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Mammals are able to perceive and discriminate amongst a huge variety of different smells by using olfactory receptor proteins to detect chemical odorants. The olfactory receptor gene family underwent a massive expansion when animals moved onto land allowing terrestrial animals to smell a huge diversity of airborne odorant molecules. Mammalian genomes now encompass hundreds of genes, and elaborate gene regulatory mechanisms have evolved to regulate their expression in sensory neurons. The goal of this project is to determine when these specialized regulatory mechanisms evolved, and the relationship between these mechanisms and the expansion of the olfactory receptor gene family.
in most species of mammals. Olfactory receptor proteins are expressed by olfactory sensory neurons in the main olfactory epithelium. Each olfactory sensory neuron is specialized in that it expresses only one type of olfactory receptor out of the hundreds it could potentially choose from. This receptor choice happens at the level of transcription; a single allele of one receptor gene is transcribed while the hundreds of other genes are kept transcriptionally silent. We have shown that this singular gene choice involves dramatic changes in the 3D structure of the nucleus and in the packaging of olfactory receptor genes into chromatin. We want to know how each olfactory neuron chooses a receptor to express and how receptor choice is connected to processes that control sensory neuron differentiation. To accomplish this, we combine mouse genetics with molecular and genomic analysis of olfactory neurons in vivo.
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