March 11, 2015

Braulio Fernandez

Braulio FernandezMajor and Classification

    Neuroscience

Faculty Mentor

    Xiaojiang Chen, Ph.D., Department of Chemistry

Department

    Dornsife: Neuroscience

Research Gateway Project

    Determining the Crystal Structure of Phosphotyrosine Interaction Domain Containing 1 via Truncations Valued from Comparative Analysis of Homologous Structures

Abstract
Glioblastomas and medulloblastomas are two of the most malignant brain tumors in adults and children, respectively. The Phosphotyrosine Interaction Domain Containing 1 (PID1) protein has emerged in the past couple of years as a potential candidate for novel forms of treatment. PID1 has been linked to providing an inhibitory function in pediatric and adult brain tumors. It has been found that PID1 expression in medulloblastoma and glioblastoma cell lines inhibit colony formation by 68% compared to when it’s absent, thus explaining the higher PID1 mRNA levels found in healthy, recovering brain tumor patients than those in poor health. Additionally, the presence of higher PID1 levels in the brain was found to be correlated to more successful chemotherapy treatments after surgery. The biological mechanism of PID1’s activity is still unknown and thus limits the application of PID1 for possible treatment. Finding the PID1 crystal structure via x-ray crystallography can give insight into its molecular function. PID1 is not conducive to forming a lattice structure so genetic truncations must be made in an effort to promote crystal formation. The modifications made are a product of the alignment between the PID1 genome and a similarly structured protein genome with a solved crystal structure.