Intellectual Merit: This project addresses an important fundamental question in biology. Is there a biological code of modifications on histone proteins that regulate gene expression patterns? Histones are small proteins that associate with DNA to form chromosomes, and individual site-specific post-translational modifications on the histones are associated with gene activation or silencing. However, the effect that simultaneous combinations of histone modifications have on gene activity is not known. The main reason for this lack of knowledge is that methods for quantitative characterization, or even qualitative identification, of combinatorial histone modifications by any standard biological technique do not exist. Towards this end, this research will develop novel mass spectrometry based proteomic methods and accompanying bioinformatics to quantitatively characterize combinatorial histone modification patterns and their influence on gene expression under different biological conditions in yeast. The integrated and transformative proteomic techniques developed by this project will be of immediate use to a wide range of scientists. Results of these experiments will be made publically available in a web based database hosted through the Lewis-Sigler Institute for Integrative Genomics at Princeton University. These studies in combination with biochemical experiments will help provide a systems biology outlook on gene expression that will lay the basic scientific foundation to advance several applications, such as cellular reprogramming.
Broader Impacts: This project will provide an introduction to genomics and proteomics to both educators and students (including minorities) at the community college level. Although there are many existing programs to support undergraduate and graduate research at the university level and to promote science to K-12 students, few such programs exist for community college students. Multiple opportunities will be made available. Strategic partnerships with local industrial collaborators have been created to initiate a mechanism of support for community college student summer research experiences. A summer proteomics workshop will be used to educate and train community college educators in theory and practice of modern proteomics research. This workshop will offer classroom lectures and laboratory training, allowing the attendees to prepare samples, acquire and interpret data and learn post-acquisition data processing. A website containing tutorials, reviews and other resources will be made freely available as an external means for the community college educators to continuously update their proteomics training upon returning to their campuses. Outreach initiatives will include recruitment of underrepresented students through participation in minority research conferences such as at the Society for the Advancement of Chicanos and Native Americans in Science, and through direct interaction with diversity programs (i.e. McNair Scholars) at other colleges.
This project is co-funded by CHE (Chemistry of Life Processes) and MCB (Genes and Genome Systems).
