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20.320 Biomolecular Kinetics and Cell Dynamics

Spring 2006

Michaelis-Menten plot.This plot of velocity vs. substrate concentration is based on the Michaelis-Menten equation. The Michaelis-Menten constant, KM, is the substrate concentration at which the enzyme reaction proceeds at half the maximum velocity. (Figure by MIT OCW.)

Course Highlights

This course features a full set of assignments.

Course Description

This class covers analysis of kinetics and dynamics of molecular and cellular processes across a hierarchy of scales, including intracellular, extracellular, and cell population levels; a spectrum of biotechnology applications are also taken into consideration. Topics include gene regulation networks; nucleic acid hybridization; signal transduction pathways; and cell populations in tissues and bioreactors. Emphasis is placed on experimental methods, quantitative analysis, and computational modeling.

Technical Requirements

Special software is required to use some of the files in this course: .m.





Syllabus

Amazon logo Help support MIT OpenCourseWare by shopping at Amazon.com! MIT OpenCourseWare offers direct links to Amazon.com to purchase the books cited in this course. Click on the Amazon logo to the left of any citation and purchase the book from Amazon.com, and MIT OpenCourseWare will receive up to 10% of all purchases you make. Your support will enable MIT to continue offering open access to MIT courses.


Subject Description

Our objective in this subject is to have you successfully learn the following:



Background

You will be most effectively prepared to take this subject if you have previously taken the following subjects:

  1. 5.07 (Biological Chemistry I) or 7.05 (General Biochemistry);
  2. 18.03 (Differential Equations);
  3. 20.011J (Statistical Mechanics of Biological Systems).


Homework, Exams, and Grading

Homework sets will be assigned on a weekly basis and must be turned in on the due date to the designated box. No late homeworks will be accepted, no exceptions. The lowest homework grade will be dropped at the end of the term. Working together on problem sets is acceptable, but each student is expected to turn in his/her own work. Names of people working together must be written on each assignment.

There will be 3 exams, each covering approximately 1/3 of the subject material periodically across the Semester. Final grades will be based on the following distribution:


ACTIVITIESPERCENTAGES
Exam 120%
Exam 220%
Exam 320%
Homework40%





Textbooks

Amazon logo Lauffenburger, Douglas A., and Jennifer Linderman. Models for Binding, Trafficking, and Signaling. New York, NY: Oxford University Press, 1995. ISBN: 9780195106633.

Tidor, Bruce, and K. Dane Wittrup. Biological Kinetics.





Calendar

The calendar below provides information on the course's lecture (L) and recitation (R) sessions.

DAL: Prof. Douglas Lauffenburger
FMW: Prof. Forest White
KA: Kathyryn Armstrong
SW: Shan Wu
CR: Craig Rothman


SES #INSTRUCTORSTOPICSKEY DATES
L1FMWIntroduction - 20, 20.320, Biology, Mechanisms, and Modeling Protein Interactions
R1KA/SW/CRRecitation 1
L2FMWProtein Interactions II

Thermodynamics of Monovalent Interactions
Problem set 1 assigned
L3FMWMonovalent Interactions
R2Recitation 2
L4FMWFractional SaturationProblem set 1 due

Problem set 2 assigned
L5FMWMeasurement Techniques for Kd
R3KA/SW/CRRecitation 3
L6FMWPerturbations to Monovalent InteractionsProblem set 2 due

Problem set 3 assigned
L7FMWPerturbations II - Solution Effects
R4Recitation 4
L8FMWMultivalent BindingProblem set 3 due

Problem set 4 assigned
L9FMWCooperativity
R5Recitation 5
L10FMWAvidity and Effective ConcentrationProblem set 4 due
R6CR/SWRecitation 6
FMWExam 1 - Monovalent Binding, Measurement, Perturbations, Multivalent Binding, Cooperativity
L11FMWEnzyme Kinetics I
L12FMWEnzyme Kinetics II
R7Recitation 7
R8Recitation 8
L13DALEnzyme InhibitorsProblem set 5 assigned
L14DALIntegrating Pathways Into Networks
R9Recitation 9
L15DALLigand-Receptor InteractionsProblem set 5 due

Problem set 6 assigned
L16DALEndocytic Trafficking I
R10Recitation 10
R11CR/SWRecitation 11Problem set 6 due
DAL/FMWExam 2 - Avidity, Enzymes, and Networks
L17DALEndocytic Trafficking IIProblem set 7 assigned
L18DALBiomolecular Reactions in Context of Transport
R12Recitation 12
L19DALFundamentals of Molecular TransportProblem set 7 due

Problem set 8 assigned
L20DALReaction Terms and Approximations
R13Recitation 13
L21DALMacroscopic and Microscopic Effects of DiffusionProblem set 8 due

Problem set 9 assigned (ungraded)
L22DALAutocrine/Paracrine Cell-cell Communication
R14Recitation 14
L23DALCell Population Dynamics I: Cell Growth, Death, Differentiation, and Product Synthesis
L24DALCell Population Dynamics II: Application to Tissues and Bioreactors
DALExam 3 - Test Accumulated Knowledge (Emphasis on Mechanisms Underlying Biomolecular Systems)




Readings

Amazon logo Help support MIT OpenCourseWare by shopping at Amazon.com! MIT OpenCourseWare offers direct links to Amazon.com to purchase the books cited in this course. Click on the Amazon logo to the left of any citation and purchase the book from Amazon.com, and MIT OpenCourseWare will receive up to 10% of all purchases you make. Your support will enable MIT to continue offering open access to MIT courses.


Instructors

DAL: Prof. Douglas Lauffenburger
FMW: Prof. Forest White
KA: Kathyryn Armstrong
SW: Shan Wu
CR: Craig Rothman



Textbooks

[W&T] Tidor, Bruce, and K. Dane Wittrup. Biological Kinetics.

[L&L] Amazon logo Lauffenburger, Douglas A., and Jennifer Linderman. Models for Binding, Trafficking, and Signaling. New York, NY: Oxford University Press, 1996. ISBN: 9780195106633.


SES #INSTRUCTORSTOPICSREADINGS
L1FMWIntroduction - 20, 20.320, Biology, Mechanisms, and Modeling Protein InteractionsW&T. Chapter 2.
R1KA/SW/CRRecitation 1
L2FMWProtein Interactions II

Thermodynamics of Monovalent Interactions
W&T. Chapter 2, 2.5.2.
L3FMWMonovalent InteractionsW&T. Chapter 3.
R2Recitation 2
L4FMWFractional SaturationW&T. Chapter 3.1-3.2.
L5FMWMeasurement Techniques for Kd
R3KA/SW/CRRecitation 3
L6FMWPerturbations to Monovalent Interactions
L7FMWPerturbations II - Solution Effects
R4Recitation 4
L8FMWMultivalent BindingW&T. Chapter 3.3.
L9FMWCooperativityW&T. Chapter 3.3.2.
R5Recitation 5
L10FMWAvidity and Effective ConcentrationW&T. Chapter 3.3.2.
R6CR/SWRecitation 6
FMWExam 1 - Monovalent Binding, Measurement, Perturbations, Multivalent Binding, Cooperativity
L11FMWEnzyme Kinetics I
L12FMWEnzyme Kinetics II
R7Recitation 7
R8Recitation 8
L13DALEnzyme Inhibitors
L14DALIntegrating Pathways Into Networks
R9Recitation 9
L15DALLigand-Receptor Interactions
L16DALEndocytic Trafficking IL&L. Chapter 3.
R10Recitation 10
R11CR/SWRecitation 11
DAL/FMWExam 2 - Avidity, Enzymes, and Networks
L17DALEndocytic Trafficking IIL&L. Chapter 6.1.3b.
L18DALBiomolecular Reactions in Context of Transport
R12Recitation 12
L19DALFundamentals of Molecular Transport
L20DALReaction Terms and Approximations
R13Recitation 13
L21DALMacroscopic and Microscopic Effects of Diffusion
L22DALAutocrine/Paracrine Cell-cell CommunicationL&L. Chapter 6.1.3c.
R14Recitation 14
L23DALCell Population Dynamics I: Cell Growth, Death, Differentiation, and Product Synthesis
L24DALCell Population Dynamics II: Application to Tissues and Bioreactors
DALExam 3 - Test Accumulated Knowledge (Emphasis on Mechanisms Underlying Biomolecular Systems)




Recitations

This section contains documents created from scanned original files, which are inaccessible to screen reader software. A "#" symbol is used to denote such documents.


SES #HANDOUTS
R1Ligand Activated Signaling Cascades (PDF)#
R2General Concepts (PDF)
R4Problems (PDF)#, Solutions (PDF)#
R5Problems (PDF)#, Solutions (PDF)#
R12Problems (PDF), Solutions (PDF)




Assignments

Special software is required to use some of the files in this section: .m. This section contains documents created from scanned original files, which are inaccessible to screen reader software. A "#" symbol is used to denote such documents.


ASSIGNMENTSSOLUTIONSSUPPORTING FILES
Problem Set 1 (PDF)(PDF)#
Problem Set 2 (PDF)(PDF)#pset2_data.htm (HTM)
Problem Set 3 (PDF)(PDF)#hw3.m (M)

C_function.m (M)
Problem Set 4 (PDF)(PDF)#pset4_data.htm (HTM)
Problem Set 5 (PDF)(PDF)#
Problem Set 6 (PDF)(PDF)pset6_matlab.m (M)

KinaseCascade.m (M)

Ferrell, J. E., Jr. "Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs." Trends Biochem Sci 21, no. 12 (December 1996): 460-6.

Kuhl, P. R., and L. G. Griffith-Cima. "Tethered epidermal growth factor as a paradigm for growth factor-induced stimulation from the solid phase." Nat Med 2, no. 9 (September 1996): 1022-7.
Problem Set 7 (PDF)(PDF)gross_lodish.m (M)

pset7_matlab.m (M)

Gross, A. W., and H. F. Lodish. "Cellular trafficking and degradation of erythropoietin and novel erythropoiesis stimulating protein (NESP)." J Biol Chem 281, no. 4 (January 27, 2006): 2024-32. Epub (November 11, 2005).
Problem Set 8 (PDF)(PDF)#myfun.m (M)

demo_fsolve.m (M)

pset8_matlab.m (M)
Problem Set 9 (PDF)(PDF)Sarkar, C. A., and D. A. Lauffenburger. "Cell-level pharmacokinetic model of granulocyte colony-stimulating factor: implications for ligand lifetime and potency in vivo." Mol Pharmacol 63, no. 1 (January 2003): 147-58.




Exams

This section contains documents created from scanned original files and other documents that could not be made accessible to screen reader software. A "#" symbol is used to denote such documents.


PRACTICE PROBLEMSSOLUTIONS
Practice for Exam 1 (PDF)
Practice for Exam 2 (PDF)(PDF)
Practice for Exam 3 (PDF)(PDF)#





Exam Solutions

Exam 1 Solution (PDF)#

Exam 2 Solution (PDF)#

Exam 3 Solution (PDF)#





Study Materials

Special software is required to use some of the files in this section: .m. This section contains documents created from scanned original files, which are inaccessible to screen reader software. A "#" symbol is used to denote such documents.



MATLAB® Basics

MATLAB® Reference Sheet (PDF)

MATLAB® Tutorial: Basics (PDF)

MATLAB® Tutorial: Basics - Solutions (PDF)

Code for Additional Exercise 1, add_ex1.m (M)

Code for Additional Exercise 2, add_ex2.m (M)

Code for Additional Exercise 3, add_ex3.m (M)



MATLAB®: ODE Solving and Nlinfit

MATLAB® Tutorial 2: Slides and Notes (PDF)#

Code for 2nd MATLAB® Tutorial, ODEexample.m (M)

Function Code for ODEexample.m, ODEexample_equations.m (M)

Code from 2nd MATLAB® Tutorial for Nlinfit, SPR_leastSquares.m (M)

SPR_function.m (M)

The Parameters and ICs you Need to do Exercise 1, ex1.m (M)

Solution to Exercise 1, ex1_solution.m (M)

Function File for Exercise 1 (Part of the Solution), ex1_equations.m (M)

The Data you Need to do Exercise 2, ex2.m (M)

Solution to Exercise 2, ex2_solution.m (M)

Function File for Nlinfit in Exercise 2, with PFOA (Part of the Solution Function file, ex2_function_PFOA.m (M)

Function File for for Nlinfit in Exercise 2, without PFOA (Part of the Solution), ex2_function.m (M)




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