Studies of Materials with Physiological Properties

具有生理特性的材料的研究

基本信息

批准号：
8289615
负责人：
STUART L SCHREIBER
金额：
$ 55.68万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8289615
关键词：
Address Affect Antibodies Biological Assay Biological Process Biology Cells Chemistry Chromatin Clinical Trials Complex Disease Elements Enzymes Gene Expression Glucose Glutamine Grant HDAC6 gene Histones Human Inositol Language Life Measurement Mediating Mediator of activation protein Medical Medicine Metabolic Methods Microfluidics Mus Names Nutrient Pathway interactions Physiological Plasma Cells Polyphosphates Process Property Reagent Research Role Screening procedure Signal Transduction Sirolimus Stress Synthesis Chemistry Techniques Variant base design follow-up graduate student high throughput screening histone methyltransferase human FRAP1 protein improved inhibitor/antagonist innovation mTOR Inhibitor new therapeutic target novel public health relevance research study response small molecule tubacin

Address Affect Antibodies Biological Assay Biological Process Biology Cells Chemistry Chromatin Clinical Trials Complex Disease Elements Enzymes Gene Expression Glucose Glutamine Grant HDAC6 gene Histones Human Inositol Language Life Measurement Mediating Mediator of activation protein Medical Medicine Metabolic Methods Microfluidics Mus Names Nutrient Pathway interactions Physiological Plasma Cells Polyphosphates Process Property Reagent Research Role Screening procedure Signal Transduction Sirolimus Stress Synthesis Chemistry Techniques Variant base design follow-up graduate student high throughput screening histone methyltransferase human FRAP1 protein improved inhibitor/antagonist innovation mTOR Inhibitor new therapeutic target novel public health relevance research study response small molecule tubacin

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项目摘要

DESCRIPTION (provided by applicant): This project aims to discover small-molecule probes of both mTOR-dependent nutrient-response signaling and histone-mark-dependent chromatin signaling. These probes are expected to illuminate the principles that underlie the nutrient-response and chromatin-signaling cellular networks, and to provide starting points for the discovery of new medicines that act on these networks. These aims will be pursued by the use of (1) global metabolic measurements of cells treated with an mTOR inhibitor, (2) chromatin-state-selective antibodies identified by the use of a new microfluidic/microarray-based technique for screening antibodies, (3) novel high-content screens and gene expression/high-throughput screens for the identification of small- molecule modulators of chromatin-modifying enzymes, and (4) both a novel synthetic chemistry method for targeting small molecules towards chromatin-modifying enzymes and follow-up synthetic chemistry to optimize the properties of the small-molecule probes. Lay language: Recent clinical trials, some successfully completed and others still ongoing, suggest that small molecules that target either of two only recently recognized cellular pathways (one named "nutrient- response" and the other "chromatin") have remarkable potential as life-saving medicines. The recognition of these pathways was made possible by previous research sponsored by this grant. The proposed continuation research aims to discover new small molecules that target new elements of these pathways and to perform experiments that will illuminate their most promising medical applications. PUBLIC HEALTH RELEVANCE The proposed research aims to address the gap between understanding and affecting disease by innovating in chemistry and exploring complex biology with small molecules. The research aims to discover small molecules that modulate two biological processes - stress signaling and chromatin signaling - with considerable promise for medicine. Such small molecules will be used to probe the consequences of modulating key mediators of the processes in order to gain a better understanding of their medical potential as targets for novel therapeutics.

描述（由申请人提供）：该项目旨在发现MTOR依赖性营养响应信号传导和组蛋白依赖性染色质信号传导的小分子探针。预计这些探针将阐明营养素反应和染色质信号细胞网络的原理，并为发现在这些网络上起作用的新药物提供起点。通过使用（1）使用MTOR抑制剂处理的细胞的全球代谢测量值，（2）通过使用新的基于微流体/微阵列的技术来筛选新型高位筛选型号的较小的型号识别，（3）鉴定较小的型号的较小的摩尔群岛，该抗体识别（3）染色质修饰酶和（4）一种新型的合成化学方法，用于将小分子靶向染色质修饰酶和随访的合成化学，以优化小分子探针的性质。外行语言：最近的临床试验，有些成功完成，另一些仍在进行中，这表明针对两种最近才识别出的两个细胞途径中的一个小分子（一种被称为“营养 - 反应”，另一种称为“染色质”）具有巨大的潜力作为挽救生命的药物。这笔赠款赞助的先前研究使这些途径的认可成为可能。拟议的延续研究旨在发现针对这些途径新元素的新小分子，并进行实验，以阐明其最有前途的医疗应用。公共卫生相关性拟议的研究旨在通过化学创新并用小分子探索复杂的生物学来解决理解和影响疾病之间的差距。该研究旨在发现调节两个生物学过程的小分子 - 应力信号传导和染色质信号 - 具有相当多的医学有望。这样的小分子将用于探测调节过程中关键介体的后果，以便更好地了解其医疗潜力作为新型治疗剂的靶标。