we can quantitatively predict protein expression from the simple repression regulatory construct. Each uses a different way to count the lac repressor copy number in E. coli
Tuesday, January 19
How can cells manage to perform replication, transcription, and translation with such low error rates!? This paper from John Hopfield is on kinetic proofreading and is very relavent to the lecture today.
Wednesday, January 20
Prediction of gut structure using ideas from mechanics.
Early work studying the concentration gradient of bicoid protein in the Drosophila embryo.
This paper considers the Clock and Wavefront model for somitogenesis in Zebrafish. They make use of a mutant Zebrafish (in the hes6 gene) to test out some prediction from the model.
Thursday, January 21
Further reading
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:
List of key numbers in biology, such as the quantity and size of cellular components and the rates of cellular processes.
This paper describes the role of biological numeracy in thinking about a variety of problems.
This paper gives a compact but beautiful example of the power of Bayesian methods for figuring out the probability ofsome hypothesis given the data.
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
This paper demonstrates that thermodynamic models can make quantitative predictions about the level of gene expression as a function of repressor copy number and operator strength.
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.
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.
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.
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
This paper shows how a simple model of excluded volume predicts how nucleosomes will be organized around promoters.
This paper describe work aimed at determining genome wide nucleosome positioning preferences.
This paper describe work aimed at determining genome wide nucleosome positioning preferences.
This paper looks at the spatial organization of the genome in a cell.
In this paper, optical tweezers are used to study the forces needed to package double-stranded DNA into a viral capsid.
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.
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:
Quantitative analysis reveals that diffusion based mechanism cannot account for morphogen gradient scaling in early embryos across closely related fly species.
Evolution
This classic article makes a compelling case for the primacy of evolution in the study of biology.