This summer, I’m interning at the Walsh Lab at Boston Children’s Hospital and Harvard University under the guidance of my mentor and principal investigator, Dr. Janet Song, conducting research on the genetic basis of human brain evolution. Following the evolutionary divergence of human and chimpanzee from their latest common ancestor, extensive genetic variation has accumulated across their genomes, spanning protein-coding regions, regulatory elements, and intergenic sequences. Our research aims to identify the categories of genetic variants with evolutionary significance through various alignment models. In addition, we are particularly interested in genetic variants contributing to the unique patterns of human brain development, such as the dramatic increase in brain size, enhanced cognitive complexity, and structural reorganization. We employ a tetraploid stem cell system, in which human and chimpanzee pluripotent stem cells are fused. This system allows us to examine species-specific genetic contribution to neurodevelopmental phenotypes at the molecular level.
During my summer internship, I’ll test different protocols for stem cell fusion and then construct various human-chimpanzee and other human-nonhuman primate tetraploid stem cell lines. I’ll get involved in single-cell RNA-Seq to analyze differential gene expression driven by human-specific genetic variants. Thus, in the upcoming weeks, I plan to develop proficiency in tissue culture and various cellular techniques by shadowing the lab members and through hands-on experiences of growing and maintaining stem cell lines and conducting cellular experiments. I’ll also learn scRNA-Seq, beginning with learning the standard computational workflow, replicating some pipelines, and gradually generating my own code. Finally, I hope to read more primary research literature in this field to deepen my understanding of human evolutionary genetics.