About the JC Price Lab
The Price laboratory explores mechanisms used by living cells to control the quality and concentration of each molecule in the human body. The complexity of this task is really astounding. For example, there are ~20,000 different protein types in each cell. The quality and concentration of each one is carefully controlled in a condition generally referred to as protein homeostasis. When protein homeostasis fails, we quickly develop diseases like Alzheimer’s, diabetes, and cancer. Similar problems occur when the homeostasis of lipids or other metabolites fails. A big effort in our lab is developing the tools to study the processes supporting homeostasis in vivo and understand what changes as homeostasis is lost. Specifically, we use stable isotopes to label newly-synthesized molecules with a time-dependent tag. With a mass spectrometer, the time-dependent stable isotope enrichment and relative concentration of many molecules can be measured even within a complex mixture. This allows us to calculate synthesis and degradation rates simultaneously for many molecules in the body as it responds to stimuli. This allows us to perform experiments that survey broad sections of the proteome, and compare against DNA, RNA, or small molecules produced by enzymes within the cell. We have successfully used this technique in many different biosynthetic systems from "cell free" environments to humans. Currently, we are focused on understanding post-transcriptional control of the proteome composition within cells, especially on the changes associated with aging or disease as well as how protein degradation is regulated to maintain homeostasis. We also have projects quantifying lipid homeostasis to assess protein activity and monitoring structural stability to understand folding efficiency.
Protein structure determines function. As our bodies age, dysregulation of folding in the body leads to the buildup of misfolded proteins in amyloid plaques. These plaques are toxic and contribute to many diseases such as Alzheimer's, Parkinson's, and Amyloidosis. Despite the central role of folding in age and disease, little is actually known about how or why proteins misfold. In the Folding Group of the JC Price lab, we utilize the Iodine Protein Stability Assay (IPSA) to measure how stable proteins in the body fold. IPSA works by chemically unfolding proteins in differing amounts and labeling exposed amino acids with iodine. We then use mass spectrometry to quantify how much iodine is bound to each protein. From these iodine incorporation experiments, we use our software, CHalf, to generate folding curves and calculate "C½ values" which represent how much energy it takes to unfold a portion of the protein.