MCDB 4550/5550 (2016)

Instructors

Thomas Perkins, tperkins@jila.colorado.edu
Meredith Betterton, meredith.betterton@colorado.edu

Description

Straightforward application of classical Newtonian physics does a poor job of providing insight into biological processes. This course will develop a simple description of the biophysics governing the motion of molecules inside of cells. This course starts with an overview of the physics that governs molecular motors, the cytoskeleton and, more generally, proteins inside of the cell as well as a review of single molecule techniques. It then moves into application of these concepts in a cellular context, focusing on chromosome separation. Topics covered will include diffusion, entropy, chemical energy, polymers, intermolecular forces, cytoskeleton, molecular motors, and single-molecule techniques. Each student will give two oral presentations on journal articles. Problem sets will provide a quantitative understanding of the topics discussed. A final paper will be required that addresses a critical question in biophysics and/or outlines a proposed experimental approach to answer the question, or a design project to address a biomedical application.

Prereq, CHEM 1131 or 1171, physics 2010, 2020, MCDB 3120, or instructor consent.
Recommended prereq., Math 1300 and/or CHEM 3311. Same as MCDB 5550.

Grade determination:
15%    Participation in class discussion
30%    Oral presentation
25%    Problem sets
30%    Final paper

Presentations:

Each student will give two oral presentations, in teams if necessary, on the primary literature reading assignments. These presentations will be followed by a discussion led by the presenting student(s) to critically analyze the reading material and to review what students have learned from the presentation and the reading material.

Paper:

Each student will write a 6-8 page paper (10-12 for graduate students) that either proposes (i) an experiment using biophysical techniques with quantitative estimates, (ii) a critique of a set of papers, (iii) a design project (upon approval by an instructor) or (iv) a topic mutually agreed upon between the student and an instructor.

Texts (required for course):

Mechanics of Motor Proteins and the Cytoskeleton by Jonathon Howard, 2001

Texts (supplementary information):

  • Molecular Biology of the Cell  54th Edition, silver cover),  By Alberts, et al.,  (any addition)

      A good, encyclopedic biology text book. Very good for learning vocabulary but a little dry

  • Biochemistry  (7th Edition, grey cover), By Berg, Tymoczko,  Stryer, &, 2010 or equivalent

  • Physical Biology of the Cell, 2nd Edition, Phillips et al. (Excellent but more advanced)

Office Hours

Time: Wednesday 2-3 pm
Office: JILA A503 (weeks that Perkins is lecturing)
Or        Duane F629 (weeks that Betterton is lecturing)   

 

Week

Tuesday

Thursday

1: 1/12-14

Introduction
Reading: Chapter 1

Random walks & mechanical forces
Reading: Chapter 2

2: 1/19-21

Mass, stiffness & damping of a protein
Reading: Chapter 3

Single Molecule Techniques: Optical Traps and applications to molecular motors (Perkins, 2009, & Perkins, 2014)

Assignment #1 due

3: 1/26-28

Cytoskeletal filaments

Reading: Chapter 7

Motor proteins

Reading: Chapters 12-13

Assignment #2 due

4:  2/2-4

Thermal forces & diffusion
Reading: Chapter 4

Chemical forces
Reading: Chapter 5

Assignment #3 due

5:  2/9-11

Polymer mechanics
Reading: Chapter 6

Group 1 presentation: Hua et al., Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements

Assignment #4 due

6:   2/16-18

Single Molecule Techniques: Fluorescence

nmeth.f.233

nmeth.f.235

Group 2 Presentation: Asbury et al, Kinesin moves by an asymmetric hand over hand mechanism

Assignment #5 due

7:   2/23-25

Single molecule techniques: Atomic Force microscopy

(Neuman et al, 2008),

Group 3 Presentation: Yildz et al Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization

Assignment #6 due

8: 3/1-3

Cytoskeletal filament mechanics and polymerization

Reading: Chapters 8-9

Group 4 Presentation: Wuite et al.Single-molecule studies of the effect of template tension on T7 DNA polymerase activity

Assignment #7 due

9: 3/8-10

Group 5 Presentation: Abbondanzieri, et al.,Direct Observation of base-pair stepping by RNA Polymerase

Group 6 Presentation: Hamdan et al., Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis.

Assignment #8 due

10: 3/15-17

Guest Lecture: Dick McIntosh

(Asbury et al) Kinetochores’ gripping feat: conformational wave of biased diffusion

Group 1: Wang & Ha, Defining single molecular forces required to activate integrin and notch signaling

Assignment #9 due

3/22-24

Spring Break

Spring Break

11:  3/29 -3/31

Polymerization

Reading: Chapters 9-10

Group 2 Presentation: Dogertom et al., Measurements of the force-velocity relation for growing microtubules

12: 4/5-7

Active polymerization

Reading: Chapters 11

Group 3 Presentation: Laan et al., Cortical Dynein Controls Microtubule Dynamics to Generate Pulling Forces that Position Microtubule Asters

Assignment #11 due

13:  4/12-14

ATP Hydrolysis

Reading Chap 14

Group 4 Presentation: Akiyoshi et al., Tension directly stabilizes reconstituted kinetochore-MT attachments.

14:  4/19-21

Steps, forces, and motility models

Reading: Chapter 15-16

Group 5 Presentation: Wan et al., Protein Architecture of the Human Kinetochore Microtubule Attachment Site

Assignment #12 due

15:  4/26-28

Group 6 Presentation: Dumont et al, Deformations within moving kinetochores reveal different sites of active and passive force generation

Summary

PERKINS LECTURES IN TAN

BETTERTON LECTURES IN GREEN

 

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