Nuclear Receptors: Orphan Brothers

核受体：孤儿兄弟

• 批准号: 6733125
• 负责人: DAVID J MANGELSDORF
• 金额: $ 1.75万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-20 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6733125
• 关键词: meeting /conference /symposium; nuclear receptors; travel

DESCRIPTION (provided by applicant): Nuclear receptors belong to a highly conserved superfamily of transducers which play a key role in processing of extracellular signals into gene expression responses during development, differentiation, reproduction and integrated homeostasis of all vertebrates and many invertebrates. These receptors act as transcriptional regulators and respond to lipophilic ligands, such as steroid and thyroid hormones, retinoids, vitamin D, oxysterols, bile acids and certain fatty acids. The family also includes a number or orphan receptors for which biochemical functions are unknown and ligands are currently being sought. Because they regulate so many cellular functions, nuclear receptors are important and promising targets for drugs in numerous medical fields, including those of cancer, inflammation, endocrine and metabolic disorders, hypertension, and reproductive functions. The present challenges are first to elucidate how the structural organization of the diverse multiprotein-receptor complexes is related to the molecular mechanisms underlying transcriptional activation and repression of target genes, and second to integrate, at the organism level, the physiological processes and signal transduction pathways regulated through nuclear receptors with those controlled through cell membrane receptors. This meeting will bring together leading experts, as well as younger investigators and trainees in a manner that integrates the diverse aspects of nuclear receptor biology, encompassing three dimensional structure of multiprotein-receptor complexes, molecular mechanisms of action of nuclear receptors and their coregulators at their target genes, genetic dissection of receptor-mediated physiological functions during development and postnatal life through conditional somatic mutagenesis, identification of ligands and physiological roles for orphan receptors, ligand design, use of functional genomics to characterize receptor-regulated gene networks, and development of new technologies to aid in drug discovery.

描述（由申请人提供）： 核受体属于换能器的高度保守的超家族，在在发育，分化，繁殖和所有脊椎动物的发育，分化，繁殖和综合稳态过程中，在将细胞外信号处理为基因表达反应中起关键作用。这些受体充当转录调节剂，并对亲脂性配体有反应，例如类固醇和甲状腺激素，类维生素D，氧化霉素，氧甲醇，胆汁酸和某些脂肪酸。该家族还包括一个尚不清楚生化功能的数量或孤儿受体，目前正在寻求配体。由于它们调节了如此多的细胞功能，因此核受体是许多医学领域的药物（包括癌症，炎症，内分泌和代谢性疾病，高血压和生殖功能）的重要目标。目前的挑战首先是为了阐明多种多蛋白质受体复合物的结构组织如何与转录激活和靶基因抑制的基础机制有关，其次是在生物体水平，生理过程和通过核受体调节的核受体中整合的生物体水平和信号转导途径，这些途径通过核受体调节。这次会议将以整合核受体生物学的各个方面的方式，将领先的专家以及年轻的研究人员和年轻的研究者汇集在一起配体和生理作用，用于孤儿受体，配体设计，功能基因组学来表征受体调节的基因网络以及开发新技术以帮助药物发现。