Maria Lysandrou

Maria Lysandrou, a junior neuroscience major at the University of Chicago, analyzed spatial distribution of olfactory receptors.

The olfactory epithelium is comprised of 10 million sensory neurons that each express 1 of 1000 unique olfactory receptors (ORs).

At the Broad, I was able to work on cutting-edge research with world-leading scientists. I learned how to become a better scientific communicator, as well as how to ask and answer questions independently. I am so thankful for my mentor and the Broad community for being so supportive in my path to becoming a scientist. This experience has not only given me lifelong relationships, but also the foundation and tools for success in graduate school. These receptors bind and detect chemicals, resulting in our sense of smell. These sensory neurons are constantly replenished by stem cells that reside throughout the entire epithelium. Previous work using in situ hybridization to profile RNA expression of a subset of receptors has shown that receptor expression is often spatially confined, such that each receptor is expressed in a specific zone of the olfactory epithelium. Furthermore, it is unknown whether stem cells regenerating sensory neurons differ across zones that predispose receptor choice. To systematically quantify the spatial expression of ORs across sensory neurons, stem cells, and other cell types, we applied Slide-seq, a novel spatial transcriptomics method, to measure how gene expression changes across the olfactory epithelium. We first assigned a cell type to each Slide-seq bead to map genes that are highly variable due to cell-type differences independent of space. We do this by projecting the cell types identified with 10X, a higher depth droplet-sequencing-based single-cell method, onto the beads of the Slide-seq data. We then found genes that are highly variable across space in the epithelium, within each cell type. Next, we quantified the spatial dispersion of each OR across sensory neurons using Shannon entropy to ask whether some receptors were more spatially confined than others. By systematically quantifying how genes vary in their expression spatially in multiple cell types, we aim to identify novel candidates that are involved in the spatial regulation of receptor expression.

Project: Analyzing spatial distribution of olfactory receptors with Slide-seq

Mentor: Hattie Chung, Regev Lab