CAREER:Investigating Heterochromatin Assembly through Histone Deacetylases

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The way that the genome of a cell is "packaged" inside the nucleus directly impacts genome stability and DNA-templated processes such as gene expression and replication necessary for cell division. Highly condensed DNA structures are inhibitory to such processes, and their formation is a critical part of regulatory mechanisms. Despite the important biological roles, little is known about how regions of highly condensed DNA, called heterochromatin, form. This CAREER project will elucidate and compare the molecular pathways necessary for the formation and propagation of functionally distinct heterochromatin domains. Exploiting unique features of the ciliate model Tetrahymena thermophila, Dr. Wiley and a team of undergraduate students will specifically explore the role of histone deacetylase (HDAC) enzymes in heterochromatin formation by determining their spatial and temporal localization and by analyzing mutant cells. Using HDACs as molecular handles, students will employ standard molecular techniques to isolate and identify proteins that bind to them in complexes and further analyze these proteins as candidate components of the pathways. The project's design will significantly increase the number of undergraduates participating in original research. Locally, the work will serve as the foundation of a new laboratory course for sophomore level students, and for numerous mentored student research projects. To extend the research opportunities to undergraduate students at other institutions, the relevant protocols and methods will be packaged and disseminated as classroom laboratory activities for easy integration into existing curricula. Student researchers from all institutions involved will disseminate and discuss their results with the broader scientific community through an interactive website/database linked to the Tetrahymena Genome Database at Stanford University. This project contributes directly to our understanding of a central question in molecular biology that underlies processes essential for life -- how genomes portray and regulate the information that governs cell characteristics. It will enhance our understanding of genome dynamics, make important contributions to the annotation of a recently sequenced genome, and will also provide to the larger scientific community, valuable reagents for further genome research. Through this multi-institutional initiative, many teams of students will participate in the collaborative research network and be part of a powerful scientific learning community based on the excitement of original research, all at an important time when they are making career decisions. This experience should encourage students to persist in their science education and be particularly supportive of historically underrepresented groups. Increasing the accessibility of science for all students is critical to ensuring future technological advancements and continued economic vitality upon which our high standard of living and the development of other nations depend.