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Justine Paul

Justine Paul lab photo




Syracuse University


Bretton Fletcher
Christine Tchounwou

Faculty Sponsor(s): 

Cyrus Safinya

Faculty Sponsor's Department(s): 


Project Title: 

Determining the Electrostatic Interactions of Microtubules and Chemically Altered Tau

Project Description: 

Microtubules (MTs) are highly negatively charged protein nanotubes assembled from α-/β-tubulin heterodimers and play several vital roles in cytoskeletal stability and chromosome organization during cell division. Microtubule associated proteins (MAPs) help regulate dynamic instability, the active polymerization and depolymerization of MTs. MAP-tau is a positively charged, intrinsically disordered protein that binds to the MT wall to promote and stabilize MT polymerization.

The charged state of tau is highly regulated by post-translational modifications such as phosphorylation. Misregulation of these modifications has been implicated in a range of neurodegenerative diseases such as Alzheimer’s. The Safinya group is working to understand how the electrostatic interactions affect the structure of these biological nanoscale assemblies. The current aim is to understand the interactions of pseudo-phosphorylated tau, on in vitro MT assembly structure. This summer, we have been working towards purifying several point mutated pseudo-phosphorylated tau isoforms using Ni2+ column chromatography. We first transform competent E.coli cells with our protein plasmid of interest, culture, and lyse the bacteria. Lastly, we purify the tau protein through various column chromatography techniques. Once purification of tau is successful, synchrotron small angle x-ray scattering (SAXS) techniques will provide the ability to collect information regarding the structure of these assemblies. From this, we can measure inter-microtubule forces to understand the behavior of the tau projection domains. This research will allow us to gain insight on the electrostatic interactions between MTs and tau which may lead to future hypotheses about the biochemical behavior of neurodegenerative diseases.