Diane H. Munzenmaier, PhD
Program Director
Milwaukee School of Engineering

For most of my career, I taught physiology and genetics to medical students and graduate students.  My experiences with many students who had difficulty succeeding in these courses led me to the realization that the way high school and college students learn the biological sciences does not translate to effective physiology learning and understanding at the graduate level.

Medical students, by virtue of their admission to medical school, have, by definition, been successful academically prior to matriculation and have scored well on standardized exams.  They are among the best and brightest that our education system has to offer.  Yet, I have always been amazed at how many medical students truly struggle with physiology.  It is considered by many students to be the most difficult discipline of the basic medical sciences.  Most students come into medical school as expert memorizers but few have the capacity or motivation to learn a discipline that requires integration, pattern recognition, and understanding of complex mechanisms.  My overall conclusion is that high school and college level biological science education does not prepare students to succeed in learning physiology at the graduate level.  Furthermore, I believe if students were prepared to better appreciate and excel in basic physiology at earlier grade levels, the pipeline for graduate education in the physiological sciences would be significantly increased.

Over the past 5 years, it has become a passion of mine to promote a new way of teaching biology and physiology: one that helps students make connections and that lays a conceptual framework that can be enhanced and enriched throughout their educational careers, rather than one that promotes memorization of random facts that are never connected nor retained.  I recently joined the Center for Biomolecular Modeling at the Milwaukee School of Engineering (MSOE CBM) in order to focus on developing materials and activities to promote that type of learning and to provide professional development for K-16 teachers to help them incorporate this type of learning into their classrooms.

One of my first projects was to develop resources to allow students to study the structure-function relationships of a specific protein important in physiology and use that understanding to relate it to relevant physiology/pathophysiology concepts.  The program is called “Modeling A Protein Story” (MAPS) and, so far, I have developed resources for 3 different project themes: aquaporins, globins, and insulin.

The overall concept is for the students to build their understanding slowly and incrementally over time, usually as part of an extracurricular club.  They start by understanding water and its unique properties.  Then they learn about proteins and how they are synthesized and fold into specific 3D conformations in an aqueous environment based largely on their constituent amino acids and how they interact with water.  Eventually they progress to learning about the unique structure of their protein of interest and how it is related to its function.  Once they have developed a solid understanding of that protein, they work in teams to choose a specific protein story that they will develop and model.  This includes finding a structure in the Protein Data Bank, reading the associated research paper to determine what was learned from the structure, designing a model of the structure in Jmol, an online 3D visualization software, and 3D printing a physical model of the protein that helps them tell their story.  Stories can be anything related to the theme that the students find in their research and consider interesting.  For example, student-developed aquaporin stories have ranged from AQP2 in the kidney to AQP4 in the brain to the use of AQP proteins to develop biomimetic membranes for water purification in developing countries.  By choosing projects that students are interested in, they more readily accept the challenge of reading primary research literature and trying to piece together a confusing puzzle into an understandable “story”. 

In the past year, I have used the insulin theme resources and piloted an active learning project-based curriculum at the undergraduate, high school, and middle school levels on insulin structure-function, glucose homeostasis, and diabetes mellitus.  The type of learning environment in which this curriculum was introduced has varied.  Middle school level children participated in the active learning environment as part of a 2-week summer camp.  High school students from an innovative charter school in downtown Milwaukee were introduced to the project-based curriculum as a 9-week seminar course, and the activity was taught to freshman biomolecular engineering students at the Milwaukee School of Engineering as a team project in their first quarter introductory course.

Some of the activities utilized materials that we have developed at the MSOE CBM and were subsequently produced for distribution by our sister company, 3D Molecular Designs.  Others utilize resources that are readily available online such as those available at the Protein Data Bank at their educational site, PDB-101.  Finally, still other resources have been developed by us specifically for this curriculum in order to help the students move between foundational concepts in an attempt to help them make important connections and to assist them in developing their conceptual framework. 

One of the activities that helps them try to make sense of the connection between glucose and insulin is this “cellular landscape” painting by Dr. David Goodsell at Scripps Research Institute and available at PDB-101.

They learn the basic concept that when blood glucose increases after a meal, insulin is released from the pancreas and allows glucose to be taken up and stored by the cells.  But how?  When they are given this landscape and minimal instructions, they must look closely, connect it to what they already know and try to make sense of it.  They work together in a small group and are encouraged to ask questions.  Is this a cell?  If so, where is the plasma membrane and the extracellular/intracellular spaces?  What types of shapes do they see in those spaces?  What is in the membrane?  What are those white dots?  Why is one dot in one of the shapes in the membrane?  Why are there yellow blobs on the outside of the cell but not on the inside?  Eventually they piece together the puzzle of insulin binding to its receptor, leading to trafficking of vesicles contain glucose transporter proteins to the plasma membrane, thereby allowing the influx of glucose into the cell.  By struggling to make detailed observations and connections, a story has been constructed by the students as a logical mechanism they can visualize which is retained much more effectively than if it had been merely memorized.

In other activities they learn how insulin in synthesized, processed, folded, stored, and released by the pancreatic beta cells in response to elevated blood glucose.  They use a kit developed by MSOE CBM that helps them model the process using plastic “toobers” to develop an understanding of how insulin structure is related to its function in regards to the shape and flexibility required for receptor binding but also related to its compact storage in the pancreas as hexamers and the importance of disulfide bonds in stabilizing monomers during secretion and circulation in the blood.  

As the students build their understanding and progress to developing their own “story”, the depth of that story depends on grade level and the amount of time devoted to the project.  Undergraduate students and high school students who have weeks and months to research and develop their story tend to gravitate to current research into protein engineering of insulin analogs that are either rapid-acting or slow-release, developed as type 1 and type 2 diabetes medications, respectively.  The basic concepts behind most of these analogs are based on the structure-function relationships of hexamer formation.  Rapid-acting medications usually include amino acid modifications that disrupt dimer and hexamer formation.  Slow-release medications tend to promote hexamer stability.  Middle school students or high school students with limited time to spend on the project may only focus on the basic properties of insulin itself.  The curriculum is driven by the students, so it is extremely flexible based on their capabilities, time, and motivation.  Students ultimately use their understanding of insulin structure-function to design and 3D-print a physical model that they highlight to show relevant amino acid modifications and other details that will help them to present the story they have developed based on their learning progression and research. 

In conclusion, we have found that this type of open-ended project-based active learning increases learning, retention, and motivation at every educational level  with which we have worked.  Students are initially frustrated in the process because they are not given “the answer” but they eventually learn to be more present, make observations, ask questions, and make connections.  Our hope is that introduction of this type of inquiry-based instruction in K-16 biological sciences education will eventually make the transition to graduate level physiology learning more successful.

Diane Munzenmaier received her PhD in Physiology studying the role of the renin-angiotensin system on skeletal muscle angiogenesis. This was followed by postdoctoral study of the role of astrocytes in stroke-induced cerebral angiogenesis. She joined the faculty of the Department of Physiology at the Medical College of Wisconsin in 1999 and the Human and Molecular Genetics Center in 2008. As Director of Education in the HMGC, Dr. Munzenmaier lectured and developed curriculum for medical and graduate school physiology and genetics courses. She developed an ACGME-accredited medical residency curriculum and Continuing Medical Education (CME) courses for physician education. She also enjoyed performing educational outreach to K-12 classrooms and the lay public. She is passionate about education and career mentoring for students of all levels. Her specific interests in biomedical science education are finding engaging ways to help clarify the link between structure and (dys)function in health and disease.