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Matthew Flagg

Research

In biochemistry classes, students connect thermodynamics and chemistry to macromolecular structures and metabolic pathways. Ideally, students build a coherent mental model of the cell that spans from atoms to proteins, from individual protein-ligand interactions to macromolecular populations that respond to and alter their environment over time. Students use basic principles to explain and predict biological functions.

But to do so, they have to use mathematical, chemical, and spatial reasoning. For many, one or more of those approaches is a cause for anxiety, especially when paired with the idea that biochemistry is a “weeder” class. My biology education research aims to address that anxiety and to ensure that real-world relevance and a sense of awe are emphasized in the classroom, too.

In the lab, my research focuses on “minimally misfolded” proteins. In instances of minimal misfolding, an individual amino-acid substitution causes a protein to be degraded by the ubiquitin-proteasome system, but it does not ablate the protein’s function. It’s been hypothesized that minimal misfolding underlies a broad swath of monogenic human diseases. More generally, protein misfolding is a biomedically critical but poorly understood phenomenon.

We use predictive frameworks and forward genetic screening to identify and characterize minimally misfolded variants of simple proteins. Students gain the practical skills necessary to succeed in the lab, and they formulate and test their own hypotheses, building a durable science identity and intellectual confidence.

Select Publications

  • Flagg, M. P., Lam, B., Lam, D. K., Le, T. M., Kao, A., Slaiwa, Y. I., & Hampton, R. Y. (2023). Exploring the "misfolding problem" by systematic discovery and analysis of functional-but-degraded proteins. Molecular biology of the cell, 34(13), ar125. https://doi.org/10.1091/mbc.E23-06-0248

Biography

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