Abstract:

Gene regulatory networks direct development, cell identity, and homeostasis. How some gene regulatory networks change from directing organ development in embryonic stages to supporting organ functions in juvenile and adult stages has not been sufficiently explored. Furthermore, the microbiome’s influence on the biology of organ systems is just beginning to be appreciated. This project aims to capitalize on the 20-cell Caenorhabditis elegans intestine as a model organ system to determine how intrinsic (gene regulatory network) and extrinsic (microbial) factors influence transcription over developmental time. This project will also support an outreach initiative to introduce community college students to diverse STEM fields, support them through the transfer stage, and assist them in gaining research opportunities in Computational Biology. American Rescue Plan funding of this project supports this investigator at a critical stage in her career.

The gene regulatory network that directs organogenesis of the C. elegans intestine is a classic model system. It culminates in ELT-2 (Erythroid Like Transcription factor), a highly conserved regulator. Using genomics approaches, the proposed work will test whether ELT-2 influences changing gene expression through autonomous mechanisms or in combination with dynamic partners. Specifically, the project will explore the relationship between ELT-2 and its homolog ELT-7. Intestinal microbes greatly impact intestinal biology, yet C. elegans are typically studied in isolation from natural microorganisms. A newly curated C. elegans microbiome resource (CeMbio) affords new opportunities to determine how microbes influence intestinal transcription. By investigating this at the single-cell level, the proposed work will determine how cell identity and the microbiome intersect. Overall, this project will illuminate how organ systems transcriptionally orchestrate biological processes with single-cell precision, over developmental time, and in response to the microbiome.