Immediately following animal fertilization, embryonic cells undergo rapid cell divisions to make a multicellular organism. Precise equal separation of duplicated DNA into two daughter cells is crucial during early development. If tight regulation of cell divisions does not occur in the early embryo, it can cause developmental defects, birth defects, or embryo death. This project investigates the regulation of cell divisions, mediated by a small RNA called microRNA-1 (miR-1). Using sea urchin embryos and mammalian cells as models, the project will use innovative live imaging and genetic approaches to decipher how miR-1 regulates cell division, a biological process used by all living organisms. Because miR-1 is a highly conserved microRNA, this project enhances biotechnology by applying knowledge gained in a simple marine organism to understand cell divisions and muscle tissue development in higher animals. Furthermore, using bioinformatics and artificial intelligence-driven approaches to annotate protein domains and functions, the research team will identify additional novel functions of miR-1 to advance the field of cell and developmental biology. In addition, the project provides a framework for research training and educational outreach activities for undergraduate and graduate students in STEM, as well as empowering future early childhood teachers in science instruction to foster scientific interest in young children.
The project goal is to examine how post-transcriptional regulation mediated by miR-1 fine-tunes mitosis, using sea urchin embryos and mammalian cells. The overarching hypothesis is that miR-1 mediates chromosomal segregation and mitotic spindle structure during embryonic mitosis. The function of miR-1 will be examined through use of sophisticated genetics reagents, live imaging, and novel in-cell proteomics approaches. The research team will identify miR-1 targets using both candidate and unbiased, innovative “efficient, effective, economical, and enhanced” (E4) mass spectrometry to detect proteomes from a small number of experimentally manipulated embryos. Overall, this study will serve as a paradigm for understanding post-transcriptional regulation mediated by microRNAs during mitosis, a fundamental and highly regulated cellular process used by all eukaryotic cells and organisms.
This award reflects NSF’s statutory mission and has been deemed worthy of support through evaluation using the Foundation’s intellectual merit and broader impacts review criteria.