Core--Functional genomics

核心--功能基因组学

• 批准号: 7052511
• 负责人: Sally A. Amundson
• 金额: $ 37.22万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052511
• 关键词: biomedical equipment development; biomedical facility; biotechnology; bioterrorism /chemical warfare; clinical research; cooperative study; environmental stressor; experimental designs; functional /structural genomics; gene expression; gene expression profiling; high throughput technology; human subject; radiation dosage; training

It is now well established that exposure of human cells to environmental stresses, including ionizing radiation, activates multiple signal transduction pathways, resulting in complex patterns of gene expression change. Expression of specific genes can be both dose- and stress- dependent, making gene expression profiling a potentially informative approach for much-needed radiation biodosimetry. Several issues remain to be resolved, however, including variations in baseline and treated expression levels among the population, potential confounding effects, and identification of an optimally informative gene set. Circulating lymphocytes represent a sensitive target for early radiation injury, highly responsive in terms of induced gene expression changes, and relatively easily biopsied. Peripheral blood cells will therefore be our primary model for development of a gene expression biodosirneter for radiation exposure. This Core will 1) establish and refine gene expression signatures diagnostic of human radiation exposure and dose in support of Project 2, 2) assess gene expression in parallel with micronuclei (Project 1) and patient urinary metabolomics (Project 3) to enable direct comparisons of biodosimetric techniques, and 3) provide a resource for oversight of experimental design pertaining to functional genomics and training of staff in support of Project 3 and the Pilot Projects as needed. By allowing measurement of gene expression changes across virtually the entire genome in a single experiment, the modern long oligonucleotide microarray approach is not only an efficient screen for potentially informative radiation biomarkers, but may also provide insight into the mechanistic basis of the human response to early radiation injury. Such information may suggest refinements of other biodosimetry techniques, and facilitate future collaborations between the Center for High-Throughput Minimally-Invasive Radiation Biodosimetry and the other Centers for Medical Countermeasures against Radiation, for instance by suggesting "druggable targets" and opportunities for development of chemoprotective intervention strategies.

现在已经很好地确定，人类细胞暴露于环境应力（包括电离辐射）会激活多个信号转导途径，从而导致基因表达变化的复杂模式。特定基因的表达既可以是剂量和胁迫依赖性的，从而使基因表达分析成为急需的辐射生物测量法的潜在信息方法。但是，仍然有几个问题要解决，包括基线和人群中的表达水平的变化，潜在的混杂效应以及对最佳信息基因集的识别。循环淋巴细胞代表了早期辐射损伤的敏感靶标，在诱导的基因表达变化方面高度响应，并且相对容易进行活检。因此，外周血细胞将是我们开发基因表达生物核能进行辐射暴露的主要模型。该核心将1）建立和完善基因表达特征的诊断人类辐射暴露 并剂量支持项目2，2）与微核（项目1）和患者尿尿代谢组学（项目3）并行评估基因表达，以直接比较生物量学技术，以及3）提供了一种资源，提供了与功能基因组学和Project 3 and Protot Project Suppers Project and Project and Project and Project and Project of Project and Project and Project of Project a的实验设计有关的资源。 通过在单个实验中允许几乎整个基因组的基因表达变化，现代的长寡核苷酸微阵列方法不仅是有效的潜在信息辐射生物标志物的有效筛选，而且还可以深入了解人类对早期辐射损伤反应的机械基础。这些信息可能暗示了其他生物测量技术的改进，并促进了高通量微侵入性辐射生物测量法与其他针对辐射的医学对策中心之间的未来合作，例如，提出“吸毒目标”和化学保护干预策略的发展机会。