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Jehan Keval

Jehan Keval,


Cell and Developmental Biology


University of California, Santa Barbara


Christine Tchounwou
Bretton Fletcher

Faculty Sponsor(s): 

Cyrus Safinya

Faculty Sponsor's Department(s): 

Cellular, Molecular and Developmental Biology

Project Title: 

Mimicking Neurodegenerative Modifications to Microtubule Associated Protein Tau in vitro

Project Description: 

Microtubules (MTs) are cytoskeletal proteins that provide structure to neuronal axons in part by the microtubule associated protein (MAP) tau, which is known to bind and stabilize MTs. Tau has four binding domains that interact with the MT surface through possible electrostatic interactions to promote MT stabilization. While the exact mechanism of how tau interacts with MTs remains unknown, the disruption of these interactions is thought to cause neurodegenerative symptoms. One well characterized observation of dysfunctional tau in neurodegenerative diseases is the formation of neurofibrillary tangles (NFTs) in neurons due to toxic self-interactions of tau. The exact pathway of NFT formation is unknown, but it is suspected that misregulation of post-translational modifications such as phosphorylation may play a role in hindering tau’s binding affinity. By inducing pseudo-phosphorylation at specific sites in and around the MT binding domain, I will determine if tau phosphorylation is indeed interfering with its binding ability and leading to NFT formation. In order to understand the role of phosphorylation, we have purified recombinant site-directed mutagenic tau by exploiting tau’s innate biochemical characteristics. By utilizing our mutant constructs, we can perform MT polymerization and stability experiments using small angle x-ray scattering (SAXS) and transmission microscopy (TEM). Results from these in vitro experiments will allow us to understand the unique biochemical interactions between tau and MTs and how perturbing these interactions can lead to the hallmarks of neurodegenerative diseases.