Eric Lu

MSTP in PhD Training

Program: Molecular Genetics and Genomics

Current advisor: Dave Pagliarini, PhD

Undergraduate university: University of Arizona, 2021

Enrollment year: 2021

Research summary
Systems-level characterization of elements of mitochondrial stress response pathways.

The ability to sense and respond to stressors in the ever-changing environment is one of the cornerstones of evolution and survival. As a result, there are many cellular mechanisms in place that buffer stress and protect every organism’s capacity to grown and reproduce despite changing or adverse conditions. There is a large body of literature that links a reduced capacity to sense and respond to stressors with a reduction in fitness, development of human disease, and ageing. Given this, it is unsurprising that mitochondria have multiple dedicated and specific stress-response pathways, given their central role in signaling, apoptosis, Ca2+ homeostasis, and of course, metabolism. A mitochondrial-specific stress response was first observed in C. elegans in which an accumulation of misfolded aggregated protein caused by a deletion of the OTC gene resulted in an upregulated transcriptional program similar to the one achieved by the unfolded protein response (UPR) in the endoplasmic reticulum (ER). This mitochondrial unfolded protein response (UPRmt) was eventually demonstrated to be unique from the response found in the ER. How mitochondrial distress is sensed and subsequently signaled to the nucleus to elicit an appropriate response currently remains an outstanding mystery. This past summer I worked in the lab of Dr. David Pagliarini to try to investigate the UPRmt from a systems-level approach and attempt to identify novel players in this intricate signaling network. I utilized a burgeoning forward genetic screen called Saturated Transposon Analysis in Yeast (SATAY) that features many distinct advantages over more traditional screening techniques such as random mutagenesis and deletion library screening. In addition to the screen, I also collected samples to conduct proteomic, lipidomic, and metabolomic profiling of these strains against a wild-type control to try to detect differences between the normal and stress-induced states. Understanding the differences between the profiles in the two states, combined with information about the genes that play a significant role in the pathway may yield new insights into the UPRmt.

Graduate publications