Conformation of Tau Protein in Polyphosphate Solution

Students

2018
College

Faculty

Professor of Chemistry

Project Summary

Over the past summer, I conducted biochemistry research in the Rhoades laboratory at the University of Pennsylvania. My research experience was made possible due to generous assistance from the Center for Undergraduate Research and Fellowships (CURF) and the Roy and Diana Vagelos Program in the Molecular Life Sciences (MLS).

In the Rhoades lab this summer, I researched the neuronal protein tau. In many neurodegenerative diseases, tau protein forms aggregated tangles, although the conformation of tau’s initial aggregation-prone state is currently unknown. In addition, to study intrinsically disordered proteins like tau, it is difficult to use common methods of determining structure, such as NMR or X-ray crystallography. Therefore, in order to learn more about tau’s aggregation-prone structure, I used a technique this summer called Förster resonance energy transfer (FRET). By attaching fluorescent probes to tau and monitoring the energy transfer between them, this technique allowed me to study how the distances between regions of tau change in the presence of aggregation inducers. As a result, at the end of the summer, I have been able to construct a preliminary model of tau’s conformation in an aggregation prone state, which I am able to compare and contrast with previous models for tau aggregation. Models of tau aggregation, such as this one, are an important first step to understanding how neurodegenerative disease states initially arise.

Personally, this research experience taught me many biochemical techniques, ranging from how purify a protein to how to align a laser pathway. I also got the opportunity, outside of my classwork, to think deeply about how proteins behave in different environments and what factors influence the nuances of proteins’ conformational changes. Finally, having the support from CURF and MLS to work in this lab over the summer has been critical for me to gather data for my chemistry master’s thesis; even more, the experience has confirmed my aspirations to apply for a PhD in biochemistry and continue to do biochemical research with applications in neuroscience.

Conformation of Tau Protein in Polyphosphate Solution