Arundhati Natesan '21

Major: Integrative Neuroscience
Bio: Arundhati Natesan was born in India and grew up in Indonesia, before moving to the U.S. to study Cell & Molecular Neuroscience. She conducted research under the guidance of Dr. Kristina Dobrindt at Icahn School of Medicine at Mount Sinai. She hopes to pursue a PhD after graduation.

Title of Research: Genome editing of schizophrenia risk variant in hiPSCs
Mentor: Dr. Martin Di Grandi
Abstract: In the growing field of genetic studies, researchers continue to discover genetic risk factors for neuropsychiatric disorders. Human induced pluripotent stem cells, or hiPSCs, have allowed scientists to create and manipulate cell types from patients, enabling them to model human disorders in order to study their underlying mechanisms. The use of hiPSCs can be integrated with CRISPR-editing to control the genetic variation of cell lines. This technique allows the insertion, deletion, or modification of genetic material at targeted regions. Genome editing of the schizophrenia risk variant rs4702 in hiPSCs allow us to analyze its effect in combination with different host genomes. To exclude unwanted mutations, potential off-target regions for each gRNA were identified and specific primers were designed for the top potential off-target regions. The DNA of hiPSC clones from different editing experiments were analyzed by amplifying the four off-target regions most likely to be affected. Further research will involve the use of these generated hiPSC-derived and CRISPR-edited cell clones to create neurons to observe potential differences in their functionality depending on the risk variant and genomic background.