2010 Cold Spring Harbor Laboratory Conference on Systems Biology: Global Regulati

描述（由申请人提供）：该提案寻求NIH资助，以支持关于系统生物学方法的第七次科学会议，以了解真核生物中的基因调控。拟议的2010年会议将重点关注基因调节的五个关键方面--顺式调节逻辑、转录调节网络、核小体和表观遗传学、转录后调节以及调节网络的变异和进化。此外，一个会议将专门用于分析基因调控的新兴技术。2012年和2014年的会议将遵循类似的形式，并将包括与会议召开时的当前研究高度相关的议题。 细胞如何控制基因表达是生物学中的一个基本问题。自从发现基因和DNA的双链螺旋结构以来，人们一直在不断地研究这个问题。许多伟大的发现已经取得，包括核机器，使转录以及DNA序列，以控制基因表达。尽管有这些努力，我们对基因调控的分子机制的认识仍然是粗略的。例如，人类基因组中大多数基因的转录调控序列和调控蛋白仍然定义不清，尽管可以获得完整的基因组序列。现在，随着各种生物的基因组序列信息量迅速增长，这个问题变得更加紧迫。传统上，研究人员通过分析特定转录因子和/或控制单个基因表达模式的顺式调控元件的DNA结合偏好来研究基因调控。这些研究已经初步确定了大约100个转录因子的DNA序列基序，并导致了基因组水平的转录调控涉及模块化DNA序列元件（如增强子、沉默子、绝缘子和基础启动子元件）之间复杂的相互作用的想法。近几年来，新的基因组学方法在分析基因表达的每个步骤方面取得了迅速进展。这些方法中的许多方法在其设计或解释中涉及计算组件。其他策略是从几个完整的基因组序列的可用性和未来更多的前景发展而来的。其中包括分析密切相关物种之间的序列保守性，以检测非编码区的“系统发育足迹”，以及使用基因组微阵列和下一代测序技术研究DNA-蛋白质和RNA-蛋白质相互作用。这些新方法的结果为原核和真核细胞的基因调控过程提供了前所未有的细节。 很明显，实验和计算生物学家之间的有效合作将需要掌握基因调控的复杂问题。因此，我们建议举行一次会议，以便自由地跨学科交流现有的想法和专门知识。希望这次会议将提供一个建立新的合作机制，并讨论新的实验和计算方法的论坛。会议将于2010年3月23-27日在冷泉港实验室举行。已邀请22名国际知名人士作口头发言，另外将从申请人提交的会议摘要中选出大约45人。除了主题演讲，口头报告的长度为15'，5'用于提问和讨论。将包括海报会议，以鼓励非发言的与会者有意义的参与。此外，我们还将举办会前研讨会，让分子生物学家和生物信息学家熟悉了解彼此学科所需的关键概念、术语和缩略语。预计将有250-300名科学家出席会议。我们特别鼓励女科学家和初级研究人员参加-两名主旨发言人中有一名是女性，其余受邀发言人中有25%是女性，四名会议组织者中有两名是女性，前几年的大多数与会者都是学生、博士后或处于早期独立职业生涯的研究人员。 公共卫生相关性：自从发现基因和DNA的双链螺旋结构以来，一个中心问题就是这些基因在细胞中是如何打开和关闭的。几十年的研究已经对基因表达的基本机制有了深入的了解，近年来的努力已经转向了基因组如何一起打开或关闭。随着大量关于基因表达和基因组结构之间关系的生物学信息（DNA序列、DNA结构和修饰、染色质结构和修饰等）的涌现，各种不同的科学学科已经成为必要。生物学家和计算机科学家正在使用这些方法来阐明正常细胞状态下基因组编排的基本原理，以及全球调控如何在癌症等疾病状态下脱轨。这个两年一度的国际会议（2010年、2012年和2014年）将为这些科学家提供一个论坛，分享他们的最新发现，并将汇集该领域的顶尖专家。

DESCRIPTION (provided by applicant): This proposal seeks NIH funding to support the seventh in a series of scientific meetings on systems biology approaches to understanding gene regulation in eukaryotes. The proposed 2010 meeting will focus on five key aspects of gene regulation-cis-regulatory logic, transcriptional regulatory networks, nucleosomes and epigenetics, post-transcriptional regulation, and variation and evolution of regulatory networks. In addition, a session will be devoted to emerging technologies for analysis of gene regulation. The 2012 and 2014 meetings will follow a similar format and will include topics highly relevant to the current research at the time of the meeting. How cells control gene expression is a fundamental problem in biology. Ever since the discovery of the genes and the double strand helix structure of the DNA, there have been continuous investigations into this problem. Many great discoveries have been made, including the nuclear machineries that make transcripts as well as the DNA sequences that serve to control gene expression. Despite these efforts, our knowledge of the molecular mechanisms of gene regulation remains sketchy. For example, the transcriptional regulatory sequences and the regulatory proteins for most genes in the human genome are still poorly defined, despite the availability of the complete genome sequences. Now, with the amount of genome sequence information for various organisms rapidly growing, the problem has become ever more pressing. Traditionally, investigators have studied gene regulation by analyzing the DNA-binding preferences of specific transcription factors and/or the cis-regulatory elements that control the expression patterns of single genes. These studies have tentatively identified DNA sequence motifs for around one hundred transcription factors, and have led to the idea that transcriptional regulation at the genome level involves a complex interplay between modular DNA sequence elements such as enhancers, silencers, insulators, and basal promoter elements. The last several years have seen rapid advances in the development of new genomics approaches to analysis of each step of the gene expression. Many of these approaches involve a computational component in their design or interpretation. Other strategies have evolved from the availability of several complete genomic sequences and the prospects of many more to come. These include analyses of sequence conservation among closely related species to detect "phylogenetic footprints" in non-coding regions and the use of genomic microarrays and next-generation sequencing technologies to study DNA-protein and RNA-protein interactions. The results from these new approaches have provided unprecedented details on the gene regulatory processes in prokaryotic as well as eukaryotic cells. It is clear that effective collaborations between experimental and computational biologists will be required to come to grips with the complex problem of gene regulation. Thus we propose to conduct a meeting to permit a free cross-disciplinary exchange of existing ideas and expertise. It is hoped that this meeting will provide a mechanism for the establishment of new collaborations, and a forum for discussing new experimental and computational approaches. The meeting will be held at Cold Spring Harbor Laboratory on March 23-27, 2010. Twenty-two speakers of international renown have been invited to give oral presentations, and approximately forty-five others will be selected from submitted abstracts from applicants to the meeting. With the exception of the keynote address, oral presentations will be 15' in length with 5' for questions and discussions. Poster sessions will be included to encourage meaningful participation by the non-speaking attendees. In addition, we will hold pre-meeting workshops which will familiarize molecular biologists and bioinformaticians with the key concepts, terminology and acronyms needed to understand each others' disciplines. We expect attendance of approximately 250-300 scientists at the meeting. We particularly encourage female scientists and junior investigators to participate - one of the two keynote speakers, 25% of the remaining invited speakers, and two of the four meeting organizers are women, and the majority of the participants in previous years have been students, postdocs or investigators in their early independent career. PUBLIC HEALTH RELEVANCE: Ever since the discovery of genes and the double strand helix structure of the DNA, a central question has concerned how these genes are switched on and off in the cell. Decades of research have contributed to a robust understanding of the basic mechanisms of gene expression, and in recent years efforts have turned towards how sets of genes are turned on or off together. With the outpouring of enormous amounts of biological information about the relation between gene expression and genome architecture (DNA sequence, DNA structure and modification, chromatin structure and modification etc.), a variety of different scientific disciplines have become necessary. Biologists and computer scientists are using these approaches to shed light on the principles underlying the orchestration of sets of genes in normal cellular states and how global regulation can become derailed in disease states such as cancer. This biennial international conference (2010, 2012 and 2014) will provide a forum for these scientists to share their latest discoveries and will bring together the leading experts in the field.