Identifying How T Cells Utilize Branched-Chain Amino Acids (BCAAs) To Activate mTORC1 or Engage Downstream Mitochondrial Metabol

Rajat Ramesh




Project Summary

LARS is an aminoacyl tRNA synthetase used to attach leucine, an essential (branching) amino acid, to tRNA. It has also been discovered that, using leucine, LARS communicates with a complex called mTOR, which deals with cell translation and growth by coordination with a myriad of bodily factors. Worldwide, there are around 10 cases where a specific mutation in a LARS gene is causing severe immune dysfunction in patients. Therefore, narrowing down on what particular LARS mutation is causing these effects and moving towards a solution is a crucial area of research. For that reason, we spent ten weeks in the Bailis Laboratory studying how a leucylated LARS complex affects mTOR activation in T cells, as previous research only indicates that this phenomenon occurs in a mutant kidney cell line 293T. We also took this project a step further and studied how glucose can affect the efficacy of communication between LARS and mTOR in T cells, as it has implications in branching chain amino acid (BCAA) degradation. Through this research experience, we both learned how to utilize many new pieces of lab equipment, mastered several complicated lab protocols, and significantly improved our knowledge of many lab techniques and practices. At the lab, we came across and got to attempt the genotyping of mouse DNA, the intricacy of qPCR, cDNA creation, gel electrophoresis, cell culture, amongst many other assays. Outside of the technical skills, we also learned many soft skills, like how to give information yet succinct lab presentations and how to keep neat and organized lab notebooks to track our work over the summer. Working in the Bailis Lab truly gave us a chance to explore the depths and breadth of immunology research. Prior to this lab experience, neither of us had a thorough lab background, coupled with the fact that we missed the experience of being in a lab during our fully remote freshman year due to the COVID-19 pandemic. So, the seamless and exciting introduction to lab endeavors that we received from this PURM experience was a truly priceless adventure that will greatly boost us forward in our academic and social careers.

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