Systematic discovery of transcriptional effectors and integrases in human cells
Abstract/Contents
- Abstract
- To understand how thousands of DNA and protein factors interact to govern the expression of the human genome and to learn how to manipulate these functions to encourage cells towards healthy states, we need scalable quantitative methods to study these factors inside human cells. In this dissertation, I describe how high-throughput synthetic biology uncovers the functions of transcription factors, non-coding regulatory elements, and recombinases, which together advance our capacity to manipulate and understand the human genome and its regulation. First, I describe how CRISPRa/i perturbation tools can exhibit off-target toxicities when applied to test the function of non-coding sequences in the human genome, and how those toxicities can be mitigated. I then discuss a high-throughput protein function screen, HT-recruit, that enabled the systematic discovery of transcriptional effector protein domains. Lastly, I describe a computational approach that identified microbial recombinases for efficient large-payload genome editing. Together, these projects demonstrate how high-throughput synthetic biology can help identify functions of protein and DNA factors in human cells and improve technologies to precisely manipulate the genome and gene regulation.
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 | Tycko, Joshua |
|---|---|
| Degree supervisor | Bassik, Michael |
| Degree supervisor | Bintu, Lacramioara |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Bintu, Lacramioara |
| Thesis advisor | Greenleaf, William James |
| Thesis advisor | Porteus, Matthew H |
| Thesis advisor | Ting, Alice Y |
| Degree committee member | Greenleaf, William James |
| Degree committee member | Porteus, Matthew H |
| Degree committee member | Ting, Alice Y |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joshua Tycko. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/yf501km3807 |
Access conditions
- Copyright
- © 2022 by Joshua Tycko
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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