Coming to graduate school, I knew I wanted to do translational work but in a basic biology context because I wanted to understand the biology behind most diseases. CMDB attracted me because of the rotations during the first year. This process gave me the opportunity to explore different types of research like using optical tweezers to understand protein folding, performing microbiota analysis in Drosophila, or injecting CRISPR-Cas9 guide RNAs to edit the zebrafish genome. The faculty of the labs encouraged my ideas for possible projects and were understanding of my personal life outside of the lab. However, out of all my rotations, the Jimenez lab was one that stuck out to me the most because of the molecular biology focus to study regeneration of the inner ear.
The Jimenez lab uses high-throughput sequencing methods to understand the molecular response that occurs during regeneration of the zebrafish inner ear. Humans and zebrafish alike contain hair cells, rectangular long shaped cells with stereocilia on top which allows for mammals and nonmammals to receive and process sound. My scientific experiences in undergraduate training were mainly in cell culture, using HeLa cells to understand metastasis, so moving to a living organism, the zebrafish was a new territory that I was excited to experience. The developmental biology class piqued my interest even more with presentations over current research in zebrafish that overlapped with the developmental concepts being taught in class.
My thesis work focuses on regeneration responsive elements (enhancers) and their control in gene regulatory networks in adult zebrafish. Previous single-cell RNA and ATAC sequencing data from the lab captured cell-specific transcription factor (TF) motif patterns in the chromatin that opened specifically during regeneration. This emergent enhancer activity with differential gene expression to identify key gene regulatory networks driving regeneration. Using pseudo-time analysis of single-cell transcriptomic data, we showed that the support cells within the sensory epithelium changed cell identity to a more pluripotent “progenitor” cell population that could either proceed to differentiate into new hair cells or return to a support cell identity. Although gene regulatory networks were identified using single-cell technology and computational analysis on dissociated cells, these techniques inherently lack spatial resolution and three-dimensional information of gene responses in their native heterogeneous tissue architecture. My work will explore further how regeneration responsive elements maintain the transcriptional landscape of each of the cell types and its role in regulating gene expression responses through spatial in situ hybridization technology to generate a molecular atlas of the regenerating inner ear.
Outside of the lab, the friends I have made in CMDB have been my greatest support system. The transition from undergraduate to graduate school is tough, but my cohort members kept me motivated. Deciding a thesis lab and studying for exams became an easier task when I had cohort members to share the experience. The post-docs, lab technicians, and undergraduate researchers within the department are also willing to lend a hand and offer advice. Here, you are around people who are doing amazing science while being your number one fan.