Biomolecular Interaction Networks: Function and Disease

生物分子相互作用网络：功能与疾病

• 批准号: 7804831
• 负责人: ANDREW D ROBERTSON
• 金额: $ 0.8万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804831
• 关键词: Binding; Biochemical; Biology; Canada; Cancer Diagnostics; Cell physiology; Complex; Data; Disease; Epigenetic Process; Event; Gene Dosage; Gene Expression Regulation; Gene Proteins; Genes; Genetic; Genetic Polymorphism; Genomics; Homeostasis; Individual; Knowledge; Lead; Malignant Neoplasms; Molecular; Multiple Partners; Mutation; Normal Cell; Nucleic Acids; Nucleotides; Organism; Play; Process; Property; Proteins; Proteomics; Regulatory Pathway; Research Personnel; Role; Seeds; Signal Transduction; Site; Therapeutic; Translational Regulation; base; combinatorial; human disease; in vivo; meetings; novel strategies; protein function; public health relevance; symposium; tool; transcription factor

DESCRIPTION (provided by applicant): This proposal is to request support for a Keystone Symposia meeting entitled Biomolecular Interaction Networks: Function and Disease, organized by Anna R. Panchenko, Teresa Przytycka and Andrea Califano, which will be held in Quibec, Canada from March 7 - 12, 2010. The function of proteins, nucleic acids, and other biomolecules can only be defined through their interactions in vivo. Such biochemical interactions - including those involved in signal transduction, transcriptional and translational regulation, as well as in the assembly of large molecular complexes - are astonishing in their magnitude and diversity. For instance, it has been shown that most proteins interact with multiple partners, forming intricate interaction networks. Similarly, an individual transcription factor can bind to tens of thousands of genomic sites and regulate the expression of thousands of genes, both in isolation and in combinatorial fashion. Regulatory interactions play a key role in determining cellular differentiation, in maintaining cellular and organism homeostasis, and in triggering abnormal differentiation events leading to human disease including cancer. Not surprisingly, even slight genetic and epigenetic perturbations of these regulatory pathways can trigger macroscopic changes in normal cell physiology and lead to disease. Due to the abundance of experimental data, researchers are starting to uncover some general rules and principles underlying molecular interaction networks: their topological properties, the relationships between their components, evolutionary conservation and divergence, and their role in maintaining specific cellular functions and processes. Despite significant advances, however, knowledge about the distinct functional roles of many proteins is still elusive. Thus, interaction networks have emerged as exceedingly useful tools in predicting context-specific molecular function based on knowledge of upstream regulators, cognate binding partners, and downstream regulated targets. Furthermore, molecular interaction networks are starting to provide a unique integrative context to study additional disease-related genetic and epigenetic data, including single nucleotide mutations and polymorphisms, gene copy number alterations and complex, polygenic diseases. PUBLIC HEALTH RELEVANCE: Despite significant advances in the fields of genomics and proteomics, knowledge about the distinct functional roles of many proteins and genes still remains elusive. The aim of this symposium is to bring together researchers from different fields of computational and experimental biology, genomics and proteomics, to discuss the use of biomolecular interaction networks to study cell function and human diseases. The topics discussed at the meeting will seed new approaches in gene and protein functional annotation, gene regulation and anti-cancer diagnostics and therapeutics.

描述(由申请人提供)：本提案请求支持由Anna R.Panchenko、Teresa Przytycka和Andrea Califano组织的题为生物分子相互作用网络：功能和疾病的Keystone研讨会，该会议将于2010年3月7-12日在加拿大魁北克举行。蛋白质、核酸和其他生物分子的功能只能通过它们在体内的相互作用来定义。这种生化相互作用--包括信号转导、转录和翻译调节，以及大分子复合体的组装--在规模和多样性上令人惊讶。例如，已有研究表明，大多数蛋白质与多个伙伴相互作用，形成复杂的相互作用网络。同样，一个单独的转录因子可以结合数万个基因组位置，并以隔离和组合的方式调节数千个基因的表达。 调控相互作用在决定细胞分化、维持细胞和生物体内环境平衡以及触发导致包括癌症在内的人类疾病的异常分化事件中起着关键作用。毫不奇怪，即使这些调控通路的轻微遗传和表观遗传扰动也会引发正常细胞生理的宏观变化，并导致疾病。由于大量的实验数据，研究人员开始揭示分子相互作用网络背后的一些一般规律和原理：它们的拓扑性质，它们组成部分之间的关系，进化的守恒和分歧，以及它们在维持特定细胞功能和过程中的作用。 然而，尽管取得了重大进展，关于许多蛋白质的不同功能作用的知识仍然难以捉摸。因此，相互作用网络已经成为非常有用的工具，可以基于上游调控因子、同源结合伙伴和下游调控靶标的知识来预测上下文特定的分子功能。此外，分子相互作用网络开始提供一个独特的综合背景来研究更多与疾病相关的遗传和表观遗传学数据，包括单核苷酸突变和多态、基因拷贝数改变和复杂的多基因疾病。 公共卫生相关性：尽管基因组学和蛋白质组学领域取得了重大进展，但对许多蛋白质和基因的不同功能作用的了解仍然难以捉摸。这次研讨会的目的是聚集来自计算和实验生物学、基因组学和蛋白质组学不同领域的研究人员，讨论利用生物分子相互作用网络来研究细胞功能和人类疾病。会议讨论的主题将为基因和蛋白质功能注释、基因调控以及抗癌诊断和治疗提供新的方法。