Effect of E3 Ubiquitin Ligase TRIM11 on TDP-43 Aggregation

Students

College

Faculty

Professor of Cancer Biology

Project Summary

Through the Penn Undergraduate Research Mentorship program, I was lucky enough to spend my summer working in the Yang Lab with Dr. Shivani Ghaisas in the Department of Cancer Biology at the Perelman School of Medicine. Because I had never worked in a laboratory previously, this was an excellent opportunity for me to get exposed to a professional research environment. At the beginning of the summer, I became familiar with basic laboratory techniques and practices. I was taught many skills, including how to do cell culture work, transform bacteria, isolate plasmids, and run western blots. Likewise, I got familiar with handling mice and grew to be proficient with weaning, tagging, sexing, genotyping, and running behavioral tests on these animals. As I became more comfortable with the skills that I had learned and acquired more knowledge about the work done in the Yang lab, I was able to be more involved in the project that I would eventually complete. 

My project this summer focused on the effect of TRIM11, an E3 ubiquitin ligase, on TDP-43 aggregation in mouse models. The basis of this project was determined based on a hallmark characteristic of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease, being the aggregation of TDP-43 protein within motor neurons. The Yang lab has found that tripartite motif (TRIM) family proteins are involved in protein quality control and that TRIM11 identifies and promotes the degradation of misfolded proteins, which may be valuable for protecting against neurodegeneration. For my project, I conducted behavioral tests on mice that were injected with TRIM11 and on mice that were injected with GFP to see if TRIM11 could have therapeutic potential. The mice used were of the TDP-43 Q331K strain, which shows phenotypic characteristics and pathology of ALS observed in humans. I found that in many of the motor coordination tests, TRIM11 groups performed worse than those injected with GFP. Because of this, we concluded that TRIM11 most likely has a small therapeutic window and that titers beyond this margin would likely cause adverse effects in the TDP-43 Q331K mice. This project provides an understanding of how TRIM11 may be better used as a therapeutic treatment in the future.

Overall, I had a gratifying experience working in the Yang Lab this summer. I plan to continue working in the lab throughout the school year and hope to become more involved with projects in the future as I continue to learn more. I am very grateful for this opportunity and would like to thank Dr. Ghaisas, Dr. Yang, and PURM for making this possible.