Source: CORNELL UNIVERSITY submitted to NRP
FUNCTIONAL ORGANIZATION OF BIOMOLECULAR NETWORKS
Sponsoring Institution
Agricultural Research Service/USDA
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0408020
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
May 24, 2004
Project End Date
May 23, 2009
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853
Performing Department
(N/A)
Non Technical Summary
(N/A)
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
2011460108034%
2011549108033%
2011530108033%
Goals / Objectives
The broad aim of this project is to investigate the functional organization of regulatory and signaling networks in bacterial cells, that is, to understanding the information processing embedded within biomolecular networks, with a particular focus on processes of gene regulation in the bacterial plant pathogen Pseudomonas syringae. The proposed research will endeavor to uncover aspects of distributed functionality, specificity, and control by developing models of regulatory and signaling processes at various scales of resolution, and incorporating ideas and techniques from molecular and cell biology, computer science, computational science, statistical mechanics, biochemistry, dynamical systems, and complex systems. Close interaction with the emerging experimental capabilities of the USDA-ARS P. syringae systems biology group will lead to analyses and models of regulatory networks, through the examination of data describing sigma factor-DNA interactions, gene and protein expression, mutant phenotypes, and transcription factor binding sites.
Project Methods
Methods motivated by statistical physics, computer science, and complex systems theory will be used to identify putative regulatory motifs in the genome of Pseudomonas syringae. Collections of regulatory sequences upstream of coordinately regulated transcription units in experimental datasets (e.g., microarrays, promoter trap libraries, and transposon mediated mutagenesis screens with reporter systems) will be used to define putative regulons and infer transcription-level gene regulation networks. Molecular mechanisms underlying information processing and control will be related to functional redundancies and compensation, distributed control and specificity of recognition, signal transduction, and interplay with metabolic pathways. The kinematic and dynamic aspects of gene regulation networks will be studied using computational and mathematical methods as sufficient experimental time-series data become available.

Progress 10/01/08 to 09/30/09

Outputs
Progress Report Objectives (from AD-416) The broad aim of this project is to investigate the functional organization of regulatory and signaling networks in bacterial cells, that is, to understanding the information processing embedded within biomolecular networks, with a particular focus on processes of gene regulation in the bacterial plant pathogen Pseudomonas syringae. The proposed research will endeavor to uncover aspects of distributed functionality, specificity, and control by developing models of regulatory and signaling processes at various scales of resolution, and incorporating ideas and techniques from molecular and cell biology, computer science, computational science, statistical mechanics, biochemistry, dynamical systems, and complex systems. Close interaction with the emerging experimental capabilities of the USDA-ARS P. syringae systems biology group will lead to analyses and models of regulatory networks, through the examination of data describing sigma factor-DNA interactions, gene and protein expression, mutant phenotypes, and transcription factor binding sites. Approach (from AD-416) Methods motivated by statistical physics, computer science, and complex systems theory will be used to identify putative regulatory motifs in the genome of Pseudomonas syringae. Collections of regulatory sequences upstream of coordinately regulated transcription units in experimental datasets (e.g., microarrays, promoter trap libraries, and transposon mediated mutagenesis screens with reporter systems) will be used to define putative regulons and infer transcription-level gene regulation networks. Molecular mechanisms underlying information processing and control will be related to functional redundancies and compensation, distributed control and specificity of recognition, signal transduction, and interplay with metabolic pathways. The kinematic and dynamic aspects of gene regulation networks will be studied using computational and mathematical methods as sufficient experimental time-series data become available. Significant Activities that Support Special Target Populations Research conducted under this agreement was monitored by weekly meetings between the ADODR and the cooperator. The major accomplishments in this reporting period include (a) continued development of computational models of specific regulatory motifs from various experimental and genomic datasets, (b) investigation of small RNA target detection algorithms and models of small RNA-mediated kinetic networks, and (c) theoretical and computational investigation of robustness and crosstalk in biological networks. The agreement terminated May 23, 2009.

Impacts
(N/A)

Publications


    Progress 05/24/04 to 05/23/09

    Outputs
    Progress Report Objectives (from AD-416) The broad aim of this project is to investigate the functional organization of regulatory and signaling networks in bacterial cells, that is, to understanding the information processing embedded within biomolecular networks, with a particular focus on processes of gene regulation in the bacterial plant pathogen Pseudomonas syringae. The proposed research will endeavor to uncover aspects of distributed functionality, specificity, and control by developing models of regulatory and signaling processes at various scales of resolution, and incorporating ideas and techniques from molecular and cell biology, computer science, computational science, statistical mechanics, biochemistry, dynamical systems, and complex systems. Close interaction with the emerging experimental capabilities of the USDA-ARS P. syringae systems biology group will lead to analyses and models of regulatory networks, through the examination of data describing sigma factor-DNA interactions, gene and protein expression, mutant phenotypes, and transcription factor binding sites. Approach (from AD-416) Methods motivated by statistical physics, computer science, and complex systems theory will be used to identify putative regulatory motifs in the genome of Pseudomonas syringae. Collections of regulatory sequences upstream of coordinately regulated transcription units in experimental datasets (e.g., microarrays, promoter trap libraries, and transposon mediated mutagenesis screens with reporter systems) will be used to define putative regulons and infer transcription-level gene regulation networks. Molecular mechanisms underlying information processing and control will be related to functional redundancies and compensation, distributed control and specificity of recognition, signal transduction, and interplay with metabolic pathways. The kinematic and dynamic aspects of gene regulation networks will be studied using computational and mathematical methods as sufficient experimental time-series data become available. Significant Activities that Support Special Target Populations Research conducted under this agreement was monitored by weekly meetings between the ADODR and the cooperator. The major accomplishments in this reporting period include development of (a) comparative genomics methodologies for producing high-resolution maps of core and variable (strain-specific) genomic regions and, (b) computational methods to associate specific regulatory motifs with sets of coordinately expressed genes identified via time-course microarray experiments. The research addresses the Action Plan for National Program 303: Plant Diseases, Component 2: Biology, Ecology, Epidemiology and Spread of Plant Pathogens and Their Relationships with Hosts and Vectors and Problem Statement 2A: Pathogen Biology, Virulence Determinants and Genetics of the Pathogen.

    Impacts
    (N/A)

    Publications


      Progress 10/01/06 to 09/30/07

      Outputs
      Progress Report Objectives (from AD-416) The broad aim of this project is to investigate the functional organization of regulatory and signaling networks in bacterial cells, that is, to understanding the information processing embedded within biomolecular networks, with a particular focus on processes of gene regulation in the bacterial plant pathogen Pseudomonas syringae. The proposed research will endeavor to uncover aspects of distributed functionality, specificity, and control by developing models of regulatory and signaling processes at various scales of resolution, and incorporating ideas and techniques from molecular and cell biology, computer science, computational science, statistical mechanics, biochemistry, dynamical systems, and complex systems. Close interaction with the emerging experimental capabilities of the USDA-ARS P. syringae systems biology group will lead to analyses and models of regulatory networks, through the examination of data describing sigma factor-DNA interactions, gene and protein expression, mutant phenotypes, and transcription factor binding sites. Approach (from AD-416) Methods motivated by statistical physics, computer science, and complex systems theory will be used to identify putative regulatory motifs in the genome of Pseudomonas syringae. Collections of regulatory sequences upstream of coordinately regulated transcription units in experimental datasets (e.g., microarrays, promoter trap libraries, and transposon mediated mutagenesis screens with reporter systems) will be used to define putative regulons and infer transcription-level gene regulation networks. Molecular mechanisms underlying information processing and control will be related to functional redundancies and compensation, distributed control and specificity of recognition, signal transduction, and interplay with metabolic pathways. The kinematic and dynamic aspects of gene regulation networks will be studied using computational and mathematical methods as sufficient experimental time-series data become available. Significant Activities that Support Special Target Populations This report serves to document research conducted under a Specific Cooperative Agreement between ARS and the Theory Center, recently reorganized as the Center for Advanced Computing, at Cornell University. Additional details can be found in the report for the in-house associated project 1907-21000-027-00D, �Pseudomonas syringae Systems Biology�. Research conducted under this agreement was monitored by weekly meetings between the ADODR and the cooperator. The major accomplishments in this reporting period are (a) the development of comprehensive statistical methods for the segmentation of bacterial genomes to identify �backbone regions� shared amongst similar strains and strain-specific regions which may reflect novel virulence or fitness factors. (b), analysis of protein binding sites involved in iron-dependent gene expression. (c), development of a methodology for summarizing phylogenetic distribution of genes in fully-sequenced bacterial genomes.

      Impacts
      (N/A)

      Publications


        Progress 10/01/05 to 09/30/06

        Outputs
        Progress Report 4d Progress report. This report serves to document research conducted under a Specific Cooperative Agreement between ARS and the Theory Center at Cornell University. Additional details of research can be found in the report for the parent 1907-21000-017-00D, "Computational Models for Gene Control Networks in Pseudomonas Syringae". The cooperator for this project is Dr. Christopher Myers. The major accomplishments in this reporting period are the development of a computation model for binding sites for the ferric uptake regulator and PvdS-dependent promoters.

        Impacts
        (N/A)

        Publications


          Progress 10/01/04 to 09/30/05

          Outputs
          4d Progress report. This report serves to document research conducted under a Specific Cooperative Agreement between ARS and the Theory Center at Cornell University. Additional details of research can be found in the report for the parent CRIS 1907-21000-017-00D, Computational Models for Gene Control Networks in Pseudomonas Syringae. This agreement was initiated in May 2004. The major accomplishments in this reporting period are: (a) the identification of the HrpL-dependent promoter based on microarray and RT-PCR results; (b) identification of putative sigma-70 (RpoD)-dependent promoters based on proteomics data; (c) development of a comprehensive modeling infrastructure for gene regulation problems.

          Impacts
          (N/A)

          Publications


            Progress 10/01/03 to 09/30/04

            Outputs
            4. What were the most significant accomplishments this past year? D. Progress Report: This report serves to document research conducted under a Specific Cooperative Agreement between ARS and the Theory Center at Cornell University entitled "Functional Organization of Biomolecular Networks". Additional details of research can be found in the report for the parent CRIS 21000-017-00D, "Computational Models for Gene Control Networks in Pseudomonas Syringae". This agreement was initiated in May 2004. The major accomplishment for this reporting period is the application of Gibbs sampling methods to identifying hrp boxes and other candidate regulatory motifs in intergenic sequences upstream of genes observed to be differentially regulated in microarray experiments.

            Impacts
            (N/A)

            Publications