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Joseph Jez, PhD Summer Lab Size: Local Summer Program: http://dbbs.wustl.edu/divprograms/SummerResearchforUndergrads/Pages/BiomedRAP.aspx Program Dates: May 30-August 5, 2017 Washington University in St. Louis Biochemistry, Structural Biology Exploring Biochemical Regulatory Networks in Plants and Microbes EXROP students can fit into any of the three major projects in the lab, all of which use a combination of biochemical and structural biology approaches. Specific projects can be tailored to fit the background and expertise of a student but typically include molecular cloning, protein expression and purification, biochemical assays, and protein crystallization. Some projects also include plant genetics using Arabidopsis thaliana as a model organism. 1. Metabolic Regulatory Networks and Environmental Responses A fundamental challenge for biologists is to understand how organisms respond to their environment to maintain growth, development, and propagation.Environmental changes lead to multiple adjustments across metabolic, signaling, and gene expression pathways.A major goal of this research is to develop a molecular view of how key regulatory proteins function in the context of metabolic networks and cellular localization using structural biology and biochemical approaches. 2. Enzymatic Control of Plant Hormone ResponsesPlant development, growth, and fitness are all determined by the complex integration of multiple signaling pathways and hormone responses; however, perception by receptors is only one piece of this biological puzzle. As part of the system that regulates plant hormone effects, GH3 proteins control levels of major plant hormones, including jasmonates and auxins, and modulate pathways for plant growth and development, seed development, light signaling, drought response, and pathogen resistance. Structural and mechanistic investigations are required to understand how these proteins catalyze hormone modifications and to decipher the determinants of both acyl acid and amino acid substrate specificity that allow GH3 proteins to modulate a wide range of plant hormone action. 3. Lessons from Plant Metabolism: Antiparasitic Targets The worldwide impact of parasites on human, animal, and plant life is profound.As drug-resistant strains of parasites emerge, there is an urgent need to identify new biochemical targets for developing antiparasitic compounds. Our studies suggest that Caenorhabditis elegans and other nematodes, unlike other animals, use a plant-like pathway as the major biosynthetic route to phosphatidylcholine. In this pathway, a pair of phosphoethanolamine methyltransferases (PMTs) catalyze the sequential methylation of phosphoethanolamine to phosphocholine, which can be incorporated into phosphatidylcholine.Because the PMTs are highly conserved across nematode parasites of humans, livestock, and plants, as well as in protozoan parasites, understanding how these enzymes function and the identification of inhibitors will aid in the development of new antiparasitic compounds of potential medical, veterinary, and agricultural value. This project aims to explore and characterize the PMTs for the development of antiparasitic compounds.