The Neal lab will examine the quality control mechanism that allows cells to clear away potentially toxic misfolded proteins. Many proteins are synthesized in a subcellular compartment called the endoplasmic reticulum (ER). Here, newly made proteins begin to fold into the structures they must adopt to be functional. Proteins that fold incorrectly are removed from the ER and degraded, to avoid the accumulation of protein aggregates that can irreparably damage the cell. As a postdoctoral fellow, I discovered a highly conserved protein from the rhomboid superfamily, Dfm1, that plays a critical role in extracting misfolded membrane proteins from the ER. Now, using techniques in yeast cell and molecular genetics, my lab will screen for parts of the rhomboid protein that are crucial for its activity and identify any partners with which it interacts. Concurrently, we are developing human cells and zebrafish as a model for complete characterization of similar rhomboid proteins involved in removing aberrant proteins. Because the accumulation of misfolded proteins is a hallmark of many human maladies—including cancer, neurodegenerative disease, and aging—our work could have broad-ranging therapeutic value.