MCB137/237 - 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: Wednesdays 1:30pm to 2:30pm @ 501C LSA. Please, see announcement on Piazza for updated office hours.

Course GSI: Elizabeth Eck (eeck@berkeley.edu, Office hours: Mondays 11:00am to 12:00pm @ 349 LSA) & Gabriella Martini (martini@berkeley.edu, Office hours: Tuesdays 4:00pm to 5:00pm @ 349 LSA). 

Class materials:

Schedule: Class meets Tuesdays from 2-4 PM in 107 Genetics & Plant Biology Building and Thursdays from 2-4 PM in 103 Genetics & Plant Biology Building. There are no independent Discusison sections as Lectures, Labs and Discussions are integrated within the weekly lectures. 

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.

 

Lecture

Date Topics Materials

1

1/22

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

E. coli by the numbers

A feeling for the numbers: Powerpoint Presentation

Matlab tutorial: 1

Papers: Mathematics Is Biology’s Next Microscope, Only Better; Biology Is Mathematics’ Next Physics, Only Better (Cohen2004), Theory in Biology: Figure 1 or Figure7? (Phillips2015b), Distribution of biomass on Earth (Bar-ON2018 and SI) and Number of genes in human genome, The Tragic Matter (Schatz2003), Polymerases and the Replisome (Baker1998)

Reading material: PBoC chapters 1 through 3

Making simple plots: Matlab code (in class

2

1/24

Temporal scales in biology

Bacterial Growth: Simulations using the Euler method

Homework 1 out, due 1/31Sender2016Li2014

E. coli by the numbers - Bacterial growth: Powerpoint Presentation

Simulating bacterial growth: Matlab code (in class)

Papers: An obsession with dN/dt (Neidhardt1999)

Reading material: PBoC chapters 2 and 3

Matlab tutorials: 2 and 3

Homework 1 Solutions 

3

1/29

Bacterial Growth: Limits to bacterial growth, Part I

E. coli by the numbers - Limits to bacterial growth, Part I: Powerpoint Presentation

Papers: Stouthamer1973

Reading material: PBoC chapters 2 and 3

4

1/31

Bacterial Growth: Limits to bacterial growth, Part II

Homework 1 due

Homework 2 out, due 2/7: Schmidt2016Mass spec data on ATP synthase, Cai2006

E. coli by the numbers - Limits to bacterial growth: Part II: Powerpoint Presentation

Papers: VanOijen2006

Reading material: PBoC chapters 2 and 3, MBoC chapters XX (ATP Synthase, Mass spectrometry)

Homework 2 Solutions 

Homework 2 MATLAB Code 

5

2/5

Diffusion: Axonal transport and deriving the diffusion equation

 

Diffusion, Part I: Powerpoint Presentation

Papers: Lipps2011, Hochbaum2014, Droz1962, Cui2007, Morfini2011, Yildiz2003

Reading material: PBoC chapter 13

Matlab tutorial: 4 

6

2/7

Bacterial Growth: Analyzing movies of growing colonies and fitting data

Homework 2 due

Homework 3 out, due 2/14

Measuring bacterial growth using microscopy: Data, MatlabCode

Reading material: PBoC chapters 2 and 3

Homework 3 Solutions 

Homework 3 MATLAB Code - Bacterial Growth 

Homework 3 MATLAB Code - Diffusion

7

2/12

Diffusion: Solving the diffusion equation using coin flips

Diffusion by coin flips: Matlab code

Reading material: PBoC chapter 13

8

2/14

Diffusion and FRAP: Solving the diffusion equation using master equations, Part I

Homework 3 due (send abstract for estimate over email to Hernan, Gabriella and Liz)

Homework 4 out, due 2/21

Diffusion, Part II: Powerpoint Presentation

Homework 4 Solutions 

9

2/19

Diffusion and FRAP: Solving the diffusion equation using master equations, Part II

Diffusion, Part III: Powerpoint Presentation

Spread the butter for diffusion: Matlab code

10

2/21

Flies by the Numbers: The physical limits to DNA replication and transcription in development, Part I

Homework 4 due

Homework 5 out, due 2/28: Gregor2007aGregor2007b

Flies by the Numbers: Powerpoint Presentation

Recombination and the first mapping of a chromosome: Sturtevant1913.

Homework 5 Solutions 

Homework 5 MATLAB Code - FRAP

11

2/26

Flies by the Numbers: The physical limits to DNA replication and transcription in development, Part II

 

Transcriptional elongation in flies: Data and Matlab code

12

2/28

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

Dimensionless numbers and dimensional analysis

Homework 5 due

Homework 6 out, due 3/7: Abouchar2014 (SI), Garcia-Bellido1979.

The French Flag model: Powerpoint Slides

Papers: Testing the French Flag model (Driever1989 and 2013); measuring Bicoid degradation (Drocco2011), diffusion (Abu-Arish2011), bicoid localization (Little2011), and translation (Petkova2014)

Testing the French Flag model: Bicoid dosage mutant sample image, Bicoid dosage full data setMatlabCode

Homework 6 Solutions

13

3/5

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

Discussion: Thinking about concentrations and ATP in the cell

 

14

3/7

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

Homework 6 due

No homework this week - Time to work on your estimate vignettes (due 3/14)

Monod1949Zenklusen2008

Dynamics of the constitutive promoter: Matlab code

The constitutive promoter: Powerpoint Slides

15

3/12

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

Discussion: Diffusion estimates

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

Jones2014: Transcriptional noise in the lac operon

16

3/14

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

Estimate vignettes due (email them to Hernan, Gabriella and Liz)

Homework 7 out, due 3/21: Taniguchi2010Petkova2014Gunawardena2014 (Models in biology: `accurate descriptions of our pathetic thinking')

Solving the master equation for the constitutive promoter: Matlab code

Homework 7 Solutions 

Homework 7 MATLAB Code - Cephalic Furrow Position

17

3/19

Regulatory biology: Simple repression, Part I

Simple repression: Powerpoint Slides

Matlab: Plotting pbound for the constitutive promoter

18

3/21

Regulatory biology: Simple repression, Part II

 

Homework 7 due

Homework 8 out, due 4/4: A First Exposure to Statistical Mechanics for Life Scientists (Garcia2007b). Voltage-gated ion channel data and paper (Keller1986). Dissection of simple repression: Garcia2011c

Matlab: Sample microscopy images of bacteriaFull bacterial gene expression data set, Extractting fluorescence from bacterial cells

Homework 8 Solutions 

Homework 8 MATLAB Code - Filament Length

Homework 8 MATLAB Code - Ion Channel

19

4/2

The forces of evolution: Mutation - Luria-Delbruck, Part I

Nothing in biology makes sense except in the light of evolution: Dobzhansky1973

Luria-Delbruck experiment: Powerpoint SlidesLuria1943

Exploring the adaptive mutation hypothesis (Poisson distribution): Matlab code

20

4/4

The forces of evolution: Mutation - Luria-Delbruck, Part II

Homework 8 due

Homework 9 out, due 4/11

Simulating the Luria-Delbruck experiment: Matlab code

Homework 9 Solutions 

Homework 9 MATLAB Code - Taylor Expansion

Homework 9 MATLAB Code - Poisson Distribution

21

4/9

The forces of evolution: Genetic drift - Buri experiment, Part I

Genetic drift: Buri1956, Powerpoint Slides 

Simulating genetic drit by coin flips: Matlab code

22

4/11

The forces of evolution: Genetic drift - Buri experiment, Part II

 

Homework 9 due  (send abstract for estimate over email to Hernan, Gabriella and Liz)

Homework 10 out, due 4/18: Buri data

Genetic drift by spreading the butter: Matlab code

Homework 10 Solutions 

23

4/16

Study Hall to prepare for presentations  

24

4/18

Dynamical systems: A genetic switch, Part I

Homework 10 due

Homework 11 (extra credit) out, due 5/2


Genetic switches: Gardner2000, Laslo2006, PowerPoint Slides, Matlab code

 25

4/23  Dynamical systems: A genetic switch, Part II  

26

4/25 Physical Biology of the Cell

Bring a smartphone or computer to fill out the official course survey as well as Hernan's survey: Hernan's survey, Berkeley's survey

27

4/30

Presentations of second estimate (1/2 of the class)  

28

5/2 Presentations of second estimate (1/2 of the class) Homework 11 (extra credit) due

 

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. (PBoC)

Alberts, B. (2015). Molecular Biology of the Cell. New York, NY, Garland Science. (MBoC)

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.

 

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

Semester: 
Spring 2019
Tuesday, January 22, 2019