EAGER: Toward engineering a synthetic enhancer in Caenorhabditis elegans

Title: EAGER: Toward engineering a synthetic enhancer in C. elegans Senior Personnel: Ilya Ruvinsky, PI, Northwestern University Overview: Employing a combination of experimental and computational approaches, this project will investigate the fine-scale organization of enhancer elements in a model organism C. elegans. This work is motivated by a hypothesis that certain kinds of regulatory elements are systematically under-discovered. Successful completion will improve understanding of gene regulatory mechanisms, facilitate research in neuronal development, and inform comparative genomics approaches. Broader Impacts will specifically promote broader participation in research of students from traditionally underrepresent groups and facilitate teaching and training. INTELLECTUAL MERIT The cis-regulatory elements that direct gene expression have been studied for decades. Although a great deal is known about thousands of these enhancers from a wide variety of species, relatively few have been dissected with great precision revealing all transcription factor binding sites that constitute them. Moreover, the tools commonly employed to study enhancers may preferentially discover some kinds of sites over others. This situation hinders the understanding of general principles of cis element organization and limits the application of the powerful tools of comparative genomics. Experiments proposed here are specifically aimed to address these problems. The Ruvinsky Laboratory at Northwestern University has an established record of using C. elegans as a model system to study enhancer function and evolution. Specifically, the PI developed three research directions: (1) To systematically discover functional elements within several C. elegans enhancers, particularly focusing on those sites that are less likely to be found using traditional methods. (2) To test a hypothesis that breadth of expression of a gene is reflected in the compositional properties of its enhancer. (3) To use the newly-obtained functional data to reevaluate patterns of sequence conservation and divergence within enhancers. This work promises to improve understanding of enhancer organization and function and will contribute to the study of developmental biology and comparative genomics. BROADER IMPACTS are motivated by PI’s long-standing commitment to research and mentorship in genetics, development, and evolution, and to community outreach to communicate the results. They are developed along three main directions. 1. Broadening participation is accomplished by communicating to teachers recent findings in biology and recruiting them to participate in research. This creates new opportunities for STEM learning for students in Chicago School District, which serves a large population of students traditionally underrepresented in science. In addition to better classroom learning promoted by teacher engagement, the PI recruits students to work in his lab offering them a chance to practice science. 2. Dissemination is accomplished by (A) developing tools and resources used by the broader research community and by (B) communicating results to colleagues and the public via open-access publishing and presentations. 3. Promoting teaching, training and learning is achieved by (A) PI’s mentorship, recognized by a University-wide award and (B) By creating an interdisciplinary research environment conducive to training at all levels – from high school students to postdocs. Key words: C. elegans, gene regulation, transcription, cis-regulatory elements, evolution