DESCRIPTION (provided by applicant): How cells control the expression of their genomes is a fundamental problem in biology. How the coordinate regulation of gene expression is affected by changes in the cellular and organismal environment is another fundamental question. Ever since the discovery that genes are encoded in the sequence of nucleotides that comprise the double strand DNA helix, there have been continuous investigations into these problems. The nuclear machineries that make transcripts as well as the many types of DNA sequences that serve to control gene expression have been discovered. Despite these efforts, many fundamental issues associated with the global regulation of gene expression remain unresolved. For example, the transcriptional regulatory sequences and the regulatory proteins for most genes in the human genome are still poorly defined. We cannot yet predict a gene's expression pattern from the sequence of its surrounding regulatory DNA or the pattern of nearby epigenetic marks, or how these are affected by environmental change. Nor, in the majority of cases, can we make rational alterations to the DNA that result in specific, predefined changes in expression. It is clear that effective collaborations between experimental and computational biologists will be required to come to grips with the complex problems of gene regulation. Thus we propose to host meetings that foster the free cross-disciplinary exchange of existing ideas and expertise. It is hoped that these meetings will provide a mechanism for the establishment of new collaborations, and a forum for discussing new experimental and computational approaches. This proposal seeks National Institutes of Health (NHGRI and NIEHS) funding to support the active participation of young scientists (graduate students, postdoctoral fellows and new faculty) in a continuing series of scientific meetings on systems biology, which have previously been held at Cold Spring Harbor Laboratory (CSHL) and in Puerto Rico. The conferences will be managed by CSHL and alternate yearly between the CSHL campus and a carefully selected offsite location in Puerto Rico. These meetings are intended to foster cross-disciplinary exchange of ideas and expertise between experimentalists and computational biologists interested in the organization and control of complex transcription networks in eukaryotes. The proposed meeting will focus on several key themes: Transcriptional Regulatory Networks; Cis- Regulatory Logic; Chromatin & Epigenetics; Post-transcriptional Regulation; Variation & Evolution; Emerging Technologies; Developmental Networks & Cellular Responses. Oral presentations will be given by a group of distinguished invited speakers as well as speakers selected from submitted abstracts. Selected speakers will include graduate students, postdoctoral fellows and junior faculty aiming for maximal inclusion of young investigators. Of special importance are the two poster sessions, where many participants can present their work in an atmosphere conducive to informal discussion. The meeting will be of moderate size and we expect about 250-300 people to attend, the vast majority of whom will be presenting a poster or talk. In years when the meeting is held offsite we will engage the participation of local scientists from the academic community in Puerto Rico. This proposal seeks funding to support the participation of early career investigators in this important meeting.

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 and pathological cellular states. This international conference will provide a forum for these scientists to share their latest discoveries and will bring together the leading experts in the field. The application specifically seeks support for the active participation of ealy career investigators at this conference.