Development of a live-cell HIF-1α reporter and characterization of single-cell HIF-1α signaling
Abstract/Contents
- Abstract
- Hypoxia inducible factor-1α (HIF-1α) is a crucial transcription factor required to regulate cellular responses to hypoxia, as well as large-scale metabolic changes in rapidly dividing cells and immune cells. Yet, despite the importance of HIF-1α, little is known about the dynamics of its activation at a single cell level. Here, I present my work to address this shortcoming. First, I review in detail some of the key characteristics of HIF-1α and its regulation of metabolism, as well as techniques for studying how single cells decode dynamic information. Next, I present my work developing a computational pipeline for high-throughput analysis of live-cell microscopy data, which was used to analyze all of the data presented here. Then I discuss the development and validation of a single cell HIF-1α reporter and present results characterizing the HIF-1α response of single cells through the lens of information theory. Further, I present observations of heterogeneous, dynamic patterns of HIF-1α in response to a physiological stimulus, interferon gamma. Finally, I present results from mathematical modeling of the downstream metabolic changes, revealing heterogeneity in the predicted metabolic phenotype of individual cells. In sum, my work contributes a valuable tool to the scientific community in the form of an optimized HIF-1α reporter, as well as novel observations and insights about the activity of HIF-1α at a single cell level.
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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Jeknic, Stevan |
|---|---|
| Degree supervisor | Covert, Markus |
| Thesis advisor | Covert, Markus |
| Thesis advisor | Bintu, Lacramioara |
| Thesis advisor | Bryant, Zev David |
| Degree committee member | Bintu, Lacramioara |
| Degree committee member | Bryant, Zev David |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Stevan Jeknić. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/hs255sn1263 |
Access conditions
- Copyright
- © 2022 by Stevan Jeknic
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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