Eukaryotic development depends on three carefully orchestrated processes: differentiation, morphogenesis, and growth. In order to do so, the developing organism is responsible for regulating the spatial and temporal expression of the genes that are required for these events. The basic Helix-Loop-Helix (bHLH) transcription factor family regulates the expression of a number of these genes, often through regulatory cascades that rely on the proper responses to sensory signals provided by the environment. Members of the Johnson laboratory are interested in understanding the specific role of the bHLH family of proteins on neural development in the roundworm, Caenorhabditis elegans. In a previous NSF-supported study, graduate and undergraduate students identified and initiated a molecular study of one bHLH gene, hlh-17. The research to take place in the present study is designed to delineate more clearly the expression and biological activity of hlh-17 through two specific aims: (1) identify other bHLH proteins that are capable of interacting with and/or influencing HLH-17 using pull-down assays and the yeast two-hybrid system, and (2) determine if hlh-17 influences, or is influenced by, genes that regulate aging and longevity by using quantitative RT-PCR. This project should provide further insight into the role of HLH-17 in neurological behaviors of C. elegans, provide information on the possible roles of the mammalian homologs of HLH-17 in mammalian neural development, and provide further insight into one of the few bHLH proteins that is believed to act as a negative, non-DNA binding regulator of transcription. The broader impact of the project is that all of the research will be done at Morgan State University, a historically black institution located in Baltimore City, Maryland, by undergraduate student researchers and a Master's degree candidate (most of whom will be underrepresented minorities or women), all of whom will participate in local, national, and international research symposia. In addition, the Johnson laboratory has a long-standing tradition of involving students at all levels (K-12) in the research activities, through undergraduate student-led demonstrations at local elementary schools, through 4-6 week long PI-sponsored laboratory experiments with middle school students, and through high school/middle school student internships, a tradition that will continue with this project.
