MCB137L / MCB237L: Physical Biology of the Cell

Hernan G. Garcia

Spring 2020

Introduction
Biology is being revolutionized by new experimental techniques that have
made it possible to quantitatively query the inner workings of molecules,
cells and multicellular organisms in ways that were previously unimaginable.
The objective of this course is to respond to this deluge of quantitative data
through quantitative models and the use of biological numeracy. The course
will explore the description of a broad array of topics from modern biology
using the language of physics and mathematics. One style of thinking we
will emphasize imagines the kinds of simple calculations that one can do
with a stick in the sand.
We will draw examples from broad swaths of modern biology from our
department and beyond including cell biology (signaling and regulation,
cell motility), physiology (metabolism, swimming), developmental biology
(patterning of body plans, how size and number of organelles and tissues
are controlled), neuroscience (action potentials and ion channel gating) and
evolution (population genetics) 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 course 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 future
research.

When and where

Lecture: Tuesday and Thursday, 3:30pm – 5:00pm, 20 Barrows

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Discussion section I: Friday, 12:00pm – 1:00pm, 70 Evans
Discussion section II: Friday, 1:00pm – 2:00pm, 9 Evans

Instructor and GSI

Instructor:
• Hernan Garcia (hggarcia@berkeley.edu)
• Office hours: Wednesdays, 3pm – 4pm, 505 LSA
GSI:
• Yang Joon Kim (yjkim90@berkeley.edu)
• Office hours: Tuesdays, 5pm – 6pm, 105 GPB
GSI:
• Jiaxi (Jake) Zhao (jiaxi.zhao@berkeley.edu)
• Office hours: Wednesdays, 11am – 12pm, 349 LSA

NOTE: For transparency, rather than emailing Hernan, Yang Joon

or Jake, we encourage you to message us through the course’s
Piazza website about any questions regarding homeworks and class
logistics.

Course structure
The class as a whole (approximately 50 students) will meet twice a week for
one hour and a half. This time will be devoted to lectures, discussions and
hands-on activities including Python exercises. Further, the class will be
split into weekly one-hour lab sessions. During these lab sessions, students
will work closely with the GSIs to implement the concepts they learned in
class in the context of different biological problems. Homework assignments
will be given every week and will represent 75% of the final grade. Twice
during the semester, students will prepare a project. The first project will
be a written assignment, while the second project will be presented in class.
These projects will represent 25% of the final grade.
For undergraduate students (MCB137L), the projects will consist on
carrying out an estimate on a biological phenomenon of interest following
the style presented in class. These presentations will be five minutes long.

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 For graduate students (MCB237L) the project will consist on presenting
a theoretical model developed in a recent paper of their choosing to the
class. These presentations will be ten minutes long.

Tentative syllabus
• Lectures 1 – 2: A feeling for the numbers in biology

– Street-Fighting Mathematics: Order-of-magnitude estimates as a

tool for discovery in the living world.
– What sets the scale of things?
– Biological time scales.

• Lectures 3 – 5: An obsession with dN/dt - Bacterial growth

– The physical limits to bacterial growth.

– Solving the exponential growth equation and testing it using im-
age analysis.

• Lectures 6 – 9: Diffusion, the null hypothesis of biological dynamics

– Diffusion and axonal transport.

– FRAP: Measuring diffusion using photobleaching.
– A universal diffusion speed limit for enzyme catalysis and other
reactions.

• Lecture 10: Biological numeracy

– Order of magnitude estimates.

– Astronomical numbers in biology.
– Dimensionless numbers in biology.
– Dimensional analysis.

• Lectures 11 – 12: Probability as the quantitative language of biology

– The binomial distribution: Coin flips, carboxysome partitioning

and calibrating fluorescent protein counts.
– The Poisson distribution: Bombs over London and sequencing
the human genome.

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 – The exponential distribution: Waiting times for photobleaching
and ion channel dynamics. The Boltzmann distribution and sta-
tistical mechanics.

• Lectures 13 – 14: Biological length control

– Mechanics of biological polymers.

– Cytoskeletal filament length distributions.

• Lectures 15 – 17: Regulatory biology

– Ion channels and two-state systems.

– The constitutive promoter.

• Lecture 18 – 20: A life-or-death decision: The Lambda switch

– Cooperativity and the generation of biological sharpness.

– A dynamical systems view of the Lambda switch.

• Lectures 21 – 24: Phase transitions in biology.

• Lectures 25 – 26: Biological specificity: Kinetic proofreading.

• Lectures 27 – 28: Second project presentations.

Required bibliography
• Phillips, R. et al. (2012). Physical Biology of the Cell, 2nd Edition.
Garland Science.

– Our course will be loosely based on this textbook. Many of the

assigned problems will come from it.

Suggested reading
• Kinder, J. and Nelson P. (2018). A Student’s Guide to Python for
Physical Modeling: Updated Edition. Princeton University Press.

– This book is a great introduction to programming in Python. It

could be useful reference material throughout the semester.

• Alberts, B. et al. (2014). Molecular Biology of the Cell. W. W. Norton

& Company.

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 – This book will be particularly useful for those needing a refresher
of biology.

• Milo, R. and Phillips, R. (2015). Cell Biology by the Numbers. Gar-

land Science.

– This book, together with its companion BioNumbers website, has

become the reference source for biological numeracy. The book
can also be downloaded from book.bionumbers.org.

• Mahajan, S. (2010). Street-Fighting Mathematics: The Art of Edu-

cated Guessing and Opportunistic Problem Solving. MIT Press.

• Weinstein, L. and Adam, J.A. (2008). Guesstimation: Solving the

World’s Problems on the Back of a Cocktail Napkin. Princeton Uni-
versity Press.

– These two books are fantastic resources for those wanting to learn
more about estimation writ large.

Course policy and suggestions

• Attending class and office hours:

– If you miss class, it is your responsibility to get notes from one

of your classmates. You cannot expect the instructor or GSI to
redo the lecture during office hours.
– Being able to attend office hours are a key to success. If you
cannot attend any of the three offered office hours, you might
want to reconsider taking this course.

• Homework assignments:

– Homeworks are due at the beginning of class one week after they
are posted.
– Homeworks should be submitted through GradeScope as described
in the course website. Any other form of homework submission
will not be accepted.
– No late homeworks. Time management is key. Start to work on
your homework assignments early and make use of office hours
and our availability over Piazza.

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 – It is important to describe your reasoning. Just writing an equa-
tion or drawing a plot does not constitute a satisfactory answer
to a homework problem.
– All plots in the homeworks need to have labeled axes.
– All code used needs to be submitted through GradeScope by the
homework due date.
– You can work in groups, but the answers should be your own.
This includes the code!

• Grading:

– Regrading is done only until a week after the homework solutions

are posted.
– If you ask us to regrade an answer in a homework assignment,
we reserve the right to regrade all the answers it that homework
assignment.
– Your two worst scoring homeworks will not be considered for the
final grade.
– We do not grade on a curve or anything like that. The grading
scale we will used is shown below.

Letter Percentage
A 94 – 100
A- 90 – 93
B+ 87 – 89
B 84 – 86
B- 80 – 83
C+ 77 – 79
C 74 – 76
C- 70 – 73
D+ 67 – 69
D 64 – 66
D- 60 – 63
F 0 – 65