CONNECTING PROTEIN STRUCTURE AND FUNCTION FROM CLASSROOM TO CHROMATIN: EDUCATIONAL INSIGHTS AND SPN1-DEPENDENT REGULATION OF QUIESCENCE AND CELLULAR AGING

Abstract

Understanding how structure gives rise to function is a unifying principle in both biology and biochemistry. Yet this relationship presents challenges across multiple scales, from student learning in the classroom to chromatin regulation in living cells. This dissertation bridges educational research and molecular biology to examine how structure–function relationships are constructed, interpreted, and regulated. It connects cognition to chromatin.At the instructional level, this work examined how undergraduate students construct and revise their understanding of protein structure and function. Although “structure determines function” is a foundational concept in biochemistry, students frequently struggle to visualize proteins as dynamic three-dimensional molecules and to connect structural features to biological roles. Through qualitative analysis of survey responses collected across a semester long non majors biochemistry course, existing classifications of protein misconceptions were expanded, and three newly characterized categories were identified: misconceptions about protein stability based on orientation, misconceptions about inherent protein dynamics, and misconceptions about the relationship between structure and function. These misconceptions were strongly associated with challenges in visuospatial reasoning. Despite active learning interventions, most students demonstrated limited conceptual progression over time. At the molecular level, cellular quiescence is a conserved survival strategy that supports longevity. However, how distinct quiescent states influence lifespan remains incompletely understood. Using Saccharomyces cerevisiae as a model system, this study investigated the coordinated phenotypes associated with expression of the Spn1141-305 mutant. Expression of Spn1141-305 was associated with extended chronological lifespan relative to full length Spn1, indicating a longevity phenotype during quiescence. In addition to increased lifespan, Spn1141-305 cells exhibited a distinct quiescent chromatin architecture. Approximately thirty percent formed incompletely separated mother–daughter assemblies that were observed exclusively in quiescent Spn1141-305 populations. Functional analysis further revealed enhanced exit from quiescence in Spn1141-305 cells compared to wild type.Together, these findings suggest that Spn1141-305 defines a distinct and reversible quiescent state. Structure shapes survival. Across both domains of inquiry, structure–function reasoning emerges as both a molecular mechanism and a cognitive challenge. By integrating insights from science education research with mechanistic studies of chromatin regulation, this dissertation underscores the central role of structural reasoning in advancing scientific discovery and scientific learning.