Understanding and manipulating ganglioside biosynthesis

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Abstract/Contents

Abstract
The mammalian cell surface is comprised of a heterogenous mixture of proteins and lipids decorated by carbohydrates. These molecules are known as glycoconjugates. Among the many types of glycolipids imbedded within the plasma membrane is a class of negatively charged species known as gangliosides. Gangliosides, which are characterized by the presence of sialic acid residues, are responsible for regulating the activity of many cell surface proteins and serve as recognition targets for cell-cell communication and pathogen invasion. To investigate the biological roles of gangliosides in mammalian cells, I have employed metabolic oligosaccharide engineering techniques to introduce small structural changes into sialic acid residues. Using these methods, I have successfully demonstrated the biosynthesis of photocrosslinking gangliosides in mammalian cells. These photocrosslinking gangliosides can be used to capture and isolate transient ganglioside-mediated interactions in their native environment. I have also used metabolic engineering techniques to probe the substrate selectivity of ganglioside sialyltransferases in mammalian cells. My results illustrate significant differences in the ability of different cell lines to metabolize sialic acid analogs; these differences may be due species-specific variations in sialyltransferase specificity.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2010
Issuance monographic
Language English

Creators/Contributors

Associated with Whitman, Chad Michael
Associated with Stanford University, Department of Chemistry
Primary advisor Du Bois, Justin
Primary advisor Kohler, Jennifer, 1972-
Thesis advisor Du Bois, Justin
Thesis advisor Kohler, Jennifer, 1972-
Thesis advisor Khosla, Chaitan, 1964-
Advisor Khosla, Chaitan, 1964-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Chad Michael Whitman.
Note Submitted to the Department of Chemistry.
Thesis Thesis (Ph. D.)--Stanford University, 2010.
Location electronic resource

Access conditions

Copyright
© 2010 by Chad Michael Whitman
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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