Xu Lab
Research
Protein Folding and Translocation | Bacterial Pathogenesis | Insulin Signaling and Diabetes | Membrane Biosynthesis
Structural Biology
At the Xu lab, the emphasis is on biological molecules and how they function. Dr. Xu seeks fundamental insights into the ways in which living systems function and evolve at the molecular level. 
From in vivo protein folding and translocation to bacterial pathogenesis to insulin signaling and diabetes, Dr. Xu's lab covers a wide range of important areas of modern biology. His research is heavily focused on molecular structure with particular emphasis on X-ray crystallography. With its strong ties to both the Medical School and the College of LS&A, the Xu lab at the Life Sciences Institute demonstrates a broad interest in many structural aspects of biology. The medical connection, which allows for collaborative research projects in human health, makes its research program unique.
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Protein Folding and Translocation
Understanding protein folding is one of the most challenging questions facing scientists in the coming decades. Cellular synthesis of polypeptides is an amazing, complex, and efficient process. Each newly synthesized protein, however, must be folded into its correct tertiary structure and transported to the correct cellular location for proper function. Improper folding and translocation of proteins has been implicated in many disease states. A class of protein molecules known as molecular chaperones ensure that newly synthesized polypeptides are properly folded into their active forms and transported to their intended destination in the cell. Analysis of the folding pathway of newly synthesized proteins in both prokaryotic and eukaryotic cytosols reveals that molecular chaperones function at almost every step in the pathway. Our goal is to understand the underlying principle that governs the functions of chaperones in the cell.
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Bacterial Pathogenesis
Of all the known bacterial species, only a few are pathogenic to humans. But these few can be very deadly, like the Black Death or Plague which wiped out over one-third of the population of Europe during the Middle Ages. Interest in Plague has intensified recently because of the emerging threat of bioterrorism. The disease is caused by the gram-negative bacteria Yersinia pestis. An important factor in the virulence of Y. Pestis is its ability to survive and proliferate inside the immune system's phagocytic cells rather than be killed by them. One of the ways this is accomplished is by the Yops (yersinal plasmid-encoded outer membrane proteins) that counteract natural defense mechanisms, effectively blinding the phagocytes to their presence, and helping the bacteria multiply and disseminate in the host. Recent advances in the field showed that Yop molecules are structurally and functionally diverse, including protein kinases, protein phosphatases, proteases and GAP molecules. The lab's goal is to understand the molecular mechanisms by which various Yop molecules function in human cells and how to defeat them.
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Insulin Signaling and Diabetes
Diabetes constitutes a worldwide epidemic, with an estimated 143 million people worldwide having the disease. Type 2 diabetes is the more common form of the disease. It results from a combination of defects in both secretion and action of insulin, the hormone that regulates the blood sugar level. When the blood sugar level is high after a meal, insulin will stimulate a cell to allocate more glucose transporters to its surface pumping more glucose into the cell and therefore reducing the blood sugar level. This stimulation process is accomplished by several intracellular signaling pathways, where different protein molecules interact according to a defined temporal and spatial order. Errors in this process will have serious undesirable consequences including type 2 diabetes. Understanding what these protein molecules look like and how they interact will provide an important chemical foundation for future drug designs. Working closely with Alan Saltiel's lab, the Xu lab's goal is to use the power of structural biology to unveil the structures and interactions of several important protein molecular complexes in the insulin signal transduction pathway.
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Membrane Biosynthesis
Phosphatidylcholine is a predominant structural component of the membrane bilayer, pulmonary surfactant, and serum lipoproteins, and it participates in signaling pathways. The biosynthesis of phosphatidylcholine is regulated by two enzymes, choline kinase and CTP:phosphocholine cytidylyltransferase. Certain bacterial pathogens and some lower eukaryotes contain phosphocholine attached to cell wall components. Genetic evidence suggests that a CDP-choline pathway, similar to the eukaryotic pathway for phosphatidylcholine biosynthesis, is involved in attaching phosphocholine to the cell wall. The lab's goal is to characterize the structure of choline kinase and determine how its activity is regulated both in vitro and in vivo.
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