Teaching challenging concepts

to transform learning

Published August 08 2016

Most of us teaching biochemistry and molecular biology at colleges and universities are motivated by love of the discipline and relish the opportunities we have to share our excitement with our students. Yet few of us have received formal training related to teaching, and we may struggle to engage students with the material in deep and meaningful ways.

Recently, the American Society for Biochemistry and Molecular Biology brought communities of faculty together to learn about best practices in teaching and to share expertise. This work, funded by a grant from the National Science Foundation, resulted in the publication of foundational concepts and skills for BMB.

A growing body of research reveals that many students exhibit incomplete or incorrect understanding of essential or “foundational” knowledge in BMB (1, 2, 3). Foundational concepts include such ideas as energy in biological systems, macromolecular structure and function, genomic information storage, and the variety of scientific skills necessary for discovery.

Now that foundational concepts have been defined, an important question arises. Can undergraduate BMB curricula be reimagined to emphasize and clarify those concepts that are most important and most challenging to master? With the help of something called threshold concepts, the answer may just be yes.

Foundational concepts encompass the breadth of a discipline and describe all of the basics that an expert would know. Threshold concepts are those ideas that are most difficult and central to understanding a discipline. Although there is often overlap, identification of threshold concepts allows teachers to tailor instruction to emphasize pivotal concepts with the hope that once students understand threshold concepts deeply, proficiency with other concepts will follow more easily.

In box 1, I’ve described the five threshold concepts of steady state, biochemical pathway dynamics and regulation, the physical basis of interactions, thermodynamics of macromolecular structure formation, and free energy. The chart shows how once students understand a threshold concept, a ripple effect of unlocking other biochemical ideas takes place and connections to additional processes become apparent. If students don’t experience these insights, they may become stuck and be unable to progress as learners.

Threshold concepts also provide a starting point for focused curricular redesign, since an intentional approach to teaching threshold concepts is likely to result in the greatest improvement in student learning (4). In their book “Overcoming Barriers to Student Understanding: Threshold Concepts and Troublesome Knowledge,” Jan Meyer, Ray Land and colleagues suggest that threshold concepts “be viewed as ‘jewels in the curriculum’ insomuch as they provide opportunities for students to gain important conceptual understanding” (5).

Meyer and Land also suggest that threshold concepts can be identified for any discipline and have four defining characteristics (6):

  • Transformative: Once a threshold concept is understood, a student’s perception and comprehension of a subject radically alter. In addition to cognitive development, learning of threshold concepts can alter a student’s self-perception or sense of identity. For example, students may shift from viewing themselves as students of biochemistry to recognizing that they have begun to think like biochemists.
  • Irreversible: Once a threshold concept has been understood deeply, students are unlikely to forget it. The concept becomes central to how students think about everything else in the field. Experts have difficulty remembering how they understood the discipline prior to understanding threshold concepts.
  • Integrative: Threshold concepts bridge concepts within a discipline and among disciplines. Once understood, previously hidden connections within a discipline, and perhaps even across disciplines, are apparent.
  • Troublesome: Most (but not all) threshold concepts are troublesome for students and can be difficult for a number of reasons. However, although threshold concepts tend to be troublesome, not all “troublesome knowledge” has a threshold concept at its source.

We worked with a national community of more than 50 students and 75 faculty members to identify threshold concepts for the field and currently are collaborating with biochemistry colleagues to design instructional and assessment materials targeting these concepts. Reference 7 has a complete description of the concepts and the process used to identify them. Although the goal of our project was to transform student understanding of BMB, faculty have benefitted unexpectedly from transformative experiences as well as their understanding of biochemistry continues to evolve (see “Faculty experiences with threshold concepts”). We continue to expand the community of people engaged in improving learning and teaching in BMB using threshold concepts. If you are interested in joining us, please get in touch!

Box 1

Name Knowledge statement(s) Biochemical ideas that are unlocked once this concept is understood Connections that were invisible prior to deep understanding of the concept
Steady State

• Living organisms constitute open systems, which constantly exchange matter and energy with their surroundings, yet net concentrations remain relatively constant over time. This dynamic, yet outwardly stable condition is referred to as a steady state.

• “Steady” is not synonymous with chemically “stable.” Concentrations are determined by kinetic, rather than thermodynamic factors. Hence, biological systems do not exist in a state of chemical equilibrium.

• If an organism reaches chemical equilibrium, its life ceases. Consequently, organisms have evolved extensive regulatory systems for maintaining steady state conditions.

• Steady state is an emergent process that results from regulation of numerous biological reactions.

• Steady state is a metastable condition that can be maintained only because of constant input of energy from the environment.

• Steady state defines the conditions of life under which chemical reactions take place in cells and organisms. Therefore an understanding of steady state is necessary in order to correctly contextualize all of biochemistry.

• Once the condition of steady state is recognized, the purpose of complex regulatory systems in maintaining steady state and their connections to each other become apparent.

• Once the metastable nature of steady state is recognized, the importance of multi-tiered energy storage systems (starch, glycogen, triglycerides, etc) becomes apparent.

Biochemical pathway dynamics and regulation

• Reactions and interactions in biological systems are dynamic and reversible.

• Directionality of processes depends on the free energy and relative concentrations of reactants and products available.

• Observable flux is the net result of forward and reverse processes.

• Enzymes control rates of forward and reverse reactions.

• Enzyme activity is highly regulated.

• Chemical drivers result in bulk (emergent) properties observed in biological systems.

• Enzyme-mediated regulatory mechanisms allow pathways to be sensitive and responsive to the needs of the organism.

• Enzymes act as gatekeepers rather than drivers of chemical change.

• Once these concepts are understood, predictions can be made about 1) how biochemical pathways are likely to respond to changes environmental conditions and 2) cause and effect of fluctuations in biochemical pathways.

Name Knowledge statement(s) Biochemical ideas that are unlocked once this concept is understood Connections that were invisible prior to deep understanding of the concept
The physical basis of interactions

• Interactions occur because of the electrostatic properties of molecules. These properties can involve full, partial, and/or momentary charges.

• Once this concept is understood, similarities between different types of interactions become clear. Although interactions are given different names, they are all based on the same electrostatic principles.

• Once this concept is understood, similarities between different types of interactions become clear. Although interactions are given different names, they are all based on the same electrostatic principles.

Thermodynamics of macromolecular structure formation

• Interactions in biological systems almost always take place in aqueous solution.

•Bulk interactions in an aqueous system have an entropic component.

•Enthalpic and entropic contributions are responsible for biological structure.

• Protein folding, the assembly of lipids into micelles and bilayers, the association of polypeptide subunits to form oligomeric proteins, base pairing of DNA and RNA molecules, and all other biological interactions are driven by a common set of thermodynamic forces.

• The aqueous environment of the cell plays an active and essential role in biochemical structure formation.

• When the entropic and enthalpic forces that drive processes like protein folding and binding are understood, predictions can be made about the conditions under which these events will occur and what effect perturbations, like mutations, will have.

Free Energy

• The tendency towards equilibrium drives biological processes.

• Differences in free energy drive the chemical transformations underlying biological function.

• By providing a direct link between a thermodynamically favorable reaction with a thermodynamically unfavorable one, enzymes enable biological systems to drive a normally unfavorable reaction by coupling it to one with a large and favorable free energy change.

• Enzymes affect reaction rate yet do not affect equilibrium position.

• Biological systems use favorable processes to drive less favorable processes, which allows for maintenance of steady state.

• Once this concept is understood, the relationship among free energy, equilibrium, and steady state becomes apparent.

Faculty experiences with threshold concepts


I describe myself to students as a protein chemist and biophysicist as I evolved from my first undergraduate research project and an initial major in physics over 40 years ago. Both of these backgrounds led to a deepening insecurity as I attempted to help my students understand the hydrophobic effect in protein folding. An unease arose one day when I knew that I had given a student an inadequate explanation for its role in protein structure and stability because I never fully understood it myself. This unease exploded when I attended a two-day workshop at the University of Minnesota on the hydrophobic effect presented by Ken Dill. Driving home after the first day, my understanding of the hydrophobic effect seemed to have collapsed. I questioned whether I ever understood it. On the second day, I became aware that I had achieved a much deeper understanding of this threshold concept. Previously unappreciated and misunderstood differences in plots of heat capacity vs. temperature for protein denaturation suddenly became clear as I internalized a more nuanced understanding of the hydrophobic effect based on characteristic heat capacity changes with changes in local environments of nonpolar groups. Compensatory enthalpic and entropic changes relating to changes in water structure made sense. I relate this story to my students as they struggle with the topic and tell them that we all struggle as we seek to understand our internal and external worlds.

Henry Jakubowski, professor of chemistry, College of Saint Benedict Saint John’s University


The idea of threshold concepts seems very straightforward until you find yourself in a room of experts contemplating the threshold concepts of your discipline. In the midst of a discussion of steady state and why this should be a threshold concept in biochemistry, I realized that I did not truly understand the difference between equilibrium and steady state and therefore had not yet fully crossed that threshold myself. I used the words interchangeably, and because equilibrium was the concept with which I was most familiar, I taught students many aspects of what I now recognize as steady state as equilibrium. At first glance, whether the system is opened or closed seemed like a minor issue, but like a threshold concept should, understanding this difference at a deeper level has changed my understanding of the chemistry of living organisms and why it needs to be addressed differently than chemistry in a test tube. This change in my perception of the concept of steady state and its importance in developing a deep understanding of biochemistry has definitely influenced the way I teach protein-ligand and enzyme-substrate interactions, inhibition, regulation, and metabolic flux.

Tracey Murray, associate professor and chair of chemistry and biochemistry, Capital University


  1. Sears, D.W. et al. Biochem. Mol. Bio. Edu.35, 105 – 118 (2007).
  2. Villafañe, S.M. et al. Chem Educ. Res. Pract.12, 210 – 218 (2011).
  3. Linenberger, K.J., & Bretz, S.L, Biochem. Mol. Bio. Edu.43, 213 – 222 (2015).
  4. Entwistle, N. Threshold concepts and transformative ways of thinking within research into higher education in “Threshold concepts within the disciplines” Land, R.; Meyer, J.H.F., and Smith, J., eds., Sense Publishers, Rotterdam, 21 – 35 (2008).
  5. Land, R. et al. Conclusions: implications of threshold concepts for course design and evaluation in “Overcoming barriers to student understanding: threshold concepts and troublesome knowledge” Meyer J.H.F. & Land, R., eds.; Routledge, London, 195 – 206 (2006).
  6. Meyer, J.H.F. & Land, R. Threshold concepts and troublesome knowledge. In Improving student learning — ten years on Rust, C., ed. Oxford, 412 – 424 (2003).
  7. Loertscher, J.L. et al. CBE Life Sci. Educ. 13, 518 – 528 (2014).
Jennifer Loertscher Jennifer Loertscher is a professor of chemistry at Seattle University.