Thesis Christ: Disrupting Zebrafish Genes with Miranda Ulloa Estrada

For many students, the fall semester is just coming into full swing, with the first papers and exams only around the corner. Yet the all-consuming thesis grind is well underway for Spring/Fall seniors, bringing with it another year of the Quest’s Thesis Christ column. Starting off this year’s coverage, Spring/Fall Biology senior Miranda Ulloa Estrada spoke to the Quest about her thesis on gene editing and development in zebrafish.

Estrada’s research makes use of the gene-editing tool CRISPR to study how disrupting genes creates changes in zebrafish growth and development. This involves a technique called microinjection, where CRISPR is injected directly into the zebrafish embryos. Specifically, Estrada focuses on changes in the gene tshz1a, or “teashirt,” which is related to head and ear development. 

In the spring, Estrada mainly tested the CRISPR procedure by working on another gene, golden. When disrupted, the golden gene removes pigment from the zebrafish’s eyes. This effect is a useful test for whether CRISPR is working as intended. “It’s nice in science sometimes to see something have a visible change,” remarked Estrada.

However, Estrada’s thesis research hasn’t always been so flashy. “I had to learn a lot about the breeding of zebrafish before I was even able to do my thesis,” said Estrada. “For the first couple of weeks, I was just trying to get my zebrafish to lay eggs.”

At this point, Estrada is focusing primarily on disrupting the teashirt gene. Her work now consists of finishing the data collection process and running follow-up experiments on the effects of teashirt on other gene expression patterns. Throughout this process, Estrada has been working with Professor Kara Cerveny as her advisor. “She’s awesome and really helpful with navigating learning new techniques like microinjection,” said Estrada on Cerveny’s assistance. 

Research with zebrafish can have wider implications for human gene research. Many of the genes found in humans can also be found in zebrafish. Specifically, mutations of the teashirt gene, which Estrada disrupts in her thesis research, are linked to aural atresia, a condition in humans where the ear is not fully developed. She explained, “By studying tshz1a [teashirt] in zebrafish and how it interacts with developmental pathways, we hope to uncover new insights into how such congenital diseases occur.” In this way, Estrada’s thesis connects to wider possibilities in human gene research.

Estrada expressed optimism about the opportunities presented by her thesis. “I think it’s a good preparation for grad school and it’s definitely a test of doing lab work independently,” she noted. To future thesis students, Estrada offered these words of advice: “If you’re failing, you’re getting results, you’re getting data, you’re knowing more because you’re doing things that haven’t been done before. That’s the difference between doing a lab and doing a thesis.”