MCB137/237 Spring 2022

Physical Biology of the Cell

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 Python. 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.

The class as a whole will meet twice a week for one hour and a half - Tuesdays and Thursdays, 11am - 12:30pm. The first few lectures will be on Zoom at the address linked in the Syllabus section below, and in 219 Dwinelle once in-person classes resume. 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 assignment 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.

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. Attending class and office hours
If you miss classes, 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 to the GSIs in PDF form. 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.
It is important to describe your reasoning. Just writing an equation 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 GraceScope 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(distribution) or anything like that.
Title Due Date Required Materials Solutions
Homework 1 1/27 at 11:00 AM
Homework 2 2/03 at 11:00 AM
Homework 3 2/10 at 11:00 AM
Homework 4 2/17 at 11:00 AM
Homework 5 2/24 at 11:00 AM
First estimate (MCB137L) and model proposal (MCB237L) 3/3 at 11:00 AM
Homework 6 3/10 at 11:00 AM
Homework 7 3/17 at 11:00 AM
Homework 8 3/31 at 11:00 AM
Homework 9 4/7 at 11:00 AM
Homework 10 4/14 at 11:00 AM
Homework 11 (extra credit) 4/21 at 11:00 AM
Second estimate (MCB137L) and poster session (MCB237L) 4/28 at 11:00 AM

A pdf of the full course syllabus can be found here.

Number Date Topics Materials Discussion Videos
1 1/18 Lecture
  • 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?
  • The physical biology exam, Part 1.
2 1/20 Lecture
  • The physical biology exam, Part 2.
3 1/25 Lecture
  • The scale and scaling of cellular structures and processes, Part 1.
    • Nucleolus scaling in C. elegans.
    • Fitting data by eye with Python.
4 1/27 Lecture
  • The scale and scaling of cellular structures and processes, Part 2.
    • Surface to volume ratio and energy scaling in the cell.
    • Time scales in biology.
    • Exponential growth by pen and paper, and by simulation.
5 2/1 @ 219 Dwinelle
  • The scale and scaling of cellular structures and processes, Part 3.
    • Time scales in biology.
    • Exponential growth by pen and paper, and by simulation.
6 2/3 @ 219 Dwinelle
  • Diffusion, the null hypothesis of biological dynamics, Part I : Diffusion and Axonal Transport
  • Measuring bacterial growth using image analysis, Part II.
7 2/8 Lecture
  • Diffusion, the null hypothesis of biological dynamics, Part II. Diffusion using by coin flips
8 2/10 @ 219 Dwinelle
  • Diffusion, the null hypothesis of biological dynamics, Part III: Diffusion by Solving the Chemical Master Equation
  • Measuring bacterial growth using image analysis, Part III.
    • Least Squares Fitting
9 2/15 @ 219 Dwinelle
  • Biological Dynamics, Part I: The mean dynamics of the constitutive promoter
10 2/17 @ 219 Dwinelle
  • Biological Dynamics, Part II: The single-cell distribution of the constitutive promoter
11 2/22 @ 219 Dwinelle
  • Regulatory Biology and Statistical Mechanics: The Constitutive Promoter Revisited
12 2/24 @ 219 Dwinelle
  • Regulatory Biology and Statistical Mechanics: Simple Repression
13 3/1 @ 219 Dwinelle
  • Defiance Is the Secret of Life, Part I
    • Energy for fun and profit
    • Entropy maximization and the 2nd law of thermodynamics
14 3/3 @ 219 Dwinelle
  • Defiance Is the Secret of Life, Part II
    • Entropic forces: A DNA entropic spring
15 3/8 Lecture
  • Guest Lecturer: Rob Phillips
  • Defiance Is the Secret of Life, Part III
    • Biological batteries
    • Defying diffusion: The proton gradient battery
    • The chemical potential
16 3/10 Lecture
  • Guest Lecturer: Rob Phillips
  • Defiance Is the Secret of Life, Part IV
    • Getting energy out of concentration gradients: Symporters
17 3/15
  • Defiance Is the Secret of Life, Part V
    • Review of lectures 15 and 16
    • Phosphorylation and the ATP battery
18 3/17
  • Defiance Is the Secret of Life, Part VI
    • Defying specificity: Kinetic proofreading
19 3/29
  • Lecture cancelled
20 3/31 Lecture
  • Guest Lecturer: Rob Phillips
  • Molecular Switches:
    • Protein-protein cooperativity
    • The MWC model
  • A simple model of cytoskeletal growth, Part I
21 4/5 Lecture
  • Dynamical systems, Part I:
    • Mutual repression switches
    • Epidemiology: The SRI model and flattening the curve
22 4/7 Lecture
  • Dynamical systems, Part II:
    • Mutual repression switches
    • Epidemiology: The SRI model and flattening the curve
23 4/12
  • Divide and Conquer: Compartmentalization in Space and Time, Part I
    • Guest lecturers: Jane Kondev (Brandeis University) and Christina Hueschen (Stanford University)
    • Michealis-Menten enzyme kinetics
24 4/14
  • Divide and Conquer: Compartmentalization in Space and Time, Part II
    • Guest lecturers: Jane Kondev (Brandeis University) and Christina Hueschen (Stanford University)
    • Compartmentalization of enzymatic reactions in the carboxysome
25 4/19
  • Stochastic simulations:
    • The stochastic simulation protocol
    • Simulating stochastic mRNA production dynamics
  • Fill out course evaluations.
26 4/21
  • -"Class canceled"
27 4/26
  • Exit Talk: Breaking the Standard Model (of Embryonic Development)
  • Fill out course survey:
28 4/28 @ VLSB courtyard
  • MCB237L poster session and end-of-course party!