Cell division is arguably the most dynamic event to occur during development. Multiple subcellular processes must be coordinated in order to ensure the correct segregation of cellular materials and the successful completion of cytokinesis. For instance, the nuclear envelope, which is intact during S-phase ensuring the proper completion of DNA replication, breaks down completely by the time the chromosomes are aligned at the metaphase plate. This breakdown is essential in order that the spindle microtubules may contact the condensed chromosomes and pull these to their appropriate poles. Very little is understood about how the formation and breakdown of the nuclear envelope is coordinated with DNA replication and chromosome segregation. Understanding the relationship between chromatin maintenance and nuclear envelope dynamics will reveal general principles whereby the multiple concurrent events that occur during cell division are managed. Dr. Fernandez has identified a novel AT-hook domain protein called MEL-28 (ELYS in vertebrates) that is required for both nuclear envelope function and the proper regulation of chromatin morphology and movement. This project will perform functional studies of MEL-28 in order to better understand how this protein coordinates two distinct processes.
Intellectual Merit: The coordination of simultaneous subcellular processes is key to the successful completion of cell division, thus understanding better how this is accomplished is essential to understanding how cells divide. Dr. Fernandez has shown that MEL-28 is required for the structural and functional integrity of the nuclear envelope and for the proper morphology, condensation state, and positioning of the chromatin. However, as MEL-28 is a large protein with few conserved domains, it is still largely unknown how the MEL-28 protein functions to accomplish these tasks. Thus this work will lead to understanding how an essential yet novel protein functions in its fundamental role in cell division.
Broader Impacts: Fundamental to understanding our natural world is not just to learn facts about it, but to understand where these facts come from. The best way for students to understand the scientific method is to spend time in a research setting as an active participant. Fairfield University undergraduate students will perform the experiments described in this proposal, gather empirical data from these experiments, and interpret these data to determine whether they support or refute our hypotheses. For many students, this will provide their first exposure to original research. Training students to engage research in this manner will make them better scientists. More importantly, these activities will help students develop into better thinkers and thus citizens more capable of making thoughtful decisions about how to run our society.
