When membranes collide : studying vesicle fusion using a model system based on DNA hybridization
Abstract/Contents
- Abstract
- Membrane fusion consists of a complex rearrangement of lipids and proteins that results in the merger of two lipid bilayers. This fusion reaction is central to many biological processes, including endo- and exocytosis and the transfer of membrane proteins between cellular compartments. The process of vesicle docking and fusion is mediated by formation of the SNARE protein complex, made up of recognition partners on the vesicle and target membranes, with many other accessory proteins assisting or regulating the process. Although extensively studied, essential questions about vesicle fusion, including the number of components involved and the precise physical mechanism, are not well understood. Due to the complexity of the fusion reaction and the proteins involved, reductionist model systems can complement in vivo data to yield a better understanding of this biological process. This dissertation describes the development and study of a reductionist model system that employs synthetic DNA-lipid conjugates as surrogates for the SNARE machinery. This model system affords easy control over DNA sequence, binding geometry, and length—factors less easily probed in SNARE-mediated fusion—and it allows us to examine how fusion proceeds once the vesicle and target membranes are brought close together in the absence of accessory factors. Previous work has demonstrated that hybridization of complementary DNA-lipid pairs on different vesicles can enable fusion between small vesicles in bulk. This dissertation expands upon that previous work to develop assays to study DNA-mediated vesicle fusion on the individual event level. These assays are then used to ask mechanistic questions about the DNA-mediated fusion reaction that were not previously addressable.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Rawle, Robert James |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Brünger, Axel T |
| Thesis advisor | Cui, Bianxiao |
| Advisor | Brünger, Axel T |
| Advisor | Cui, Bianxiao |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Robert James Rawle. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Robert James Rawle
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