New multidimensional separation tools for proteomics and biomarker discovery

蛋白质是生命的真正组成部分，具有多种功能，是体内最重要和最多样化的生物物种。 有成千上万种不同的蛋白质，每一种蛋白质都在执行其特定的功能，同时在一个健康的人身上保持着谨慎的平衡。 为了应对压力，药物，感染，青春期，疾病，伤害，怀孕和生活中的其他事件，身体改变蛋白质的类型和浓度，以更好地执行特定任务。 显然，识别和测量所有这些蛋白质对于促进我们对蛋白质及其相互作用如何驱动生命过程的理解至关重要。 为了回答蛋白质生物化学的基本问题，我们需要能够直接测量和表征复杂生物样品中蛋白质的分析工具。 为了实现这一目标，我们将设计、构建和评估一个能够解析和测量数千种蛋白质的多维分离系统。 与目前只能解析数百种蛋白质的系统相比，这将是一个巨大的进步。 我们将使用这个系统来绘制不同生物样本中存在的蛋白质，如尿液，羊水和血清。 与分离系统携手，我们将开发一种仪器，使我们能够从图谱中选择特定的蛋白质，并将它们分解成其组成部分进行鉴定。 结合使用这两个系统，我们将为生物样品产生全面的蛋白质浓度和鉴定数据。 更重要的是，这些技术将使我们能够测量和识别响应疾病，损伤或其他生理损伤的蛋白质。 这些结果将拓宽和加深我们对特定蛋白质在健康和疾病中的作用的理解。

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.