Course-Embedded Research in Bio 460: Physical Biology of the Cell Jennifer Klein, Assistant Professor

Biology Department

Spring, 2015

Physical Biology & Course-Embedded Undergraduate Research

Course Overview:

• Upper level elective in UW-La Crosse Biology; enrollment: Year 1, 4 students; Year 2, 8 students

• Interdisciplinary and focuses on questions relevant to cell and molecular biology, but leans heavily on the allied fields of chemistry, physics and mathematics in order to approach biological problems quantitatively

Course Aims:

• Foundational understanding of the physical properties of biological systems, from biomolecules to cells

• Introduce the techniques and approaches used by biophysicists, apply to an original, independent project

Course-Embedded Undergraduate Research Projects:

• Biophysics is unique among life sciences in that it is strictly quantitative—the aim is always to create a physical or quantitative model of a biological problem

• The most common way to model the molecular level is using classical mechanics (equations of motion and force)—this is an indispensible tool for molecular biophysicists, biochemists, and quantitative cell biologist to learn

• Students create original research proposals, REAL research component includes creating a computational model:

• Aim 1: Experimental: Physiological (human health)

• Aim 2: Experimental: Biochemistry or Molecular Biology

• Aim 3: Computational: Quantitative or physical model of molecular world (molecular dynamics)

Table 1. Course structure and timeline Weeks 1-7 Building foundational knowledge and skills in molecular biophysics

• Lecture: lectures focus on foundational biophysics theory and application

• Case studies: students learn how to use computation to visualize and simulate the molecular world to answer questions related to molecular shape, motion and change.

• Midterm exam: a week-long project that tests student’s fundamental physical understanding of molecules and ability to prepare and use quantitative models

Weeks 8-11

Practicing applying knowledge

• Literature Discussions: students will use guided inquiry to prepare for discussion and then present data from figures in class

• Formulate aims for an original research proposal: first steps toward research projects

• Computational Models: build initial computational models (protein in a cell-like environment) related to proposals

Weeks 12-14

Creating original works

• Literature Discussions: students choose and present papers related to their own projects

• Proposal Writing and Review: stepwise progress through writing (multiple peer and instructor reviews)

• Computational Models: bring protein models to “life” using simulation and supercomputing. Gather preliminary data for proposals.

Table 2. Course Activities and Assignments Case Studies Students work in and out of class through four computational biophysics case studies. Journal Articles Students have three opportunities to present figures from a journal article and to lead

discussion. Written Proposal Proposal assignment is a 8-week, progressive assignment:

• Literature/Grant Search & References • Hypothesis and Specific Aims • Outline of Approach/Methods • Significance/Introduction • Approach/Methods • Full research proposal • Peer-review and revision

Course-Embedded Research

• 10-nanosecond molecular dynamics simulation relating to research proposal

Midterm Exam & Primary Lit Exam

• Midterm tests student’s fundamental physical understanding of molecules and ability to prepare and use quantitative models.

• Primary literature exam that tests student’s ability to understand data from primary literature and to critically evaluate its interpretation.

Results: • Students report that they merely recognized most ideas and skills before taking the course

(blue bars). After taking the course (orange bars), students report that they could now discuss or respond to exam questions for all SLO’s represented in the survey.

• The largest learning gains occurred in the SLOs related to the CUR project (creating and using quantitative models)

• Student performance on direct measures of learning outcomes including exams (data not

shown) indicate that they have generally met learning goals, consistent with what they report

Figure. 2: Comparison of CURs that occurred in two upper level biology courses taught by the same instructor. Bio 460 is Physical Biology of the Cell, which included writing an original research proposal and carrying out novel molecular dynamics simulations of proteins for projects selected by students. Bio 436 is Molecular Biology Lab, which included carrying out mutagenesis, cloning, or gene expression analysis for a client.

Student self-reported learning gains

Comparison of Course-Embedded Research Activities in Bio 460 (Physical Biology of the Cell) and Bio 436 (Molecular Biology Lab)

Results:

• Students were unanimously positive about their CUR experiences in both courses—this was mainly reflected in student comments

• Both CURs generated research products, both written (paper or proposal) and tangible (DNA construct or Molecular movie)

• Both CURs attracted students to the instructor’s research lab to continue working on related projects

• Both CURs produced useful tangible products

• Molecular Biology Lab: DNA constructs directly used in research

• Physical Biology: evidence that UGs can carry out computation, used in a grant proposal, but nothing directly related to research

Figure 1. Student self-reported learning gains (for grouped SLOs) on a scale from 1 to 4: I don’t recognize this topic/idea (1), I recognize the topic/idea, but I would not be able to provide a good response (2), I could comfortably discuss with another student, but am not ready for this on an exam (3), I could confidently respond to this on an exam or discuss with my professor (4). Blue bars represent prior understanding and orange bars represent the change in understanding that resulting from the course.

Conclusions • All students were able to generate high quality molecular models and a few of them were

able to acquire several nanoseconds of MD simulation • Students were extremely excited by results • Students were engaged in work they’ve never experienced, were working on topics that

genuinely interested them, and were able to relate their work to future careers • Resources Needed in Future:

• Highly trained and experienced teaching assistant to carry out highly technical tasks and to manage jobs.

• Laptops for all students

Conclusions:

• Both CUR approaches were valued and positive experiences for everyone involved, but they take slightly more prep time and require a TA

• Molecular Biology Lab produced more useful research products than Physical Biology because projects were client-selected (not student-selected)

Novice Mature Learner

Examples of Course-Embedded Research in Physical Biology of the Cell

C-term

PDZ domains are critical for cell signaling but we don’t know how they recognize their targets Here, Megan found that the end of the PDZ domain becomes ordered when it binds to its target protein, but is disordered in its absence

Student Comment: “I am now much more familiar with the complex ideas and techniques behind the data. I am now more confident in my interpretations and can more easily break down complex ideas into their basic parts.” “VMD simulations were a great way to delve into the biophysical realm of biology.”

Funding 2014 CATL Learning by Design Program 2015 Office of Undergraduate Research and Creativity

β-amyloid is the cause of Alzheimer’s disease, but we don’t know why this peptide spontaneously forms a dangerous fibril—Marissa found that it could be due to oxidation Native β-amyloid is a stable alpha helix, but when it is oxidized, β-amyloid loses its alpha helix structure, which probably leads to fibril formation (plaques)

time (10 nanoseconds)

time (10 nanoseconds) time (10 nanoseconds)