My project has focused on understanding the structural organization of the clostridial neurotoxins, botulinum and tetanus, that are the causative agents of the neuroparalytic diseases botulism and tetanus. Once the toxins enter the bloodstream they inhibit the release of neurotransmitters required for the contraction or relaxation of muscles, resulting in debilitating paralysis. Botulinum neurotoxin is also orally toxic, whereas tetanus neurotoxin is not. Botulinum interacts with additional Clostridium botulinum proteins to form complexes that protect the neurotoxin from degradation as it passes through the hosts gastrointestinal tract. Using electron microscopy techniques, I have produced novel structural insights into the molecular organization of the three botulinum neurotoxin progenitor complexes responsible for human botulism. This dissertation also reports analysis of the tetanus holotoxin structure.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07022014-201713 |
| Date | 03 July 2014 |
| Creators | Benefield, Desirée Allyn |
| Contributors | D. Borden Lacy, Earl Ruley, Melanie Ohi, Timothy Cover, Eric Skaar |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07022014-201713/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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