Mu Center for Botanical Interaction Studies

描述(申请人提供)：植物药能够同时与多个细胞调节途径相互作用。我们中心的目标是探索抗氧化剂相关途径之间的串扰。要研究的5个关键途径是(抗氧化)途径(Nrf2/Keap1和NADPH氧化酶)，以及它们与核因子-kappaB-、雌激素-和刺猬信号通路的相互作用。研究项目1：针对5个信号通路的植物制剂预防前列腺癌将测试5个单独的、广泛使用的植物膳食补充剂将通过5个关键信号通路预防前列腺癌的假设。研究项目2：植物酚对氧化/亚硝化信号通路的影响：对脑缺血的意义将检验这样一种假说，即植物通过调节NADPH氧化酶-、Nrf2/Keap1-和/或NF-kappaB-信号通路以及S-亚硝化修饰蛋白质来促进大脑健康和防止神经退行性变。研究项目3：抗氧化剂植物药和抗菌防御剂将测试具有强大抗氧化剂活性的植物化合物调节与抗菌防御剂相关的细胞事件的假设。该中心包括五个核心设施。行政核心将监督该中心的研究、培训和试点计划。核心A：植物学/植物基因组学核心将识别、培育和记录植物原材料，包括接骨木和大豆的新品种。核心B：营养/动物核心将提供转基因小鼠并为研究项目准备饲料。核心C：分析化学核心将为量化植物化合物及其代谢物和验证植物材料提供分析支持和质量控制。核心D：相互作用核心：Mega-sequencing/Proteomics/lnformatics/Nitrosylation)将为蛋白质组和亚硝化分析提供新技术，为信使核糖核酸分析提供DNA巨型测序，并通过生物信息学和统计支持进行数据整合。MU非常支持该中心，并提供资金培训和支持四名研究生研究助理。试点项目将有助于为新的植物学补助金提供种子资金，并允许新教师和新学生的职业发展。本中心采用生物信息学的方法，结合最新的先进的信使核糖核酸和蛋白质分析技术，同时探索5条信号通路，具有很强的创新性。这种类型的协同作用，当与中心研究人员的植物学和途径专业知识相结合时，将产生对人类健康重要的新信息。 公共卫生相关性：我们建议研究的植物药物已经被公众广泛使用，尽管它们具有抗氧化特性，可能提供癌症、免疫和神经保护作用，但这些作用的分子基础在很大程度上还不清楚。我们的总体目标是测试和识别植物药物和相关的分子机制，这些机制可以通过预防神经退行性疾病和传染病以及癌症来潜在地提供有益于维持身体和大脑健康的效果。

DESCRIPTION (provided by applicant): Botanicals are capable of interacting with several cell regulating pathways at the same time. Our Center's goal is to explore the crosstalk between antioxidant-related pathways. The 5 key pathways to be examined are the (anti)oxidant (Nrf2/Keap1 and NADPH oxidase) pathways and their interactions with the NF-kappaB-, estrogen-, and hedgehog-signaling pathways. Research Project 1: Botanicals Targeting 5 Signaling Pathways to Prevent Prostate Cancer will test the hypothesis that five individual, widely-used botanical dietary supplements will prevent prostate cancer through the five key signaling pathways. Research Proiect 2: Botanical Phenolics on Oxidative/Nitrosative Signaling Pathways: Implication for Cerebral Ischemia will test the hypothesis that botanicals promote brain health and prevent neurodegeneration through modulating the NADPH oxidase-, Nrf2/Keap1-, and/or NF-kappaB-signaling pathways, and protein modifications by S-nitrosylation. Research Project 3: Antioxidant Botanicals and Antimicrobial Defenses will test the hypothesis that botanical compounds that possess potent antioxidant activity modulate cellular events associated with antimicrobial defense. The Center includes five core facilities. The Administrative Core will oversee the Center's research, training, and pilot programs. Core A: Botanicals/Plant Genomics Core will identify, cultivate, and document raw plant materials including novel cultivars of elderberry and soy. Core B: Nutrition/Animal Core will provide transgenic mice and prepare diets for the research projects. Core C: Analytical Chemistry Core will provide analytical support and quality control for quantifying botanical compounds and their metabolites, and verifying plant material. Core D: Interactions Core: Mega-sequencing/Proteomics/lnformatics/Nitrosylation) will provide novel technology for proteomic and nitrosylation analyses, DNA mega-sequencing for mRNA analysis, and data integration through bioinformatics and statistical support. MU is highly supportive of this Center and is providing funds to train and support four graduate research assistants. Pilot projects will help provide seed money for new botanical grants and allow career development of both new faculty and students. Our Center's approach using bioinformatics to explore 5 signaling pathways concurrently by the latest cutting edge technology in mRNA and protein analysis is highly innovative. This type of synergism, when combined with the botanical and pathway expertise of Center investigators, will generate new information important in human health. PUBLIC HEALTH RELEVANCE: The botanicals we propose to study are already extensively used by the public, and though they have antioxidant properties that may offer cancer, immuno-, and neuroprotective effects, the molecular basis of these effects is largely not understood. Our overall goal is to test and identify botanicals and related molecular mechanisms that can potentially offer beneficial effects to maintain a healthy body and brain by preventing neurodegenerative and infectious diseases, as well as cancer.