Frances Imarhia, a junior majoring in biomedical engineering at Brown University, studied the underlying cellular changes that occur as a result of mutations in the genes TSC1 and TSC2 and how these changes can affect the pathology of Tuberous Sclerosis Complex.
Tuberous Sclerosis Complex (TSC) is a rare genetic disorder characterized by the growth of numerous benign tumors throughout the body. This disease also causes a wide spectrum of additional symptoms with varying levels of severity. TSC is caused by the mutation of the gene(s) TSC1 and/or TSC2. Participating in BSRP this summer has taught me how important it is for scientists to be resilient and flexible in the face of adversity. Although I didn’t expect to do computational work this summer, BSRP’s computational genomics course allowed me to obtain new skills and apply them to my knowledge of biology. As a result, I acquired the tools I will need to answer a wide variety of questions emerging in the biomedical field using existing data sets like the CCLE. I look forward to seeing how all the members of my cohort use this knowledge to foster advancement in future biomedical research.This mutation subsequently causes a disruption in the mTORC signaling pathway, an important regulator for cell proliferation, which leads to tumor formation. The disruption of the mTOR pathway is common in all cases of TSC but does not give an explanation for some other symptoms that can accompany TSC tumors. By comparing the gene expression in cells exhibiting mutations in TSC1/TSC2 to cells lacking these mutations, we aimed to gain a deeper understanding of the underlying impacts of TSC1/TSC2 mutation on the pathology of the disease. This could help us identify new ways to detect and treat TSC. After utilizing DESeq2 analysis, we found 1007 genes that showed a significant difference in expression as a result of TSC1 mutation. Additionally, we found 623 genes that showed a significant difference in expression as a result of TSC2 mutation. Then, through a GOSeq analysis, we found that these differentially expressed genes can be linked to significant changes in pathways affecting the development of the extracellular matrix and the immune system. Therefore, we can conclude that TSC can result in underlying changes to these cellular functions. Understanding these changes could be the key to predicting the pathology of TSC.
Project: The Effects of TSC1/TSC2 Mutations on Cellular Processes
Mentor: Christopher Vockley, Lander Lab (Gene Regulation)