Within an organism, every different type of cell contains the same set genes, but only a subset of these genes are on. This gives rise to the many different types of cells. Over many years scientists have made progress in understanding how the packaging of genes into an open or closed formation determines whether the gene will be on or off. This is a fundamental part of biology. However, scientists still have very little understanding of what happens when these mechanisms go awry and different cell type programs are competing against one another. The microscopic worm C. elegans has a unique feature where every cell type is made exactly the same way in every embryo. This provides a unique opportunity to address this question. The Katz Lab will take advantage of the invariant embryo in these worms to learn the rules governing how cells respond when an incorrect program is activated alongside the normal program. This will address a fundamental aspect of biology with wide ranging implications for many different and important processes.
Using C. elegans, the Katz Lab discovered that the H3K4me2 demethylase, LSD1, acts along with the H3K9 methyltransferase, MET-2, as an epigenetic reprogramming switch, replacing the active histone modification, H3K4me2, with the repressive modification,H3K9me2, at fertilization. In spr-5;met-2 mutants, the inappropriate inheritance of histone methylation leads to the ectopic expression of ∼200 critical germline genes in somatic cells, resulting in developmental delay. This model provides a unique opportunity to understand how inappropriately inherited chromatin affects transcription and how the expression of one developmental program affects cells trying to specify a different developmental program. To address this question, the Katz Lab will take advantage of the invariant C. elegans lineage to determine how chromatin, gene expression and cell fate are affected with single cell resolution in spr-5;met-2 mutants. This project is highly complementary to broader impacts pursued by the Katz Lab. Over the past 5 years of NSF funding, the Katz Lab at Emory University has partnered with a nearby liberal arts college, Oglethorpe University, to establish a Pipeline Course Embedded Undergraduate Research (CURE) curriculum, where biology majors take part in C. elegans research reiteratively throughout the biology major. This culminates in a Capstone Course, led by a postdoctoral fellow from the Katz Lab, where students spend the bulk of their class- time over a semester on an original C. elegans research project related to ongoing experiments in the Katz Lab. Because of the Pipeline CURE, the majority of biology majors now participate in authentic research, and initial surveys indicate that this authentic research can recapitulate the experience that is typically only found in an apprentice style approach at a major research university. To continue to lower the bar of accessibility to authentic research at a liberal arts college, the Katz Lab now proposes to provide every biology major the opportunity to conduct thesis research performed entirely in the classroom at Oglethorpe University.
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.
