Biophysics and Physiological Modeling

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There is a growing movement within biology to transform the undergraduate curriculum. Major goals are to develop active-learning teaching materials based on educational research, and to engage students in discovery-based activities so that they perceive biology as an evidence-based science with testable hypotheses that are supported by experimental data. As part of a National Science Foundation (NSF) grant, I'm developing a series of modules that engage students in inquiry-based activities to introduce them to the process of scientific modeling and validation. The modules are a self-contained series of interactive self-study guides for undergraduates (both with and without calculus). The modules are designed so that students can complete them without additional assistance, making them suitable for use as stand-alone homework exercises or computer labs, or for a complete discovery-based active-learning course.

These modules are aimed at biology, pre-med and physical science majors interested in learning about physiological systems and processes. Module 1 introduces the marble game and provides a gentle introduction to quantitative modeling using Excel. This marble game provides a realistic conceptual framework for understanding a wide range of molecular transport processes in physiology. These transport phenomena are so fundamental to physiology that "Transport Processes" was ranked as the second most important topic in pre-medical education (after "Nucleic Acids") in a 2011 survey conducted by the Association of American Medical Colleges (AAMC). Modules 1 and 2 have been peer reviewed by the Archive Board of the American Physiological Society (APS). Module 1 was selected to be one of four resources featured on the front page of their NSF-funded online portal: "The APS Archive of Teaching Resources" in November 2011 and Module 2 was a featured "Inquiry-Based K-12 Science" resource in March and April 2012. If you’re interested in trying out Module 1, check out the APSArchive listing, the Modules homepage or go straight to Module 1.

In later modules, we’ll use the marble game to develop simple models that can be implemented in an Excel spreadsheet to discover more about these transport process. Using the spreadsheet, we’ll discover what the practical implications of the model are, and then we’ll compare the model predictions with experimental data (if available). For example, in the early modules, we’ll develop a simple (pharmacokinetic) model of how drugs such as acetaminophen (paracetamol) and penicillin are eliminated from the body. While this model (and the other models we’ll develop) are particularly simple (and are therefore easy to understand), the molecular modeling approach is actually a cutting-edge research technique! - a kinetic Monte Carlo simulation.

Once we’ve developed the drug elimination model, we’ll compare it's predictions with published data for elimination of piperacillin (a form of penecillin) by healthy volunteers and intensive care patients on heart-lung machines. As we'll discover the marble game model does a fantastic job of predicting what will happen in the healthy volunteers... There are numerous other topics that we can investigate with a similar approach including:

distribution of oxygen, carbon dioxide and glucose osmosis and homeostasis of erythrocytes fluid dynamics and blood flow kinetics of motors, carriers, and RNA

membrane transport and drug delivery diffusion of neurotransmitters ion channel permeation and gating ion channels and the action potential

I’m currently working on developing new topics and approaches. If there is a topic that you’re interested in, that you think might be fun to do, please let me know.

Beta testing and evaluation

Module 1 has now been peer-reviewed by the Archive Board of the American Physiological Society (APS). If you’re interested in trying out Module 1, check out the APSArchive listing, the Modules homepage or go straight to Module 1.

Addtional modules are also available. If you’re interested in evaluating them, please email me. I'm also looking for collaborators who are interested in evaluating these materials as an example of how science education projects evolve and how to determine student learning benefits from curricular changes. If you are interested in collaborating on a Research Coordination Networks - Targeted Undergraduate Biology Education track (RCN-UBE) proposal, please let me know.

Self-study guides

The modules are self-contained workbooks. Hence, you (or your teaching assistant (TA)) can use them as supplemental homework assignments or computer labs, or for an entire discovery-based active-learning course.

Prerequisites and level

The modules assume high school chemistry, and (algebra-based) physics. No calculus required! However, optional sections are included for those students with calculus. They are also suitable as an introduction to scientific modeling and validation for students who didn’t take a formal course in biophysics, e.g. graduate or medical students in interdisciplinary Biophysics or Molecular Biology PhD programs or MD/PhD programs.

Notwithstanding that the materials are accessible to well-prepared high school students; they also contain materials that have traditionally been taught at the graduate level. As an example, the kMC simulation technique (or the chemical master equation) is not in the traditional undergraduate curriculum even for chemistry or physics majors. The primary focus of the modules is quantitative scientific modeling with physiology applications.

Background

BIO 2010 - Transforming Undergraduate Education for Future Research Biologists (National Academies Press 2003) motivated me to write the NSF CCLI (now TUES) proposal for this project. The modules also address many of the core competencies identified in the report of the AAMC-HHMI Committee: Scientific Foundations for Future Physicians published by the Association of American Medical Colleges (AAMC) 2009 and they address many of the issues discussed by the "Overarching and unifying key concepts and competencies - Group B - Quantitative Competency" working group at the AAAS conference: Transforming Undergraduate Biology Education: Mobilizing the Community for Change (July 15-19, 2009) sponsored by the NSF. My presentation at this conference was about this Biophysics and Physiological Modeling project. The revised Vision and Change Final Report is now available as are the Ratings of the Importance of Natural Sciences, Research Methods, and Statistics Topics on the MR5 Content Surveys, 5th Comprehensive Review of the Medical College Admission Test® (MCAT), MR5 Preliminary Recommendations, Creating Scientifically Lieterate Physicians, MR5 Science Content Survey of Undergraduate Institutions, Preview Guide for MCAT 2015 and MCAT website.

Student researchers/testers

I would like to thank my students in Biol/Chem/Phys 323 - "Biophysics" and Biol 310 - "Physiological Modeling", for their patience, support, encouragement and enthusiasm. I couldn’t have done it without you!

I would also like to thank the following students for their assistance: Nathan Kucera, Jonathan Rink, Ashley Rink, Stephanie Denny, David Faber, Matthew Harrison, James Norris, Muzamil Arshad, Amar Khatri, Luke Cox, Rama Wahood, Tricia Avanzado, Joy Holowicki, Madhish Patel, Jacob Polaski, Sabrina Sanchez, Alexis Wadowski,

Mohammad Arfeen, Kristine Baldwin, Joseph Esner, Branko Milicevic, Daniela Janevska, David Kamber, Robert Kasper, André Molina, Garrick Moll, Ankit Parikh, Jonathan Pollock, John Romal, Sawyer Masonjones, Edyta Frankiewicz, Katie Maezes, Justin Villanueva, Tiffany Warzecha, Nicole Worthem, Thymur Chaudry, Owais Hameed, Robert Horsley, Joey Hua, Tahreem Iqbal, Bohdan Khomtchouk, Raquel Tobar Rubin, Megan Wisniewski, Dima Saigh, Amanda Stachowicz, Lina Savickas, Jared St. John, Diyanka Patel and Le-Ander Gibbs.

Peer-reviewed publications

• P. H. Nelson Biophysics and Physiological Modeling: Model Validation and Penicillin. (2010) MedEdPORTAL: https://www.mededportal.org/publication/8081
  (part of the uScience Inaugural Collection)
• P. H. Nelson A permeation theory for single-file ion channels: One- and two-step models (2011) J. Chem. Phys. 134, 165102*
  (a Module on ion channel permeation is in preparation)
• P. H. Nelson Teaching Physiology with the Marble Game (2011) APSArchive.org http://www.apsarchive.org/resource.cfm?submissionID=4999
  (Featured resource in November 2011)
  (Featured Inquiry-Based K-12 Science resource in March and April 2012)
• P. H. Nelson Teaching Physiology with the Marble Game 2: Algorithms and TYLENOL® (2012) APSArchive.org http://www.apsarchive.org/resource.cfm?submissionID=6152

Presentations

• P. H. Nelson (2011). Connecting ion channel simulations to experiment APS March Meeting 2011 56(1)
• P. H. Nelson (2011). Teaching Physiology with the Marble Game FASEB J. 25, 481.5
• S. I. Sanchez, A. Wadowski and P. H. Nelson (2011). Developing and testing a quantitative model of ion permeation based on the MacKinnon mechanism FASEB J. 25, 1042.24
• A. Wadowski, S. I. Sanchez and P. H. Nelson (2011). A mathematical equivalence between the MacKinnon model and the association/dissociation model explains its apparent success in explaining ion channel permeation FASEB J. 25, 1042.25
• P. H. Nelson (2012). Teaching Biophysics with the Marble Game Biophysical Society 56th Annual Meeting 2012 Pos-L333
• P. H. Nelson (2012). A new pedagogy for ion channels: they’re permeases, not pores! FASEB J. 26, 719.9

Funding and awards

Six Star Science Teacher-Recommended Collection: Cellular Transport
NSF Grant DUE-0836833
AAAS Conference: Transforming Undergraduate Biology Abstracts
AAMC MedEdPORTAL for Undergraduate Science (uScience)
HHMI Grant 52002669
Title III Grant - Benedictine University
NIH Post-Doctoral Fellowship in Quantitative Biology GM20584

Searching, resources and portals

NSDL, ben (BiosciEdNet), www.apsarchive.org, CSERD, the Gateway, comPADRE, www.the-aps.org, Disseminating CCLI Educational Innovations, SALG, URSSA, Mobilizing STEM Education for a Sustainable Future, ESTEEM, PER User's Guide, DiscoverEd, Open Courseware, HHMI's BioInteractive, Biophysical Mechanisms (Biophysics Textbook Online - Biophysical Society), HHMI Membrane Awakening, BPM Hotlist

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Provided by Circle4.com
This material is based upon work supported by the National Science Foundation under Grant No. 0836833.
Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

This page was last updated on April 9, 2013 by pHn.
© Peter Hugo Nelson 2009-13
All Rights Reserved

If you use these materials, please cite the project as a whole as:
        Nelson, P. H. (2013) Biophysics and Physiological Modeling; Available from: http://circle4.com/biophysics/
Please cite an individual module (e.g. Module 1) as:
        Nelson, P. H. (2013) Biophysics and Physiological Modeling - Module 1: Introduction - marble game (v.3.0); Available from: http://circle4.com/biophysics/

Copyright Information:

* This article appeared in J. Chem. Phys. and may be found at (P. H. Nelson J. Chem. Phys. 134, 165102 (2011)). Copyright American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics.