Multidimensional Separation Tools for Proteomics and Methods to Determine Metabolic Capacity

蛋白质是名副其实的生命构件，具有多种功能，是体内最重要、最多样的生物物种。有成千上万种不同的蛋白质，每一种都发挥着自己的特殊功能，同时在健康人体内保持着谨慎的平衡。为了应对生活中的压力、药物、感染、青春期、疾病、伤害、怀孕和其他事件，身体会改变蛋白质的类型和浓度，以更好地执行特定的任务。显然，识别和测量所有这些蛋白质对于推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的蛋白质的分析工具。这项提议有两个主要的研究途径。首先，我们提出建立一个能够分辨和测量数千种蛋白质的多维分离系统。与目前只能分解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定位存在于不同生物样本中的蛋白质，如尿液、羊水和血清。与分离系统携手合作，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的多肽进行鉴定。

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 biochemistry, we need analytical tools that can directly measure and characterize proteins from complex biological samples. This proposal has two main avenues of research. In the first, we propose building 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 peptides for identification.