New multidimensional separation tools for proteomics and biomarker discovery

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Proteins, the veritable building blocks of life, perform a multitude of functions and are the most important and diverse biological species in the body. There are tens of thousands of different proteins, each performing its specialized function while being held in careful balance in a healthy person. In response to stress, drugs, infection, puberty, disease, injury, pregnancy and other events in life, the body alters the types and concentrations of proteins to better perform specific tasks. Clearly, identifying and measuring all these proteins is critical to advancing our understanding of how proteins, and their interactions, drive the life process. To answer fundamental questions of protein biochemistry, we need analytical tools that can directly measure and characterize proteins from complex biological samples. To accomplish this, we will design, build and evaluate a multidimensional separation system capable of resolving and measuring thousands of proteins. Compared to current systems that can only resolve hundreds of proteins, this will be a huge step forward. We will use this system to map the proteins present in diverse biological samples such as urine, amniotic fluid and serum. Hand-in-hand with the separation system we will develop an instrument that will allow us to select specific proteins from the map and break them down into their component pieces for identification. Using these two systems together we will produce comprehensive protein concentration and identification data for the biological samples. More importantly, these technologies will allow us to measure and identify the proteins that change in response to disease, injury or other physiological insults. These results will broaden and deepen our understanding of the roles of specific proteins in health and disease.