CAREER: Priming CUREs to dissect how the DREAM complex protects cell identity

Michigan Technological University, Houghton MI

Investigators

Abstract

Cellular identity is controlled by protein networks that establish which genes are expressed in a cell. These protein networks react to internal and external signals and define how the cell functions within the context of a multicellular organism. A major obstacle in the field is that mechanisms that govern cell identity are remarkably complex, such that identifying the contributing factors remains a challenge. Identifying the missing components is critical for generating an integrated view of how specialized cell types develop. This project will fully integrate bioinformatic and experimental life science focused Course-based Undergraduate Research Experiences (CUREs) within the research activities to identity novel factors involved in establishing cell identity. Overall, the CURE efforts will offer undergraduate students access to research and will help them develop the skills required to become competitive in their future life science careers. In Caenorhabditis elegans, the DREAM (for Dp, Retinoblastoma(Rb)-like, E2F, and MuvB) complex suppresses the differentiation programs in somatic (non-reproductive) cells, preventing them from activating the germ (reproductive) cell program, and also preserves the normal specification of vulval cell fate. DREAM represses genes through direct binding to their promoter regions, but no evidence indicates that the complex targets genes known to be associated with cell identity. These observations lead to the hypothesis that loss of the DREAM complex likely activates transcriptional components that drive breakdown of somatic cell identity. By creating improved reporter strains using CRISPR/Cas9-mediated genome editing in the laboratory with reverse genetic screens performed in the classroom, this proposal aims to reveal key components that contribute to normal germline and vulval development. In addition, the central role the DREAM complex plays in the regulation of cell identity in C. elegans offers an opportunity to explore how such developmental programs are conserved across multicellular organisms. Using bioinformatic conservation analyses and molecular genomics, this proposal will explore DREAM co-conservation with the intent of building a manual gene curation pipeline for identifying and annotating genes-of-interest in published but under-annotated genomes. Overall, this research will contribute to understanding the mechanisms by which transcriptional regulatory networks determine cellular and organismal diversity. This proposal was co-reviewed and will be co-funded by the Genetic Mechanisms Cluster in the Division of Molecular and Cellular Biosciences and by the Developmental Systems Program in the Division of Integrative Organismal Systems. 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.