Dr. Arnav Moudgil from Stanford University Awarded $90,000 Knights Templar Eye Foundation Grant for Retinal Development Research
Dr. Arnav Moudgil from the Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California was awarded a $90,000 grant for the research entitled: 3D Genome Folding and Gene Regulation of Otx2 in Retinal Development.
All cells in the body share the same genome, yet this identical code gives rise to a diverse and distinct set of cell types, tissues, and organs. Genomes carefully control the order and timing by which specific genes are activated or silenced; how this process unfolds is a fundamental question in developmental genomics. At the end of retinal development, the gene Otx2 is required to from two different kinds of cells: bipolar interneurons and the light-sensitive photoreceptors. High levels of Otx2 lead to bipolar cells, while low Otx2 expression gives rise to photoreceptors. Otx2 is mis-expressed in congenital diseases such as oculo-auriculo-vertebral (Goldenhar) syndrome, as well as in retinoblastoma, a pediatric ocular tumor.
The three-dimensional folding of the genome is an additional regulator of gene expression, but understanding of this process is in its infancy. Folding patterns can bring certain genomic control sequences—termed enhancers—in contact with gene promoters to regulate their expression. The principles underlying these behaviors are an area of active investigation. Dr. Moudgil is using microscopy to visualize Otx2 folding during retinal development and to connect those structures to expression of Otx2. In addition to observing this during normal development, he will introduce targeted mutations to perturb this region of the genome and explore how these edits affect genome structure and transcription. Finally, Dr. Moudgil will synthesize his data into a computational model to understand the quantitative factors impacting expression. His efforts will help shed light on a dynamic yet necessary process for normal retinal development.