Illuminating cellular processes : developing new optic techniques to investigate cellular communication and translational control
Abstract/Contents
- Abstract
- The human body comprises trillions of cells. Within single cells, complex cellular activities are precisely executed by millions of diverse proteins translated by the ubiquitous translational factory ribosome. How ribosomes control translation of each individual protein within subcellular space therefore dictates the cellular protein landscape at the nanometer resolution. Meanwhile, at the intercellular level, intricate cellular communication is required to coordinate individual cells to perform complex physiological activities. How trillions of cells achieve precise communication through the intertwined signaling network therefore dictates the physiological outcomes at the organismal level. However, direct visualization of these cellular processes has been technically challenging due to the lack of tools with the required spatial resolution. Here, I present novel optical innovations to spatially investigate cellular communication and translational control, respectively. In the first project, I develop an optogenetic toolbox to manipulate cellular communications using artificial myosin motors. Utilizing this toolbox, I am capable of directly probing the molecules transported within long cellular extensions and controlling the dynamics of both filopodia and neurites. I further demonstrate the presence and importance of specialized filopodia in the re-establishment of a Sonic Hedgehog signaling gradient during axolotl limb regeneration. In the second project, I investigate translation control within subcellular space with two orthogonal approaches. Specifically, I develop an optimized expansion microscopy technique to visualize individual ribosomes and an optogenetic proximity-labeling technique to characterize their composition. Utilizing both techniques, I unveil enrichment of the 60S large subunit on the endoplasmic reticulum that is critical for the selective translation of transmembrane proteins. I further discover ribosomal heterogeneity on the mitochondria that is linked to the translation of metabolism-related transcripts. Taken together, these advancements in optic techniques empower us to shed light on cellular processes at different scales with unprecedented resolution.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Zhang, Zijian |
|---|---|
| Degree supervisor | Barna, Maria |
| Thesis advisor | Barna, Maria |
| Thesis advisor | Boettiger, Alistair |
| Thesis advisor | Ferrell, James |
| Thesis advisor | Jarosz, Daniel |
| Degree committee member | Boettiger, Alistair |
| Degree committee member | Ferrell, James |
| Degree committee member | Jarosz, Daniel |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Chemical and Systems Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Zijian Zhang. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/wr897sw8025 |
Access conditions
- Copyright
- © 2023 by Zijian Zhang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...