MCB137 - Physical Biology of the Cell

Biology is being revolutionized by new experimental techniques that have made it possible to measure the inner workings of molecules, cells and multicellular organisms with unprecedented precision. The objective of this short module is to explore this deluge of quantitative data through the use of biological numeracy. We will survey exciting research examples from our department and beyond in order to develop theoretical models that make precise predictions about biological phenomena. These predictions will be tested through the hands-on analysis of experimental data and by performing numerical simulations using Matlab.

Physical biology will be introduced as an exciting new tool to complement other approaches within biology such as genetics, genomics and structural biology. The module will introduce students to the enabling power of biological numeracy in scientific discovery and make it possible for them to use these tools in their own research.

Course instructor: Hernan Garcia (hggarcia@berkeley.edu). Office hours: Thursdays 4pm to 5pm at 501C LSA.

Course TA: Simon Alamos (simon.alamos@berkeley.edu). Office hours: Mondays 4pm to 5pm outside of 501C LSA.

Class materials:

Schedule: Class meets Tuesdays and Thursdays in 150D Moffitt from 2pm to 4pm (lecture and lab/discussion).

Homework policy: Homeworks are due at the beginning of class one week after they are posted.  Solutions will be posted two days after the homeworks are submitted, and homeworks will be returned a week after they are submitted. NO late homeworks will be accepted (late means anytime after class starts the day the homework is due) unless you have a note from someone like a doctor or a Dean. You may discuss the homework with others, but your explanations and derivations must be your own. Your logic and the significance of your results should also be explained.

 

 

Class date

Topics

Materials

1/17

A feeling for the numbers in biology: Estimation and biological numeracy

E. coli by the Numbers

A feeling for the numbers: PowerPoint Presentation

Matlab tutorials: 1 and 2

1/19

E. coli by the Numbers

Making simple plots: Matlab code

Adding scale bars to images: Images, Matlab code 

1/24

Bacterial growth: Physical limits to bacterial growth

 

Homework 1 out, due 1/31: Sender2016, Li2014, Schmidt2016, Mass spec data on ATP synthase

The physical limits to bacterial growth: PowerPoint Presentation

Papers: An obsession with dN/dt (Neidhardt1999), Stouthamer1973VanOijen2006

Matlab tutorial: 3

Homework 1 answer key

1/26

Bacterial Growth: Simulations, analyzing movies of growing colonies and fitting our data

 

Simulating bacterial growth: Matlab code

Analyzing movies of growing bacteria: Microscopy images of growing bacteria, Matlab code V1

1/31

Flies by the Numbers: The physical limits to DNA replication in development

Homework 1 due

Homework 2 out, due 2/7: Sturtevant1913, Gregor2007a, Gregor2007b

Analyzing movies of growing bacteria: Matlab code V2

Flies by the Numbers: PowerPoint Presentation

Recombination and the first mapping of a chromosome: Sturtevant1913.

Matlab tutorial: 4 

Homework 2 answer key

2/2

Flies by the Numbers: The physical limits to transcription in development

Transcriptional elongation in flies: Data; Matlab code

2/7

Diffusion: Axonal transport and deriving the diffusion equation

Homework 2 due (send abstract for estimate over email to Hernan and Simon)

Diffusion: PowerPoint Presentation

2/9

Diffusion: Numerical simulations

Homework 3 out, due 2/21: Klumpp2013

Homework 3 solutions

2/14

Diffusion to capture and the physical limits to binding rates

Matlab code: Simulating diffusion

2/16

Regulatory biology and the constitutive promoter, Part I: Phase diagrams and solving for mean mRNA levels

Monod1949Zenklusen2008

Matlab code: Dynamics of the constitutive promoter

The constitutive promoter: PowerPoint slides

2/21

Regulatory biology and the constitutive promoter, Part II: Master equations and transcriptional noise, a numerical approach

Homework 3 due

2/23

Regulatory biology and the constitutive promoter, Part III: Master equations and transcriptional noise, an analytical approach

Presentation of first estimate (1/4 of the class)

Homework 4 out, due 3/2: Taniguchi2010

Solving the master equation for the constitutive promoter: Matlab code

Clarke1946: Flying-bomb attacks on London and the Poisson distribution

Jones2014

Homework 4 solutions

2/28

Presentation of first estimate (1/2 of the class)

 

3/2

Presentation of first estimate (1/4 of the class)

Regulatory biology: Simple repression, Part I

Homework 4 due

3/7

Regulatory biology: Simple repression, Part II

Homework 5 out, due 3/14: Voltage-gated ion channel data and paper (Keller1986)A First Exposure to Statistical Mechanics for Life Scientists (Garcia2007b).

3/9

Regulatory biology: Simple repression, Part III

Measuring gene expression in bacteria: Theoretical predictionSample data setFull data set, First version of image analysis code, Final version of image analysis code

Simple repression: Powerpoint Presentation

3/14

Image analysis and discussion with Simon

Homework 5 due, Homework 5 solutions

3/16

Binding problems in biology: Cooperativity, the MWC model, and ion channels

Homework 6 out, due 3/23: Garcia2011c

PBoC problem 4.1 and table 4.1

Oxygen binding and dimoglobin: Matlab code, Powerpoint Slides

Rossi-Fanelli1958data extracted using DigitizeIt

3/21

177 LSA

Developmental patterning: The French Flag model and how to make morphogen gradients

Install LapseIt on your iPhone, Android phone, or iPad. Bring it, together with a charger, to class.

Papers: Testing the French Flag model (Driever1989 and Liu2013); measuring Bicoid degradation (Drocco2011), diffusion (Abu-Arish2011), bicoid localization (Little2011), and translation (Petkova2014)

Powerpoint slides.

3/23

Developmental patterning: Testing the French Flag model

Homework 6 due, Homework 6 solutions

Homework 7 out, due 4/6: Gregor2007b data

Testing the French Flag model: Snapshots of developing fly embryos, Matlab code 

4/4

A probabilistic view of biology, Part I: Carboxysome partitioning

Coin flips and carboxysomes: Matlab code, Powerpoint slides

4/6

A probabilistic view of biology, Part II: Carboxysome partitioning and using fluctuations to count molecules

Homework 7 due, Homework 7 solutions

4/11

Evolution by the numbers, Part I: Genetic drift and the random forces that drive evolution

Dobzhansky1973

Genetic drift: Buri1956, Matlab code, Powerpoint slides

Homework 8 out, due 4/25: Rosenfeld2005, Buri data

4/13

Evolution by the numbers, Part II: Genetic drift and the random forces that drive evolution

The Wright-Fisher model of genetic drift: Matlab code

4/18

Presentation of second estimate (first half of the class)

Bring a smartphone or computer to fill out the offical course survey as well as Hernan's survey 

4/20

Presentation of second estimate (second half of the class) 

 

4/25

A dynamical view of biology: Genetic switches

Homework 8 due, Homework 8 solutions

Homework 9 out, due 5/8 at 10am in 505 LSA: Eden2011 (SI), Abouchar2014 (SI), Garcia-Bellido1979. Note that this homework is optional and only for extra credit. It is longer and harder than usual, and will be worth 200% of a regular homework. If you do it, will only take it into account if it improves your grade.

Genetic switches: Gardner2000, Laslo2006, Matlab code, Powerpoint slides

Homework 9 solutions

4/27

Biological specificity: Kinetic proofreading

Bio2010 report and summary

Gunawardena2014: Models in biology: `accurate descriptions of our pathetic thinking'

 

 

 

 

Matlab tutorials: We will assume no previous Matlab experience. These are small tutorials that introduce the different concepts we'll use in each class.

  1. Variable and arrays, and plotting.
  2. For-loops.
  3. Loading and displaying images (sample image).
  4. If-statements.

 

If you want to go beyond our introductory Matlab tutorials, here are some other great sources: 

 

 Bibliography:

  • Phillips, R., et al. (2013). Physical Biology of the Cell, 2nd Edition. New York, Garland Science.
  • Alberts, B. (2015). Molecular Biology of the Cell. New York, NY, Garland Science.
  • Milo, R. and Phillips, R. (to be published in 2016, can be downloaded from http://book.bionumbers.org/). Cell Biology by the Numbers. New York, NY, Garland Science.
  • Mahajan, S. (2010). Street-Fighting Mathematics: The Art of Educated Guessing and Opportunistic Problem Solving. MIT Press (2010).
  • Weinstein, L. and Adam, J.A. (2008). Guesstimation: Solving the World's Problems on the Back of a Cocktail Napkin. Princeton University Press.
Semester: 
Spring 2017
Tuesday, January 17, 2017