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The Pielak Group

My students and I use the formalisms of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand the structure, stability, and function of globular and intrinsically-disordered proteins in physiologically relevant environments.

Gary Pielak wins Fulbright Award

Gary Pielak has received a Distinguished Scholar Fellowship from the Fulbright U.S. Scholar Program, supporting a four-month research residency at the Hebrew University of Jerusalem.

For decades, macromolecular crowding theory held that the dense interior of the cell stabilizes proteins by favoring compact, folded states – the crowded-elevator analogy. Testing that assumption, the Pielak lab found the opposite was often true: when proteins rather than sugars serve as crowders, and in living cells, proteins frequently become less stable. The dominant effects come not from excluded volume but from chemical interactions between a protein and its surroundings.

Working with longtime collaborator Daniel Harries, the lab built a new model combining both contributions – steric squeezing and transient chemical interactions – using a single adjustable parameter. Though not derived from polymer scaling laws, it reproduces them, suggesting it captures something fundamental about crowded systems. AI-designed protein families now allow the model to be tested under biologically realistic conditions.

Read the full article at UNC Chemistry