NSF Postdoctoral Fellowship in Biology FY 2013

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Order within disorder: Understanding the conformational landscape of intrinsically disordered proteins Proteins bind specific partners to perform functions such as building molecular structures and transmitting molecular signals. Traditionally, proteins were understood to have a stable structure, however, research in the last twenty years has revealed that over one third of eukaryotic proteins contain long unstructured regions. Such intrinsically disordered proteins transition among an ensemble of conformations, a behavior responsible for their ability to bind multiple partners, and leading to their enrichment in cellular pathways. In certain classes of bacterial antitoxin proteins, transitions between extended and compact conformations directly control stress response pathways. Using a hybrid computational and experimental approach, the PI will determine the (1) conformational ensemble of a specific antitoxin, (2) function of each conformation, and (3) transition rates between the conformations. Mutations that modify the antitoxin?s conformational ensemble affect interaction with other macromolecules in the toxin-antitoxin regulatory network will be investigated.This project will provide new understanding of stress response pathways in bacteria and will yield novel methods for determining transient conformations of intrinsically disordered proteins and their functions. The PI will obtain training in experimental methods and expand her computational abilities. Algorithms and results of this work will be placed on the web to facilitate and advance future research in the field. Additionally, the PI will mentor a summer high school student on a bioinformatics project examining disordered regions of antitoxin proteins.