MCDB 4550/5550 Syllabus: Cells, Molecules and Tissues: A Biophysical Approach

Crosslisted as: PHYS 4550/5550
Instructor: Thomas Perkins, tperkins@colorado.edu

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. 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, typically in teams, 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.

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 the instructor) or (iv) a topic mutually agreed upon between the student and the instructor. Paper is due May 2nd by 5 PM. 

Texts (required for course):

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

Texts (supplementary information):

  • Molecular Biology of the Cell (any edition),  By Alberts, et al.,
    --A good, encyclopedic biology text book. Very good for learning vocabulary but a little dry
  • Biochemistry  (any edition), By Berg, Tymoczko,  Stryer, 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

Syllabus

Week

Tuesday

Thursday

1: 1/16-18

Introduction
Reading: Chapter 1

Random walks & mechanical forces
Reading: Chapter 2

2: 1/23-25

Cytoskeletal filaments and their mechanics
Reading: Chapter 7,8

Motor proteins
Reading: Chapter 12,13

PS #1 due Feb. 1

3: 1/30-2/1

Single-molecule techniques: Atomic force microscopy (Neuman et al, 2008),

Guest lecture: Prof. Dick McIntosh (MCDB)

4:  2/6-8

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

Thermal forces & diffusion
Reading: Chapter 4

PS#2 due Feb 15

5:  2/13-15

Tips on giving a scientific presentation.

Single-Molecule Techniques: Fluorescence

PS #3 due Feb 22

6:   2/20-22

Single-molecule techniques: Optical traps and applications to molecular motors (Perkins, 2009, & Perkins, 2014)

Presentation Example:: Hua et al., Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements

PS #4 Due Feb 29

7:   2/27-29

Chemical forces
Reading: Chapter 5

PS #5 Due March 5

Group 1 Presentation: Asbury et al., Kinesin moves by an asymmetric hand over hand mechanism

8: 3/5-7

Group 2 Presentation: Yildiz et al., Kinesin walks hand over hand

Group 3 Presentation: Wolff et al, MINFLUX dissects the unimpeded walking of kinesin-1

9: 3/12-14

Nanomechanics of DNA and nucleic acid hairpins
Reading: Chapter 6

Group 4 Presentation: Wang and Ha, DNA-based digital tension probes reveal integrin forces during early cell adhesion

10: 3/19-21

Single-molecule technique: mass photometry

Group 5 Presentation: Zhang, et al., DNA-based digital tension probes reveal integrin forces during early cell adhesion 

3/26-28

Spring Break

Spring Break

11:  4/2-4

Polymerization
Reading: Chapter 9,10

Single-molecule technique: magnetic tweezers

12: 4/9-11

Active polymerization
Reading: Chapter 11

ATP  hydrolysis, steps and forces
Reading: Chapter 14,15

13:  4/16-18

Group 1 Presentation: Newton et al., DNA stretching induces Cas9 off-target activity

Group 2 Presentation: Kerssemakers et al, Assembly dynamics of microtubules at molecular resolution

14:  4/23-25

Group 3 Presentation: Asbury et al., Dam1 kinetochore complex harnesses microtubule dynamics to produce force and movement

Group 4 Presentation: LeBlanc et al., Type III secretion system effector proteins are mechanically labile

15:  4/30-5/2

Group 5 Presentation: Zhao & Woodside, Mechanical strength of RNA knots in Zika virus protects against cellular defenses

Summary:

Classroom Behavior

Students and faculty are responsible for maintaining an appropriate learning environment in all instructional settings, whether in person, remote, or online. Failure to adhere to such behavioral standards may be subject to discipline. Professional courtesy and sensitivity are especially important with respect to individuals and topics dealing with race, color, national origin, sex, pregnancy, age, disability, creed, religion, sexual orientation, gender identity, gender expression, veteran status, political affiliation, or political philosophy.

For more information, see the
classroom behavior policy, the Student Code of Conduct, and the Office of Institutional Equity and Compliance.

Requirements for Infectious Disease

Members of the CU Boulder community and visitors to campus must follow university, department, and building health and safety requirements and all applicable campus policies and public health guidelines to reduce the risk of spreading infectious diseases. If public health conditions require, the university may also invoke related requirements for student conduct and disability accommodation that will apply to this class.

If you feel ill and think you might have COVID-19 or if you have tested positive for COVID-19, please stay home and follow the guidance of the Centers for Disease Control and Prevention (CDC) for isolation and testing. If you have been in close contact with someone who has COVID-19 but do not have any symptoms and have not tested positive for COVID-19, you do not need to stay home but should follow the guidance of the CDC for masking and testing.

Accommodation for Disabilities, Temporary Medical Conditions, and Medical Isolation

If you qualify for accommodations because of a disability, please submit your accommodation letter from Disability Services to your faculty member in a timely manner so that your needs can be addressed.  Disability Services determines accommodations based on documented disabilities in the academic environment.  Information on requesting accommodations is located on the Disability Services website. Contact Disability Services at 303-492-8671 or dsinfo@colorado.edu  for further assistance.  If you have a temporary medical condition, see Temporary Medical Conditions on the Disability Services website.

If you have a required medical isolation for which you require adjustment, please contact Dr. Perkins by email.

Preferred Student Names and Pronouns

CU Boulder recognizes that students' legal information doesn't always align with how they identify. Students may update their preferred names and pronouns via the student portal; those preferred names and pronouns are listed on instructors' class rosters. In the absence of such updates, the name that appears on the class roster is the student's legal name.

Honor Code

All students enrolled in a University of Colorado Boulder course are responsible for knowing and adhering to the Honor Code. Violations of the Honor Code may include but are not limited to: plagiarism (including use of paper writing services or technology [such as essay bots]), cheating, fabrication, lying, bribery, threat, unauthorized access to academic materials, clicker fraud, submitting the same or similar work in more than one course without permission from all course instructors involved, and aiding academic dishonesty.

All incidents of academic misconduct will be reported to Student Conduct & Conflict Resolution: honor@colorado.edu, 303-492-5550. Students found responsible for violating the Honor Code will be assigned resolution outcomes from the Student Conduct & Conflict Resolution as well as be subject to academic sanctions from the faculty member. Visit Honor Code for more information on the academic integrity policy.

Sexual Misconduct, Discrimination, Harassment and/or Related Retaliation

CU Boulder is committed to fostering an inclusive and welcoming learning, working, and living environment. University policy prohibits protected-class discrimination and harassment, sexual misconduct (harassment, exploitation, and assault), intimate partner violence (dating or domestic violence), stalking, and related retaliation by or against members of our community on- and off-campus. These behaviors harm individuals and our community. The Office of Institutional Equity and Compliance (OIEC) addresses these concerns, and individuals who have been subjected to misconduct can contact OIEC at 303-492-2127 or email cureport@colorado.edu. Information about university policies, reporting options, and support resources can be found on the OIEC website.

Please know that faculty and graduate instructors must inform OIEC when they are made aware of incidents related to these policies regardless of when or where something occurred. This is to ensure that individuals impacted receive outreach from OIEC about resolution options and support resources. To learn more about reporting and support for a variety of concerns, visit the Don’t Ignore It page.

Religious Accommodations

Campus policy requires faculty to provide reasonable accommodations for students who, because of religious obligations, have conflicts with scheduled exams, assignments or required attendance. Please communicate the need for a religious accommodation in a timely manner. In this class, please contact Dr. Perkins at least 2 weeks ahead of the holiday.

See the campus policy regarding religious observances for full details.

Mental Health and Wellness

The University of Colorado Boulder is committed to the well-being of all students. If you are struggling with personal stressors, mental health or substance use concerns that are impacting academic or daily life, please contact Counseling and Psychiatric Services (CAPS) located in C4C or call (303) 492-2277, 24/7. 

Free and unlimited telehealth is also available through 
Academic Live Care. The Academic Live Care site also provides information about additional wellness services on campus that are available to students.