Intellectual merits of this project: The genome is the cardinal instrument of development that encodes the genetic parts and genetic programs of an organism. With the sequencing of many genomes now complete, and indeed, most if not all the genes identified, a next great frontier in the quest to understand the relationships between genotype and phenotype is to decipher how genetic information is regulated. This frontier encompasses two essential biological attributes: regulatory code "hardwired" in genomes that specify when, where, and under which conditions each gene will be expressed, and epigenetic influences that specify biological context to which a genome responds. This project investigates a complex odorant receptor gene regulatory system that is likely to reveal both novel genetic and epigenetic properties of the genome, and thus provide additional insights into how transcriptional regulation is coordinated genome-wide. In order for the olfactory system to function properly, the >1000 odorant receptor genes clustered at multiple chromosomal locations must be co-regulated such that each sensory neuron of the nose expresses only one of these genes. In this research, we will use an in vitro model system to study the mechanisms that stabilize mutually exclusive OR expression in developing sensory neurons. We also investigate a novel discovery about the regulation of OR mRNA export during development.
Broader impacts of this project: Wesleyan University has an exceptional academic environment for teaching and scholarship, because it uniquely combines a highly selective undergraduate program with the research resources of a much larger institution. Within Wesleyan's new Integrative Genome Science program, this project will integrate research on genome regulation with course materials on these same topics. In addition, Wesleyan University embraces cross-disciplinary opportunities that contribute to a well-rounded, integrated liberal arts education. This project will provide undergraduate and graduate students at Wesleyan with a variety of scientific experiences, spanning fields of evolutionary biology, genomics, bioinformatics, molecular biology, genetics, and neuroscience. Thus, this project aims to advance integrated approaches in science that foster broader modes of thinking and approaches to problem solving. In addition to addressing specific questions pertaining to the field of olfaction, this project will potentially provide more wide-scoping insights into the functional organization of genomes, and epigenetic contributions to gene co-regulation and cell differentiation. The development and characterization of an olfactory sensory neuronal cell culture system will be of particular interest to the neuroscience community, especially in consideration of the fact that olfactory sensory neurons are one of the only known central neuron types in mammals that are capable of regeneration throughout the life of an organism. In summary, the research and educational components of this project will contribute to our understanding of olfactory development, genome organization, and gene regulation, and will contribute to the development of interdisciplinary research fields and inquiry-based science education.