Grant Dominic
Pronouns: He/Him/His
Research Mentor(s): Ming Li
Co-Presenter:
Research Mentor School/College/Department: MCDB / LSA
Presentation Date: April 20
Presentation Type: Poster
Session: Session 3 – 1:40pm – 2:30 pm
Room: League Ballroom
Authors: Grant Dominic, Liang Chen
Presenter: 80
Abstract
The lysosome is an essential organelle which functions as a key agent in the recycling of macromolecules and maintenance of cellular homeostasis. Failures of lysosomal function can play key parts in lysosomal storage disorders and neurodegenerative diseases. An important factor to the lysosome’s function within the cell is lysosomal biogenesis – the process by which more lysosomes are created if needed. Traditionally, it is understood that under certain conditions, including nutrient deficiency and oxidative stress, lysosomal biogenesis can be induced by translocation of Transcription Factor EB (TFEB) and TFE3 (members of the MiTF family) to the nucleus. Translocation of this manner is caused by the inactivation of protein kinase MTORC1, which under unstressed conditions would have phosphorylated TFEB, thereby keeping the transcription factor out of the nucleus. However, the phenotype of lysosomal biogenesis can also be observed upon the knockout of the gene TMEM 251. Using the CRISPR-Cas9 system, we further knocked out the genes coding for TFEB, TFE3, and STAT3 from TMEM 251 KO cell lines, as well as a TFEB/TFE3 double knockout. Using flow cytometry analysis to measure the number of acidic compartments (primarily lysosomes) within our cell lines, we observed that none of our transcription factor knockouts could return lysosome count to the basal level. This indicates that the pathway through which the knockout of TMEM 251 induces lysosome biogenesis is independent from the transcription factors listed above, and is instead a novel and unexplored pathway.
Interdisciplinary, Natural/Life Sciences
