Presentation Title

In Pursuit of Phase Separation

Abstract

According to Anfinsen’s structure-function postulate, the ability of linear chains of amino acids to fold into a 3-D structure governs protein’s function. Therefore, the subsequent recognition of intrinsically disordered proteins (IDPs) that fail to form a stable conformation, but yet preserve its biological function, became a “mysterious” phenomenon in protein science. Disorder-based functionality of IDPs is thought to be associated with the amino acid compositional bias, which deprives the protein of its ability to fold but enables it to maintain multivalent interactions with other molecules.

IDPs were shown to participate in regulatory processes such as post translational modifications, transport, and regulation of gene expression by compartmentalizing molecules intracellularly through the process of liquid-to-liquid phase separation (LLPS). Recent discoveries have experimentally shown IDPs as being key regulators of phase separation in vitro and in vivo over the years; however, the molecular processes that govern IDPs to form phase separated droplets in eukaryotic cells remain largely unknown. The purpose of this research work was to establish a relationship between the amino acid composition and natively unfolded conformation of IDPs. Hence, the bioinformatic analysis of intrinsically disordered proteins in Drosophila melanogaster was performed to examine the distribution of disordered content and the amino acid compositional bias. Genetic line diagrams and a primer design strategy for the selected proteins were completed as part of the future work analysis. The findings of bioinformatic screening along with the future laboratory experiment will contribute to our understanding of molecular principles behind IDR-driven phase separation and its application in human disease.

Department

Biological Sciences

Faculty Advisor

Don Nelson

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In Pursuit of Phase Separation

According to Anfinsen’s structure-function postulate, the ability of linear chains of amino acids to fold into a 3-D structure governs protein’s function. Therefore, the subsequent recognition of intrinsically disordered proteins (IDPs) that fail to form a stable conformation, but yet preserve its biological function, became a “mysterious” phenomenon in protein science. Disorder-based functionality of IDPs is thought to be associated with the amino acid compositional bias, which deprives the protein of its ability to fold but enables it to maintain multivalent interactions with other molecules.

IDPs were shown to participate in regulatory processes such as post translational modifications, transport, and regulation of gene expression by compartmentalizing molecules intracellularly through the process of liquid-to-liquid phase separation (LLPS). Recent discoveries have experimentally shown IDPs as being key regulators of phase separation in vitro and in vivo over the years; however, the molecular processes that govern IDPs to form phase separated droplets in eukaryotic cells remain largely unknown. The purpose of this research work was to establish a relationship between the amino acid composition and natively unfolded conformation of IDPs. Hence, the bioinformatic analysis of intrinsically disordered proteins in Drosophila melanogaster was performed to examine the distribution of disordered content and the amino acid compositional bias. Genetic line diagrams and a primer design strategy for the selected proteins were completed as part of the future work analysis. The findings of bioinformatic screening along with the future laboratory experiment will contribute to our understanding of molecular principles behind IDR-driven phase separation and its application in human disease.

 

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