Tim Keller wins Best Student Poster Award at the 57th Rocky Mountain Conference on Magnetic Resonance

Han Lab graduate student Timothy Keller won the Best Student Poster Award at the 57th Rocky Mountain Conference on Magnetic Resonance.

His abstract, titled ESEEM Study of the Initial Stages of Protein Aggregation, reads as follows:

The aggregation of the microtubule stabilizing protein tau has been identified as an important constituent in the formation of amyloid plaques characteristic of neurodegenerative diseases such as Alzheimer’s disease. Monomeric tau protein is an intrinsically disordered protein, which has a propensity to aggregate at three (or four depending on isoform) microtubule binding regions eventually forming beta-sheet strands. While the characteristics/structure of tau protein before and after aggregation has been characterized by a number of methods, the transient intermediate states have been far more difficult to study. In particular, we are interested in whether the hydration water is restructured or relinquished before or during oligomer formation, and whether this is correlated with the microtubule binding regions of tau protein. We have used pulsed EPR to characterize the initial stages of tau protein aggregation; including TM relaxation measurements to monitor oligomer formation and ESEEM to characterize the hydration water upon aggregation of tau protein. We find that immediately after inducing aggregation, we observe a dramatic decrease in TM which is caused by the association of tau protein into oligomers. These oligomers are not yet beta-sheet strands, but the decrease in TM is an indication that tau protein has associated from a monomeric state into dimers or higher order oligomers. In addition, we find that the water accessibility is decreased immediately upon inducing aggregation, however, only at sites which are adjacent to microtubule binding regions. This result indicates that the association of tau protein into oligomers is driven by interactions at the microtubule binding regions.