$1.2M Keck Foundation Award Supports IBBR Research on Shape-Shifting Proteins

IBBR is proud to congratulate Dr. John Orban’s lab, along with collaborators from UC-Merced and Caltech, on receiving a $1.2 million research award from the W.M. Keck Foundation. This prestigious grant will propel an ongoing project exploring metamorphic proteins; proteins that can adopt more than one folded state.

Unlike endotherms that have internal mechanisms of controlling their own temperature, ectotherms, such as bacteria, do not, and rather experience temperature from the environment directly. This project explores the hypothesis that it is metamorphic proteins that play a critical role in aiding bacteria to sense, adapt to, and survive in fluctuating thermal conditions.

In “Unveiling the cold reality of metamorphic proteins,” published in PNAS last year, Drs. Orban and LiWang have analyzed 26 known metamorphic protein pairs. This revealed a consistent pattern that suggests metamorphic proteins may regulate function by shifting the balance between more ordered and less-ordered states, with temperature as an underlying trigger for the change in states. With this grant, the funded project will aim to expand upon this work through further experimental investigation to characterize a greater range of temperature-dependent metamorphic proteins.

By identifying and characterizing new metamorphic proteins, their work also challenges the long-standing dogma in biology that one amino acid sequence only codes for one structure which contributes to only one function. The findings from their study may also carry broad implications for bacterial resilience, pathogenesis, and possibly even agriculture.