Karl Keat, a junior studying biology and computer science at the University of Virginia, developed tools for identifying olfactory receptor ligands using single nucleus RNA sequencing.
Decades of literature have shown that the maternal diet affects amniotic fluid composition, resulting in the cultivation of early flavor preferences in offspring. The Broad is a truly special place where you not only find the world’s brightest, but also the most welcoming, helpful people you’ll ever meet. In this program they make it their mission to develop both your scientific and personal skills to prepare you for a career in science, medicine, or wherever your interests take you. My experience at the Broad has shaped me as a scientist and as a person, and I end this summer with a renewed motivation to pursue the questions surrounding life.Flavor is driven in part by both taste and smell, leading us to wonder if these preferences can be explained or are at least reflected by changes in the distribution of olfactory receptors in the main olfactory epithelium. To interpret changes in receptor distribution, it is also important to understand what ligands the receptors bind to. In order to explore this, we are developing an in vivo screening method in mice that will allow us to begin profiling which receptors interact with specific ligands. Our approach takes advantage of the well-established observation that only one of >1000 olfactory receptors are expressed in each sensory neuron of the main olfactory epithelium. After applying an olfactory stimulus, we first aim to sort out the nuclei of activated neurons by using fluorescent in situ hybridization (FISH) against an immediate early gene marker for activated neurons. We then aim to sequence the whole transcriptome of fluorescently sorted nuclei in order to identify the receptor expressed in that neuron. This method will allow us to begin understanding which receptors are responding to specific stimuli and if their distribution changes following perturbations in the mother.
Project: Developing tools for understanding the developing and remodeling of the olfactory epithelium
Mentor: Hattie Chung, Regev Lab