Understanding Clock Gene Regulation by Constructing a Qualitative Representation

We developed a lesson where students construct a qualitative representation to learn how clock genes are regulated. Qualitative representations provide a non-numerical description of system behavior, focusing on causal relation-ships and system states. They align with human reasoning about system dy-namics and serve as valuable learning tools for understanding both domain-specific systems and developing broader systems thinking skills.
The lesson, designed for upper secondary and higher education, is imple-mented in the DynaLearn software at Level 4, where students can model feedback loops. Students construct the representation step by step, guided by a structured workbook and built-in support functions within the software. At each step, they run simulations to examine system behavior and reflect on the results through workbook questions. To ensure scientific accuracy, the representation and workbook were evaluated by domain experts.
The lesson begins with modeling how increasing BMAL:CLOCK activity enhances the transcription of PER and CRY genes through binding to the E-box. Next, students explore how mRNA production and degradation—two opposing processes—regulate mRNA levels. This is followed by modeling translation at the ribosomes, where PER and CRY proteins are synthesized and subsequently degraded, again illustrating competing regulatory process-es. Students then model how PER and CRY proteins form a complex that translocates to the nucleus, inhibiting CLOCK:BMAL binding and establish-ing a negative feedback loop. Finally, they extend their understanding by ex-ploring how CLOCK:BMAL also regulates the AVP gene, linking clock genes to broader physiological processes.