Author: Michelle Franc Ragsac
University: University of California, San Diego
Department: Bioinformatics & Systems Biology (https://bioinformatics.ucsd.edu/)
- Professor Emma K. Farley, Chair
- Professor Theresa Gaasterland, Co-Chair
- Professor Vineet Bafna
- Professor Christopher Benner
- Professor Xin Sun
Embryonic development across all vertebrates begins upon the fertilization of an egg by a sperm cell to become a single-celled zygote. Embryogenesis continues with various stages of division to eventually make up an entire organism. The processes governing development are finely orchestrated and include many participants, such as genes involved in gene regulatory networks and non-coding regions of DNA, or enhancers, to regulate the expression of those genes. Defects or perturbations to this strictly regulated machinery can lead to various clinical conditions, such as congenital heart disease. Thus, deepening our understanding of embryogenesis may help us understand the mechanisms driving congenital abnormalities as well as the evolution of developmental pathways. One defining characteristic of all chordate embryos is the presence of a notochord during development. The notochord is a long, semi-rigid fibrous rod of mesodermal origin that provides structural support and serves as a signaling center to pattern the neighboring neural tube, paraxial mesoderm, and gut. A complete understanding of notochord structure and function during early and late life stages is thus essential to better understand congenital vertebral defects. For example, failure of vertebral notochord cells to transition to the nucleus pulposus, the cushioning between intervertebral discs of the spine, is associated with chordomas, slow-growing tumors formed from notochord cell remnants within the spine or the base of the skull. The ascidian Ciona intestinalis Type A (Ciona) is a marine organism that is evolutionarily similar to vertebrates. Through electroporation, Ciona is readily amenable to high-throughput, high-resolution functional studies of cis-regulatory elements like enhancers in their native, whole-embryo context. To identify key notochord enhancers, I analyzed the importance of enhancer grammar–the transcription factor order, orientation, spacing, and binding affinity–in modulating notochord-specific expression. Next, I highlight the potential of single-cell RNA-sequencing to study the gene regulato ry networks governing notogenesis and their relationship to congenital abnormalities. This body of work provides new insight into the regulatory processes governing notochord development, providing direction for future efforts to improve our understanding of notochord-based diseases across chordates. Finally, I highlight Open Educational Resources (OERs) I developed for Bioinformatics education, emphasizing accessibility and inclusion.
My dissertation can be found online on eScholarship under identifier 1471r9g0: https://escholarship.org/uc/item/1471r9g0.
On that page, it is possible to download the official PDF document, but I have also included it within this repository!
Ragsac, M. F. (2022). Decoding the genomic regulatory syntax driving notochord development. UC San Diego. ProQuest ID: Ragsac_ucsd_0033D_22000. Merritt ID: ark:/13030/m5z39b30. Retrieved from https://escholarship.org/uc/item/1471r9g0
This dissertation document was generated with LaTeX, a typesetting program that is commonly used across multiple academic disciplines.
As I am working in MacOS, I used the MacTeX distribution, but you can download the versions for Linux and Windows (TeX Live for both systems, or MiKTeX for Windows). There are also online versions of LaTeX, such as Overleaf, that are easily accessible!
I wrote the text for my dissertation in Google Docs to make things easily accessible for my committee, then I would export the text to edit the .tex files for each chapter in Visual Studio Code (VS Code).
I also used the following tools to make the writing process easier:
- LaTeX Language Support for Visual Studio Code
- LaTeX Workshop Visual Studio Code Extension
- Better BibTeX for the Zotero Reference Manager
- Zotero LaTeX Visual Studio Code Extension
Tip
I wrote my dissertation in 2022 and since then, there have been updates to various reference managers (such as PaperPile) that allow for efficient exporting of documents with embedded references to the .tex format!
There have also been updates to the dissertation requirements, so always remember to the Division of Graduate Education and Postdoctoral Affairs website on "Dissertation and Thesis Submission" to make sure you're following university guidelines.
My dissertation document references the template that can be found at the following GitHub repository: https://github.com/stevecheckoway/ucsddissertation.