NanoSystems Biology Cancer Center

描述（由申请人提供）：系统生物学研究所开创的生物学和医学的系统方法有望在未来2-15年内改变肿瘤学的实践，将其从反应性学科（在患者生病后做出反应）转变为预测，预防和个性化模式。 这将部分通过使用血液作为健康和疾病的窗口来实现。 这个想法是，生物学是由蛋白质和其他分子网络介导的，这些蛋白质和其他分子在细胞内通过调节基因表达来执行正常功能。 在疾病中，这些网络中的一个或多个受到干扰（遗传或环境），基因表达模式的改变介导了疾病。 这些受疾病干扰的网络随着疾病的进展而动态变化，它们的基因表达模式也是如此。 我们通过计算分析确定了前列腺和卵巢中的器官特异性转录本，并再次通过计算分析确定了其中一些转录本似乎是分泌的。 我们的假设是，这些分子中至少有一些以可检测的水平分泌到血液中，因此构成了每个器官的分子指纹，这些器官的蛋白质组分随着从正常状态转变为疾病状态以及随着疾病状态的进展而在其表达水平上单独变化。 这些器官特异性血液标记物的力量在于，它们可以让人们专注于单个器官中发生的变化，并且血液可以浸泡所有器官和组织，因此可以从每个器官和组织中获得分泌的蛋白质指纹。 因此，我们计划检验这一假设，即这些血液指纹成为一个多参数的蛋白质组，能够识别特定的疾病和这些疾病的进展状态，并将使用血液蛋白质组学技术对三种不同的癌症：前列腺癌，卵巢癌和胶质母细胞瘤。 我们还将测试这些血液测试将允许在非常早期的阶段发现癌症的想法。 未来需要将这些血液诊断技术扩展到数百万患者，这意味着必须开发新的测量技术，这些技术最终能够进行大约1000次定量蛋白质测量，并且在非常小的样品上快速，廉价和全自动地进行。 因此，在这项资助中，我们也将开始开发使用微流体和纳米技术方法的血液蛋白测量装置，这些方法将开始获得这些功能。

DESCRIPTION (provided by the applicant): The systems approach to biology and medicine pioneered by the Institute for Systems Biology promises to transform the practice of oncology over the next 2-15 years moving it from a reactive discipline (responding after the patient is sick) to a predictive, preventive and personalize modes. This will be, in part, achieved by using the blood as a window into health and disease. The idea is that biology is mediated by networks of proteins and other molecules that operate within the cell to execute normal functions through the regulation of gene expression. In disease, one or more of these networks becomes perturbed (genetically or environmentally) and the altered patterns of gene expression mediate the disease. These disease-perturbed networks change dynamically with the progression of the diseases, as do their patterns of gene expression. We have identified by computational analyses organ-specific transcripts in the prostate and ovary and again by computational analyses some of these appear to be secreted. Our hypothesis is that at least some of these molecules are secreted into the blood at detectable levels and hence constitute a molecular fingerprint for each organ whose protein components change individually in their levels of expression as one shifts from the normal to a diseased state and as one progresses through the disease state. The power of these proposed organ-specific blood markers is that they let one focus on the changes that occur in just a single organ and that the blood baths all organs and tissues and hence receives secreted protein fingerprints from each. Hence we plan to test the hypothesis that these blood fingerprints become a multiparameter panel of proteins capable of identifying particular diseases and the state of progression of these diseases-and will do using blood proteomics techniques for three different cancers: prostate, ovarian and glioblastoma. We will also test the idea that these blood tests will allow cancer to be detected at a very early stage. The need to extend these blood diagnostic techniques in the future to millions of patients means that new measuring techniques will have to be developed which are ultimately capable of making perhaps 1000 quantitative protein measurements-and doing so rapidly, cheaply, on very small samples and fully automatically. Hence in this grant we will also begin to develop blood-protein measuring devices using microfluidic and nanotechnology approaches that will begin to acquire these features.