Sidney Martin, a junior biology & chemistry double major at the University of Alabama in Huntsville, studied the effects of TSC1 and TSC2 mutations in the Cancer Cell Line Encyclopedia and how these changes can affect the pathology of Tuberous Sclerosis Complex.
Tuberous sclerosis complex (TSC) is a rare disease characterized by the growth of numerous noncancerous tumors in many parts of the body, especially in vital organs like the brain, heart, kidney, lung, and skin. Being in BSRP has taught me about the importance of community within the scientific realm. With a virtual setting, it was unknown if we were going to connect as a cohort. With a blend of computational and wet lab research background, our cohort tackled adversity as one. We relied on each other, trusted each other, and overcame obstacles while learning how to deal with imposter syndrome, how to become a leader, and how to talk about science to people who are in STEM and people who aren’t. Throughout this experience, we have built an everlasting bond that can’t be broken. As we go back to our respective institutions and beyond, I can’t wait to see the amazing things that my cohort will do. TSC is caused by mutations within the gene(s) TSC1 and TSC2. These mutations cause a disruption in the mTOR pathway which leads to excess cell division and cell proliferation. Because there are no TSC patient or cell line data, the Cancer Cell Line Encyclopedia (CCLE) was used because it contains over 1000 immortalized cancer cell lines including gene expression and mutation data. With this database, we hope to deepen our understanding of the TSC1/2 mutations. After using DESeq2 analysis to find significantly differentially expressed genes in TSC1 and TSC2, we used GOSeq to take those genes from the DESeq2 analysis to formulate a gene ontology so we can understand what biological processes are involved with these mutations. We found that mutations in TSC1 can be linked to pathways affecting the immune response and blood clotting while mutations in TSC2 can be linked to pathways affecting antigen processing, an immune response that is specific for producing antibodies. Connecting this with literature involving TSC patients with a TSC1 mutation, this data shows that we can potentially use the CCLE to study Tuberous Sclerosis. These findings could be the key to predicting the pathology of TSC.
Project: Using TSC1/2 mutations to study Tuberculosis Sclerosis Complex through the Cancer Cell Line Encyclopedia
Mentor: Brian Chamberlain, Group Leader in Medicinal Chemistry, Center for the Development of Therapeutics (CDoT)